Patent Law Weblog

recent posts

about

  • Myriad Genetics Files Suit Against Ambry Genetics for Genetic Diagnostic Testing of BRCA Genes

    By
    Kevin E. Noonan —

    MyriadToday
    Myriad Genetics sued Ambry Genetics, Corp. in the District of Utah, Central Division
    for patent infringement of ten patents relating to genetic diagnostic testing
    (Case No. 2:13-cv-00640-RJS; complaint).  Ambry
    Genetics was one of the first companies to announce that it would provide genetic diagnostic testing for the BRCA 1 and BRCA 2
    genes on the day the U.S. Supreme Court announced its decision in AMP v. Myriad Genetics on the question
    of "whether human genes are patentable."  Joining Myriad as plaintiffs are the
    University of Utah Research Foundation, the Trustees of the University of
    Pennsylvania, HSC Research and Development Limited Partnership, and
    Endorecherche Inc.

    The
    Complaint alleges that:

    Defendant began offering its
    BRCA1 and BRCA2 analysis as part of its cancer testing menu on June 13, 2013.  On information and belief, Defendant offers stand-alone tests comprising full
    gene sequencing and deletion/duplication analyses for the BRCA 1 and BRCA 2
    genes.  On information and belief, Defendant also offers full gene sequencing
    and deletion/duplication analyses for the BRCA 1 and BRCA 2 genes as part of
    multiple hereditary cancer panels that test cancer susceptibility using
    next-generation sequencing technology.

    Defendant is infringing,
    contributing to the infringement of, and/or inducing others to infringe the '999
    patent by making, manufacturing, promoting, marketing, advertising, distributing,
    offering for sale and selling and/or causing to be offered or sold certain
    BRCA1, BRCA2, BRCAPlus, BreastNext, OvaNext, and CancerNext products that
    infringe at least the following claim of [each of the patents in suit]
    literally and/or under the doctrine of equivalents for ten patents owned or
    licensed to Myriad.

    The
    specific claims Myriad alleges are infringed include the following:

    First
    Claim for Relief:  U.S. Patent No.
    5,709,999

    Claim 6: A method for detecting a
    germline alteration in a BRCA1 gene, said alteration selected from the group
    consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human
    which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human
    sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human
    sample with the proviso that said germline alteration is not a deletion of 4
    nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1, wherein a
    germline alteration is detected by amplifying all or part of a BRCA1 gene in
    said sample using a set of primers specific for a wild-type BRCA1 gene to
    produce amplified BRCA1 nucleic acids and sequencing the amplified BRCA1
    nucleic acids.

    Second
    Claim for Relief: U.S. Patent No. 5,747,282

    Claim 6: An
    isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino
    acid sequence set forth in SEQ ID NO:2, 
    wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1,
    and having at least 15 nucleotides of the DNA of claim 2.

    Claim 16: A pair
    of single-stranded DNA primers for determination of a nucleotide sequence of a
    BRCA1 gene by a polymerase chin reaction, the sequence of said primers being
    derived from human chromosome 17q, wherein the use of said primers in a
    polymerase chain reaction results in the synthesis of DNA having all or part of
    the sequence of the BRCA1 gene.

    Claim 17: The
    pair of primers of claim 16 wherein said BRCA1 gene has the nucleotide sequence
    set forth in SEQ ID NO:1.

    Third Claim for Relief: U.S. Patent No. 5,753,441

    Claim 7: A method
    for screening germline of a human subject for an alteration of a BRCA1 gene
    which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a
    tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from
    said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1
    RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1
    gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
    alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
    sequence is compared by hybridizing a BRCA1 gene probe which specifically
    hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and
    detecting the presence of a hybridization product wherein a presence of said
    product indicates the presence of said allele in the subject.

    Claim 8: A method
    for screening germline of a human subject for an alteration of a BRCA1 gene
    which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a
    tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from
    said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1
    RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1
    gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
    alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
    sequence is compared by amplifying all or part of a BRCA1 gene from said sample
    using a set of primers to produce amplified nucleic acids and sequencing the
    amplified nucleic acid.

    Claim 12: A
    method for screening germline of a human subject for an alteration of a BRCA1
    gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA
    from a tissue sample from said subject or a sequence of BRCA1 cDNA made from
    mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type
    BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the
    BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
    alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
    sequence is compared by amplifying BRCA1 nucleic acids from said sample to
    produce amplified nucleic acids, hybridizing the amplified nucleic acids to a
    BRCA1 DNA probe specific for a BRCA1 allele and detecting the presence of a
    hybridization product, wherein the presence of said product indicates the
    presence of said allele in the subject.

    Claim 23. A
    method for detecting a germline alteration in a BRCA1 gene, said alteration
    selected from the group consisting of the alterations set forth in Tables 11
    and 12 which comprises analyzing a sequence of the BRCA1 gene or BRCA1 RNA from
    a human sample or analyzing the sequence of BRCA1 CDNA made from mRNA from said
    sample, wherein a germline alteration is detected by amplifying all or part of
    a BRCA1 gene in said sample using a set of primers to produce amplified nucleic
    acids and sequencing the amplified nucleic acids.

    Claim 26.  A method for detecting a germline alteration
    in a BRCA1 gene, said alteration selected from the group consisting of the
    alterations set forth in Tables 11 and 12 which comprises analyzing a sequence
    of the BRCA1 gene or BRCA1 RNA from a human sample or analyzing the sequence of
    BRCA1 CDNA made from mRNA from said sample, wherein a germline alteration is
    detected by amplifying BRCA1 gene nucleic acids in said sample, hybridizing the
    amplified nucleic acids to a BRCA1 DNA probe specific for one of said
    alterations and detecting the presence of a hybridization product, wherein the
    presence of said product indicates the presence of said alteration.

    Fourth Claim for Relief: U.S. Patent No. 5,837,492

    Claim 29. A pair
    of single-stranded DNA primers of at least 15 nucleotides in length for
    determination of the nucleotide sequence of a BRCA2 gene by a polymerase chain
    reaction, the sequence of said primers being isolated from human chromosome 13,
    wherein the use of said primers in a polymerase chain reaction results in the
    synthesis of DNA comprising all or at least 15 contiguous nucleotides of the
    BRCA2 gene.

    Claim 30. The
    pair of primers of claim 29 wherein said BRCA2 gene has the nucleotide sequence
    set forth in SEQ ID NO:1.

    Fifth Claim for Relief: U.S. Patent No. 6,033,857

    Claim 4. A method
    for diagnosing a predisposition for breast cancer in a human subject which
    comprises comparing the germline sequence of the BRCA2 gene or the sequence of
    its mRNA in a tissue sample from said subject with the germline sequence of the
    wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the
    germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject
    indicates a predisposition to said cancer, wherein the detection in the
    alteration in the germline sequence is determined by an assay selected from the
    group consisting of (a) observing shifts in electrophoretic mobility of single-stranded
    DNA on non-denaturing polyacrylamide gels, (b) hybridizing a BRCA2 gene probe
    to genomic DNA isolated from said tissue sample, (c) hybridizing an
    allele-specific probe to genomic DNA of the tissue sample, (d) amplifying all
    or part of the BRCA2 gene from said tissue sample to produce an amplified
    sequence and sequencing the amplified sequence, (e) amplifying all or part of
    the BRCA2 gene from said tissue sample using primers for a specific BRCA2
    mutant allele, (f) molecularly cloning all or part of the BRCA2 gene from said
    tissue sample to produce a cloned sequence and sequencing the cloned sequence,
    (g) identifying a mismatch between (1) a BRCA2 gene or a BRCA2 mRNA isolated
    from said tissue sample, and (2) a nucleic acid probe complementary to the
    human wild-type BRCA2 gene sequence, when molecules (1) and (2) are hybridized
    to each other to form a duplex, (h) amplification of BRCA2 gene sequences in
    said tissue sample and hybridization of the amplified sequences to nucleic acid
    probes which comprise wild-type BRCA2 gene sequences, (i) amplification of
    BRCA2 gene sequences in said tissue sample and hybridization of the amplified
    sequences to nucleic acid probes which comprise mutant BRCA2 gene sequences,
    (j) screening for a deletion mutation in said tissue sample, (k) screening for
    a point mutation in said tissue sample, (l) screening for an insertion mutation
    in said tissue sample, (m) in situ hybridization of the BRCA2 gene of said
    tissue sample with nucleic acid probes which comprise the BRCA2 gene.

    Sixth Claim for Relief: U.S. Patent No. 5,654,155

    Claim 2. A method
    of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
    associated with breast or ovarian cancer comprising:
        a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        b) sequencing said amplified fragment by dideoxy
    sequencing;
        c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        d) comparing the sequence of said amplified DNA to
    the sequence of SEQ. ID. NO: 1;
        e) determining the presence or absence of each of
    the following polymorphic variations in said individual's BRCA1 coding
    sequence:
        AGC and ACT at position 2201, TTG and CTG at
    position 2430,  CCG and CTG at position
    2731,  GAA and GGA at position 3232, AAA
    and AGA at position 3667, TCT and TCC at position 4427, and ACT and GGT at
    position 4956;
        f) determining any sequence differences between
    said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 wherein the
    presence of any of the said polymorphic variations and the absence of a
    polymorphism outside of positions 2201, 2430, 2731, 3232, 3667, 4427, and 4956,
    is correlated with an absence of increased genetic susceptibility to breast or
    ovarian cancer resulting from a BRCA1 mutation in the BRCA1 coding sequence.

    Claim 3. A method
    according to claim 2 wherein said oligonucleotide primer is labeled with a
    radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
    label or an enzyme label

    Claim 4. A method
    of detecting an increased genetic susceptibility to breast and ovarian cancer
    in an individual resulting from the presence of a mutation in the BRCA1 coding
    sequence, comprising:
        a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        b) sequencing said amplified fragment by dideoxy
    sequencing;
        c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        d) comparing the sequence of said amplified DNA to
    the sequence of SEQ. ID. NO: 1;
        e) determining any sequence differences between
    said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 to determine the
    presence or absence of polymorphisms in said individual's BRCA coding sequences
    wherein a polymorphism which is not any of the following:
        AGC or AGT at position 2201, TTG or CTG at position
    2430, CCG or CTG at position 2731, GAA or GGA at position 3232, AAA or AGA at
    position 3667, TCT or TCC at position 4427, and AGT or GGT at position 4956;
        is correlated with the potential of increased
    genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
    mutation in the BRCA1 coding sequence.

    Seventh Claim for Relief: U.S. Patent No. 5,750,400

    Claim 2. A method
    of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
    associated with ovarian or breast cancer disease, comprising:
        (a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        (b) sequencing said amplified DNA fragment by
    dideoxy sequencing;
        (c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        (d) comparing the sequence of said amplified DNA
    fragment to a BRCA1(omi) DNA sequence selected from the group
    consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
    with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
    together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
    NO: 5;
        (e) determining the presence or absence of each of
    the following polymorphic variations in said individual's BRCA1 coding
    sequence:
            (i) C and T at position 2201,
            (ii) T and C at position 2430,
            (iii) C and T at position 2731,
            (iv) A and G at position 3232,
            (v) A and G at position 3667,
            (vi) T and C at position 4427, and
            (vii) A and G at position 4956;
        (f) determining any sequence differences between
    said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
    sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
    ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
    SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
    5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
    variations and the absence of a variation outside of positions 2201, 2430,
    2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
    genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
    mutation in the BRCA1 coding sequence.

    Claim 3. A method
    of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
    associated with ovarian or breast cancer disease, comprising:
        (a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        (b) sequencing said amplified DNA fragment by
    dideoxy sequencing;
        (c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        (d) comparing the sequence of said amplified DNA
    fragment to a BRCA1(omi)) DNA sequence selected from the group
    consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
    with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
    together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
    NO: 5;
        (e) determining the presence or absence of each of
    the following polymorphic variations in said individual's BRCA1 coding
    sequence:
            (i) C and T at position 2201,
            (ii) T and C at position 2430,
            (iii) C an d T at position 2731,
            (iv) A and G at position 3232,
            (v) A and G at position 3667,
            (vi) T and C at position 4427, and
            (vii) A and G at position 4956; and
        (f) determining any sequence differences between
    said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
    sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
    ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
    SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
    5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
    variations and the absence of a variation outside of positions 2201, 2430,
    2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
    genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
    mutation in the BRCA1 coding sequence;
        wherein codon variations occur at the following
    frequencies, respectively, in a Caucasian population of individuals with no
    family history of breast or ovarian cancer:
            (i) at position 2201, C and T occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (ii) at position 2430, T and C occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (iii) at position 2731, C and T occur at
    frequencies from about 25 to about 35%, and from about 65 to about 75%,
    respectively;
            (iv) at position 3232, A and G occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (v) at position 3667, A and G occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (vi) at position 4427, T and C occur at frequencies
    from about 45 to about 55%, and from about 45 to about 55%, respectively; and
            (vii) at position 4956, A and G occur at
    frequencies from about 35 to about 45%, and from about 55 to about 65%,
    respectively.

    Claim 4. A method
    according to claims 2 or 3, wherein said oligonucleotide primer is labeled with
    a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
    label, or an enzyme label.

    Claim 5. A method
    of detecting an increased genetic susceptibility to breast and ovarian cancer
    in an individual resulting from the presence of a mutation in the BRCA1 coding
    sequence, comprising:
        (a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        (b) sequencing said amplified DNA fragment by
    dideoxy sequencing;
        (c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        (d) comparing the sequence of said amplified DNA
    fragment to a BRCA1(omi) DNA sequence selected from the group
    consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
    with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
    together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
    NO: 5;
        (e) determining any sequence differences between
    said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
    sequence selected from the group consisting of: SEQ. ID. NO.: 1 together with
    SEQ ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together
    with SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID
    NO: 5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or
    absence of base changes in said individual's BRCA1 coding sequence wherein a
    base change which is not any one of the following:
            (i) C and T at position 2201,
            (ii) T and C at position 2430,
            (iii) C and T at position 2731,
            (iv) A and G at position 3232,
            (v) A and G at position 3667,
            (vi) T and C at position 4427, and
            (vii) A and G at position 4956, is correlated with
    the potential of increased genetic susceptibility to breast or ovarian cancer
    resulting from a BRCA1 mutation in the BRCA1 coding sequence.

    Claim 6. A method
    of detecting an increased genetic susceptibility to breast and ovarian cancer
    in an individual resulting from the presence of a mutation in the BRCA1 coding
    sequence, comprising:
        (a) amplifying a DNA fragment of an individual's
    BRCA1 coding sequence using an oligonucleotide primer which specifically
    hybridizes to sequences within the gene;
        (b) sequencing said amplified DNA fragment by
    dideoxy sequencing;
        (c) repeating steps (a) and (b) until said
    individual's BRCA1 coding sequence is completely sequenced;
        (d) comparing the sequence of said amplified DNA
    fragment to a BRCA1(omi) DNA sequence selected from the group
    consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
    with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
    together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
    NO: 5;
        (e) determining any sequence differences between
    said individual's BRCA1 coding sequences and a BRCA1(omi) DNA
    sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
    ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
    SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
    5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or absence
    of base changes in said individual's BRCA1 coding sequence wherein a base
    change which is not any one of the following:
            (i) C and T at position 2201,
            (ii) T and C at position 2430,
            (iii) C and T at position 2731,
            (iv) A and G at position 3232,
            (v) A and G at position 3667,
            (vi) T and C at position 4427, and
            (vii) A and G at position 4956, is correlated with
    the potential of increased genetic susceptibility to breast or ovarian cancer
    resulting from a BRCA1 mutation in the BRCA1 coding sequence, wherein codon
    variations occur at the following frequencies, respectively, in a Caucasian
    population of individuals with no family history of breast or ovarian cancer:
            (i) at position 2201, C and T occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (ii) at position 2430, T and C occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (iii) at position 2731, C and T occur at
    frequencies from about 25 to about 35%, and from about 65 to about 75%,
    respectively;
            (iv) at position 3232, A and G occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (v) at position 3667, A and G occur at frequencies
    from about 35 to about 45%, and from about 55 to about 65%, respectively;
            (vi) at position 4427, T and C occur at frequencies
    from about 45 to about 55%, and from about 45 to about 55%, respectively; and
            (vii) at position 4956, A and G occur at
    frequencies from about 35 to about 45%, and from about 55 to about 65%,
    respectively.

    Claim 7. A method
    according to claims 5 or 6, wherein said oligonucleotide primer is labeled with
    a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
    label, or an enzyme label.

    Eighth Claim for Relief: U.S. Patent No. 6,051,379

    Claim 32. A
    method of detecting a predisposition or higher susceptibility to cancer in an
    individual, comprising:
        (a) digesting DNA from an individual to obtain DNA
    fragments;
        (b) separating said DNA fragments;
        (c) detecting a DNA fragment containing nucleotide
    number 2192, 3772, 5193, 5374, 6495 or 6909 of the BRCA2 gene sequence or a
    sequence variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909 of
    the BRCA2 gene sequence by sequencing;
        (d) comparing the sequence of said fragment with
    the BRCA2 gene sequence to determine the presence or absence of a sequence
    variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909, wherein
    the presence of a sequence variation indicates a predisposition or higher
    susceptibility to cancer.

    Claim 33. A
    method according to claim 32 further comprising amplifying said DNA fragments
    prior to the detecting step (c).

    Ninth Claim for Relief: U.S. Patent No. 6,951,721

    Claim 5. A method
    for determining an omi haplotype of a human BRCA1 gene comprising: (a)
    determining the nucleotide sequence of the BRCA1 gene or fragment thereof from
    at least one female individual with a family history which indicates a
    predisposition to breast cancer, (b) comparing the determined nucleotide
    sequence from said female individual to SEQ ID NO: 263, and (c) determining the
    presence of the following nucleotide variations: thymine at nucleotides 2201
    and 2731, cytosine at nucleotides 2430 and 4427, and guanine at nucleotides
    3232, 3667 and 4956, wherein the presence of the nucleotide variations in the
    determined nucleotide sequence indicates the omi1 haplotype,  further comprising comparing the determined
    nucleotide sequence to SEQ ID NO: 265.

    Tenth Claim for Relief: U.S. Patent No. 7,250,497

    Claims 3, 4, 5, 6, 7, 8, 11, 14, 17, 18, 19

    [Claim 1. An isolated
    nucleic acid comprising SEQ ID NO:6, and the complement thereof.

    Claim 2. The isolated nucleic acid of claim 1, wherein
    said isolated nucleic acid comprises SEQ ID NO:37, or the complement thereof.]

    Claim 3. A method of making the isolated nucleic
    acid of claim 2 comprising amplifying genomic DNA isolated from a sample
    obtained from a human patient.

    Claim 4. A method of making the isolated nucleic
    acid of claim 1 comprising amplifying genomic DNA isolated from a sample
    obtained from a human patient.

    Claim 5. The method of claim 4, wherein said sample
    is a blood sample.

    Claim 6. The method of claim 4, wherein said
    amplification is by the polymerase chain reaction.

    Claim 7. The method of claim 4, wherein said
    patient is being evaluated for an enhanced risk of cancer.

    Claim 8. The method of claim 4, wherein said cancer
    is breast or ovarian cancer.

    Claim 11. A method of making the isolated nucleic
    acid of claim 9 comprising amplifying genomic DNA isolated from a sample
    obtained from a human patient.

    Claim 14. A method of making the isolated nucleic
    acid of claim 12 comprising amplifying genomic DNA isolated from a sample
    obtained from a human patient.

    Claim 17. A method of making the isolated nucleic
    acid of claim 15 comprising amplifying genomic DNA isolated from a sample
    obtained from a human patient.

    Claim 18. The isolated nucleic acid of claim 1,
    wherein said isolated nucleic acid comprises SEQ ID NO:41, or the complement
    thereof.

    Claim 19. A
    method of making the isolated nucleic acid of claim 18 comprising amplifying
    genomic DNA isolated from a sample obtained from a human patient.

    These method claims differ from the claims
    invalidated by the District Court in the Myriad
    case and affirmed by the Federal Circuit, which recited as limitations merely "comparing"
    an individual's BRCA gene sequence with the "normal" one, and thus
    Myriad is less likely to be estopped from asserting these claims against Ambry.

    Ambry GeneticsMyriad's Relief Requested in its complaint includes
    judgment of patent infringement, an injunction, an accounting and damages, delivery for destruction of all "products"
    that infringe any of the asserted claims, a finding of willful infringement,
    and a request for attorneys' fees, enhanced damages and costs of suit.  Myriad also demands a jury trial.

    As has been discussed in earlier posts, some of
    these claims (e.g., directed to oligonucleotides)
    may be subject to invalidation on novelty grounds (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  In addition, not
    all assignees are named in the complaint (most notably the U.S. Government "as
    represented by the Secretary of Health") and insofar as any of them are
    adjudged to be indispensible parties, any unwillingness to be joined might cause
    Myriad procedural difficulties.  But it
    is significant that Myriad has decided to assert these patents, and its
    continued ability to do so illustrates one of the generally unappreciated
    aspects of the Myriad case.  Plaintiffs in that case and their supporters,
    the ACLU and Public Patent Foundation, chose the claims against which to
    assert their challenge to the validity of Myriad's patents.  Which means, of course, that they chose not to challenge the claims Myriad is
    now asserting, leaving the plaintiffs (including breast cancer patients)
    without the full and complete remedy they no doubt were promised and that the
    press seems to believe the Supreme Court's June 13 decision gave
    them (see "Reaction to Supreme Court's Decision in AMP v. Myriad" and "Does the Myriad Decision Presage a Golden Age of Patent-Free Personalized Medicine?").  Instead, plaintiffs challenged claims to isolated DNA (characterized as "genes"),
    even though such claims are not infringed by the practice of modern genetic
    diagnostic methods.  The result of these strategic (and ultimately
    political or at least public-relations focused) decisions is that Myriad owns
    or has licensed patents that presumptively preclude Ambry Genetics or any other
    provider from offering BRCA gene-directed genetic diagnostic tests until these
    patents expire in the next few years.  In
    short, the parties are in exactly the same position that existed prior to the
    Myriad suit.  While this outcome should
    have been expected, it raises doubts about the consensus narrative of what "everybody
    knows" this case was all about.

  • BIO IP & Diagnostics Symposium

    Biotechnology Industry Organization (BIO)The Biotechnology
    Industry Organization (BIO) will be holding an IP & Diagnostics Symposium
    from 8:00 am to 2:45 pm on July 22, 2013 at the Hilton Alexandria Old Town
    Hotel in Alexandria, VA.  The Symposium will
    review the current patent law landscape and evaluate the impact on both the
    genetic diagnostics and biopharmaceutical sectors.  The program will
    review IP issues for diagnostics and companion diagnostics, and explore
    potential regulatory dimensions.  In hosting the event, BIO aims to inform
    industry and government alike on how to move the science forward in the current
    climate.  The Symposium will offer the
    following presentations and sessions:

    • Keynote breakfast
    — Jeffrey N. Peterson, Chief Executive Officer, Target Discovery, Inc.

    • Session 1 — Obtaining Patent Protection — Patent Docs author Donald Zuhn of
    McDonnell Boehnen Hulbert & Berghoff LLP will moderate a panel including Mary
    Till, Legal Advisor, Office of Patent Legal Administration, U.S. Patent &
    Trademark Office; Duane Marks, Patent Counsel, Roche Diagnostics Operations,
    Inc.; and Patent Docs author Kevin
    Noonan     of McDonnell Boehnen Hulbert & Berghoff LLP

    • Session 2 —
    Regulatory & Reimbursement — Jennifer L. Fox of Brinks Hofer Gilson &
    Lione will moderate a panel including Sheila D. Walcoff, Founding Principal, Goldbug Strategies LLC

    • Session 3
    (Working Luncheon) — Business Development & Strategic Deals — Eric Steffe
    of Sterne Kessler Goldstein & Fox LLP will moderate a panel including Tim
    Shea of Sterne Kessler Goldstein & Fox LLP; Pia Maria Gargiulo, Managing
    Director, Companion Diagnostics, Precision for Medicine; Mollie Roth of PGx
    Consulting; and Zoran Zdraveski, Senior Director of Intellectual Property,
    Epizyme, Inc.

    An agenda for the
    Symposium, including a list of speakers, moderators, and panelists can be
    obtained here.

    Although there is
    no registration fee for the Symposium, space is limited and attendees must
    register for the program.  A registration
    form can be obtained here.  Additional information regarding the Symposium can be found on BIO's Patently Biotech blog.

  • Coalition of University TTOs File Amicus Brief in Lighting Ballast Control LLC v. Philips Electronics North America Corp.

    By Kevin
    E. Noonan     —

    PUBPATIn
    his novel My Summer in a Garden
    (1870), Charles Dudley Warner famously said "Politics makes
    strange bedfellows."  That aphorism
    is illustrated once again in the joining of the Public Patent Foundation with
    eight technology transfer organizations and the Association of University of
    Technology Managers,* urging the Federal Circuit to overturn its decision in Cybor Corp. v. FAS Technologies, Inc.,
    138 F.3d 1448, 1456 (Fed. Cir. 1998) (en banc), that claim construction by a
    district court is entitled to no deference.

    The
    brief (~7 page) amicus brief addresses the three questions posed by the Federal
    Circuit for en banc review:

    1) Should [the] court
    overrule Cybor []?

    2) Should [the] court afford
    deference to any aspect of a district court's claim construction?

    3) If so, which aspects should be
    afforded deference?

    As
    to the first question, the brief answers in the affirmative, simply stating
    that Cybor should be overruled to the
    extent it places factual determinations "outside the realm of deferential
    review" for reasons set forth in the remainder of the brief.

    AUTMRegarding
    the second question, the brief notes that claim construction is a mixed
    question of law and fact, a situation not unusual in patent law, citing
    obviousness and enablement as being questions of law based on frequently
    disputed facts.  A district court's
    factual determination relating to these questions is reviewed under a "substantial
    evidence" standard (e.g., Martek
    Biosciences Corp. v. Nutrinova, Inc.,     579 F.3d 1363, 1378
    (Fed. Cir. 2009) (enablement); Honeywell Int'l,
    Inc. v. United States    , 609 F.3d 1292, 1297 (Fed. Cir. 2010) (obviousness).  The brief also notes that the Supreme Court's
    decision in Markman v. Westview Instruments does not mandate the approach taken
    by the Federal Circuit in Cybor.  Even certain members of the Court (former
    Chief Judge Michel, current Chief Judge Rader) don't agree with the Court's
    approach in Cybor:

    It seems to me that the claim construction question often
    cannot be answered without assessing, at least implicitly, what the average
    artisan knew and how she thought about the particular technology when the
    patent claims were written.  To make such determinations, the trial judge
    necessarily relies upon prior art documents and other evidence concerning the
    skill of the ordinary artisan at the relevant time.  Indeed, trial judges are
    arguably better equipped than appellate judges to make these factual
    determinations, especially in close cases.  In such instances, perhaps we should
    routinely give at least some deference to the trial court, given its greater
    knowledge of the facts.

    Amgen Inc. v. Hoechst Marion
    Roussel, Inc.    ,
    469 F.3d 1039, 1041 (Fed. Cir. 2006) (Michel, C.J. and Rader, J., dissenting).

    And
    other members of the Court have gone further, citing Fed. R. Civ. Pro. Rule
    52(a); see Phillips v. AWH Corp.,
    415 F.3d 1303, 1332 (Fed. Cir. 2005) (en banc) (Mayer, J., and Newman, J.,
    dissenting).  The TTO's amicus brief states:

    The
    Amici agree with these dissenting opinions — there is no reason to treat the
    appellate review of factual underpinnings related to claim construction any
    differently than any other factual determinations.  The resulting deference will
    ensure a greater predictability for the claim construction proceeding, and will
    avoid having to "re-try" the factual underpinnings of claim
    construction on appeal.

    The
    advantages of adopting this standard of review would include "a greater
    predictability for the claim construction proceeding" and "avoid[ing]
    having to 're-try' the factual underpinnings of claim construction on appeal."  The resulting "[p]redictability and
    avoidance of duplicative effort are of particular importance to
    universities, related institutions, and
    the organizations to which such institutions belong," according to the
    brief, "particularly since patent litigation, with its attendant costs and
    uncertain outcome already places such institutions in a disadvantaged position."

    Finally,
    the brief argues that a district court's factual determinations incident to
    claim construction should be reviewed under a "substantial evidence"
    standard.  The brief illustrates the
    consequences and justifications of their approach using the case at bar:

    In
    resolving this question [i.e., the meaning of a disputed claim term], the
    district court evaluated evidence in the form of expert deposition testimony
    (and the parties' arguments thereon) regarding how persons skilled in the art
    would understand the limitation[].  After
    such evaluation, the district court found that such limitation indeed "corresponds
    to a class of structures."

    The
    district court's finding regarding the meaning of [the disputed claim term] to
    those of ordinary skill in the art was indisputably one of fact.  The subject
    patent itself contained no evidence of how such hypothetical persons would
    understand that term, and the parties were consequently required to rely upon
    extrinsic evidence in the form of expert depositions in order to support their
    respective positions on the subject.  As with any other factual finding
    regarding claim construction, this factual finding is entitled to deference in
    the appellate review thereof.

    One relevant argument in favor of
    discarding the claim construction analysis from Cybor is that in so doing the Federal Circuit might avoid the high
    percentage of reversals of district court claim construction (~30-40%
    according to some legal academics).  The
    counter-argument is that often, and perhaps the majority of the time, a
    district court's factual determinations can be dispositive of the claim
    construction exercise.  In these
    circumstances, giving even a "substantial evidence" level of
    deferential review to these factual determinations may vitiate any de novo review by the Federal Circuit of
    how the claims are properly construed as a matter of law.

    The Federal Circuit is scheduled
    to hear the appeal en banc on September 13, 2013.

    *
    The amici are: Association of University Technology Managers (AUTM), NUtech
    Ventures, Inc. (University of Nebraska – Lincoln), UNeMED Corporation
    (University of Nebraska Medical Center), STC.UNM (University of New Mexico),
    Wisconsin Alumni Research Foundation (University of Wisconsin), Colorado State
    University Research Foundation, Public Patent Foundation, Tec Edmonton
    (University of Alberta and City of Edmonton), The University of Pittsburgh of
    The Commonwealth System of Higher of Education, and Newsouth Innovations
    (University of New South Wales, Australia)

    Hat tip to Gray on Claims for providing the amicus brief.

  • USPTO Files Reply Brief in Exelixis v. Rea

    By Donald Zuhn —

    USPTO SealAt the end of June, the
    U.S. Patent and Trademark Office filed its reply brief with the Federal Circuit
    in Exelixis, Inc. v. Rea.  The appeal involves two decisions by the
    Eastern District of Virginia involving the impact of a Request for Continued
    Examination (RCE) on the calculation of patent term adjustment (PTA) for a patent, and in
    particular, on the amount of B-Delay an applicant can obtain after filing an RCE.  A discussion of the first decision to come
    out of the Eastern District of Virginia (Exelixis
    I    ), which was issued by Judge T. S. Ellis III on October 1, 2012, and which
    the USPTO has appealed, can be found here.  The opinion for the second decision (Exelixis II) — which was issued by
    Judge Leonie M. Brinkema on January 28, 2013, and which Exelixis has appealed,
    can be found here.

    The USPTO brief begins by
    noting that the Office's issue on appeal is:

    [W]hether this Court should uphold the
    agency's longstanding interpretation of [35 U.S.C. § 154(b)(1)(B)(i)], under
    which any time consumed by an applicant's request for continued examination
    ("RCE") is excluded from the calculation of patent term adjustment
    under subsection 154(b)(1)(B) regardless of when the applicant filed the RCE.

    ExelixisWhile Exelixis argues that
    an RCE filed after the 3-year deadline (i.e.,
    three years after the application was filed) should not impact the amount of
    B-Delay a patent can accrue, the USPTO argues that regardless of whether an RCE
    is filed before or after the 3-year deadline, a patent should not accrue
    B-Delay after the RCE is filed.  The
    Office summarizes Exelixis' issue on appeal as being:

    [W]hether the Court should defer to the
    USPTO's definition of "any time consumed by continued examination of the application
    requested by the applicant under section 132(b)" to include all time elapsed
    between filing of an RCE and issuance of a patent.

    In arguing that the
    Office's interpretation of the statute "avoids absurd results, realizes
    Congress's intent, and best makes sense of the provision as a whole," the
    USPTO brief notes that the District Court in Exelixis II "explained[ that]
    an RCE adds time to the processing of the application but delay after the
    filing of an RCE 'emanates solely from an applicant's original failure to file
    an application fit for a notice of allowance.'"  Therefore, the USPTO contends that the filing
    of an RCE is applicant-caused delay and not PTO-caused delay.  The brief argues that
    "although the statute is ambiguous, the USPTO's interpretation is by far
    the better reading of the statute and this Court should defer to it under Skidmore."

    With respect to the
    ambiguity of the statute, the brief states that "the text of 35 U.S.C. § 154(b)(1)(B)
    is ambiguous," in that "[i]t can be read as providing that time
    associated with the filing of an RCE is excluded from the B-delay category of
    PTA, regardless of when the RCE is filed, or it can be read to apply only to
    RCEs filed within the first three years." 
    The brief asserts that "[r]eading the statute as a whole, the
    USPTO's interpretation is by far the better way to resolve this textual
    ambiguity."  Fearing that Exelixis'
    interpretation of the statute would permit submarine patents, the brief explains
    that "an applicant could file an overly broad patent application,
    repeatedly fail to address the examiner's reasons for rejection, and then
    narrow it only in a later RCE."

    As for Exelixis' issue on
    appeal, the brief contends that:

    The USPTO has discretion under Section 132(b)
    to define the RCE process and to determine when it is completed.  The USPTO has done so and determined that the
    RCE process continues until the patent is actually issued because, once an RCE
    is requested, "any further processing or examination of the application,
    including granting of a patent, is by virtue of the continued
    examination."

    The brief notes that
    "Congress left it to the USPTO to define the process for 'continued
    examination' under Section 132(b), including when that process begins and
    ends."  And as the brief explains, the Office defined the
    process to be such that "[o]nce an RCE is requested, 'any further
    processing or examination of the application, including granting of a patent,
    is by virtue of the continued examination,'" meaning that "any time
    following the filing of an RCE is consumed by the RCE."

    In response to Exelixis' argument that examination
    cannot include the period between the issuance of the notice of allowance and
    the issuance of the patent because the notice of allowance states that the
    application "has been examined" and no actual examination occurred
    after that time, the brief counters that:

    In the patent context . . . the word
    "examination" is not limited in such a way.  The period of examination spans the entire
    time that the application is pending before the USPTO.  See
    35 U.S.C. § 131 (indicating that issuance immediately follows
    examination).  This understanding of the
    term "examination" is consistent with the USPTO's regulation
    governing "adjustment of patent term due to examination delay," which
    includes patent term adjustment for delays in issuing the patent after payment
    of the issue fee.  See 37 C.F.R. § 1.703(a)(6) (emphasis added).  Likewise, late payment of the issue fee and
    requests to defer issuance of a patent after payment of the issue fee, both of
    which must occur after the notice of allowance is issued, represent a failure
    of the applicant to engage in reasonable efforts to conclude "processing
    or examination" of the application.

    As for Exelixis' argument
    that it is unfair to deny an applicant PTA for time between the notice of
    allowance and the issue date because the USPTO controls the time it takes to
    issue a patent, the brief indicates that:

    As an initial matter, this
    is only partially true.  The USPTO only
    controls the time after payment of the issue fee and satisfaction of any other
    outstanding requirements by the applicant. 
    The applicant controls the time it takes to pay the issue fee and
    fulfill any other necessary requirements. 
    In Exelixis II, it took Exelixis
    almost three months (from July 1 to September 30) to pay the issue fee, accounting
    for the majority of the time that elapsed between the notice of allowance and
    the patent issue date.  Even though
    Exelixis, not the USPTO, was responsible for that time, and Exelixis waited
    until the last day to pay the issue fee, Exelixis now requests PTA for the
    entire period and asserts that it is "time consumed by [the USPTO's]
    administrative delay."

    (citation omitted).

    The brief also notes that
    "PTA is . . . available where there are undue USPTO delays in issuing the
    patent [e.g., when the USPTO takes more
    than four months to issue a patent after the issue fee is paid]."  Explaining that "PTA
    is designed to compensate for delays by the USPTO," the brief argues that
    "[i]t is not punitive to decline to grant PTA for delays that are not due
    to a failure on the part of the USPTO," and therefore concludes that
    "[g]iving PTA for '[t]his applicant-caused delay is incompatible with the
    concept of B-delay PTA, which is fundamentally anchored to PTO-caused
    delay.'"

  • Webinar on AIA and Patent Prosecution

    Strafford #1Strafford
    will be offering a webinar/teleconference entitled "AIA and Patent Prosecution: Navigating the
    Ethical Grey Areas" on July 24, 2013 from 1:00 to 2:30 pm
    (EDT).  Mercedes K. Meyer of Drinker
    Biddle & Reath, and Patent Docs
    author Dr. Kevin E. Noonan of McDonnell Boehnen Hulbert & Berghoff will
    provide guidance on the legal ethics implications of the new patent system and
    recent changes in patent law, and offer best practices for staying on the right
    side of the ethical line in patent prosecution. 
    The webinar will review the following questions:

    •
    How has the AIA changed the ethical landscape for patent attorneys?
    •
    What are the legal ethics implications of supplemental examination?
    •
    What steps should patent counsel take to ensure compliance with legal ethics
    requirements?

    The
    registration fee for the webinar is $297 ($362 for registration and CLE
    processing).  Those interested in
    registering for the webinar, can do so here.

  • Webinar on Patent Trolls

    MBHB Logo 2McDonnell
    Boehnen Hulbert & Berghoff LLP will be offering a live webinar entitled
    "Are We Innovators, or Are We
    Trolls: The Slippery Slope of Defining A Patent Troll" on July 30,
    2013 from 10:00 am to 11:15 am (CT). 
    MBHB attorneys Alison J. Baldwin and Sarah J. Duda will cover proposed
    governmental anti-patent troll actions and initiatives from both the White
    House and Congress.  Topics to be covered
    include:

    • An overview of proposed changes including
    legislative and executive proposals
    • How the proposed changes impact whether different
    business organizations are considered patent trolls
    • Whether your organization may be a patent troll
    under the proposed changes
    • Effects on organizations falling under the
    proposed changes

    While
    there is no fee to participate, attendees must register in advance.  Those wishing to register can do so here.  CLE credit is pending for the states of
    California, Georgia, Illinois, North Carolina, New Jersey, New York and
    Virginia.

  • CLE on FTC v. Actavis

    LSI - Law Seminars International - blueLaw
    Seminars International (LSI) will be offering a one-hour telebriefing entitled
    "FTC v. Actavis: Practical Implications of the Landmark
    Supreme Court Decision" on July 16, 2013 from 3:00 to 4:00
    pm (Eastern).  Jarod M. Bona of DLA Piper
    will moderate a panel that includes Markus H. Meier, Assistant Director, Health
    Care Division, Bureau of Competition, Federal Trade Commission; and Rohit K.
    Singla of Munger Tolles & Olson LLP. 
    The panel will discuss the practical implications of this landmark case
    and related antitrust issues involving pharmaceutical patents.  Among the topics to be covered are:

    •
    Practical tips for drafting patent-settlement agreements going forward
    •
    FTC perspective on reverse-payment settlements and the underlying litigation of
    the decision
    •
    Possible implications beyond pharmaceutical-patent settlements
    •
    Likely impacts on future litigation and patent settlements

    A
    Q&A will follow the presentation and last for up to 30 minutes.

    The
    registration fee is $150 per caller and $100 for each additional person on the
    same line who desires continuing education credit.  Those interested in registering for the
    telebriefing, can do so here.

  • ABA 2013 Annual Meeting

    BrochureThe American Bar
    Association (ABA) will be holding its 2013 Annual Meeting from August 8-11,
    2013 in San Francisco, CA.  During the
    Annual Meeting, various ABA sections and divisions will be offering more than
    250 CLE programs, including the following programs that will be offered by the
    Intellectual Property Law section:

    • European Patent
    Litigation: A Brand New Era
    • Conjoint
    Analysis: Its Role in Determining Patent Damages and its Application to the
    Entire Market Value Rule
    • Navigating the
    Patent Thicket
    • Was Prometheus a Flook? The Outlook for Patent Eligibility of Software, Biotech, and
    Related Technologies
    • Patent Markets
    Evolution — The Buying, Selling and Brokering of Patent Assets

    A schedule of programs and events being offered by the Section of
    Intellectual Property Law at the ABA Annual Meeting can be found here.  Information regarding registration fees can
    be found here.  Those interested in registering for the
    Annual Meeting can do so here.

  • Organic Seed Growers & Trade Ass’n v. Monsanto Co. (Fed. Cir. 2013)

    By Kevin E. Noonan —

    OSGATASomewhat
    lost in the hubbub over the Supreme Court's ruling in AMP v. Myriad was the Federal Circuit's decision, just a few days
    earlier, in Organic Seed Growers & Trade Ass'n v. Monsanto Co.  That case is the latest windmill tilt by
    Cardozo Law School's Public Patent Foundation (PubPat) over biotechnology
    patents, which it brought on behalf of "a
    coalition of [several dozen] farmers, seed sellers, and agricultural
    organizations."

    MonsantoThe
    case involved a declaratory judgment action against 23 Monsanto patents* brought
    by plaintiffs who alleged that they were at risk of patent infringement
    liability due to "inadvertent" infringement of Monsanto's patents
    relating to recombinant seeds, specifically the company's Roundup Ready® seeds used with the glyphosate
    herbicide, Roundup®.  Plaintiffs alleged as
    their injury that they were at risk for inadvertent infringement, that they
    were forced to forego planting even conventional "corn,
    cotton, canola, sugar beets, soybeans, and alfalfa" due to the extent to
    which these crops were transgenic ("over 85-90% of all soybeans, corn,
    cotton, sugar beets, and canola grown in the U.S. contains Monsanto's patented
    genes") and that they were burdened by the cost and efforts they expended to avoid
    infringing.  Plaintiffs also noted that Monsanto
    has brought 144 infringement suits between 1997 and 2010, and settled ~700 more
    over that time.  Showing that PubPat had
    learned the lessons of the Myriad case
    regarding standing, "[a]t least one plaintiff
    [Bryce Stephens] declared that the fear of suit by Monsanto is the sole reason
    he refrained from cultivating organic corn and soybeans, and that he would
    resume growing those crops if that threat were eliminated."

    Shortly
    after they initiated the lawsuit, plaintiffs asked Monsanto for an express
    covenant not to sue.  While demurring
    from supplying such a covenant, Monsanto referred plaintiffs to its website,
    wherein there was an explicit statement regarding "inadvertent"
    contamination and infringement:

    It has never been, nor will
    it be Monsanto policy to exercise its patent rights where trace amounts of our
    patented seeds or traits are present in farmer's fields as a result of
    inadvertent means.

    Moreover,
    Monsanto's attorneys by letter further expanded on the company's absence of any
    intent to sue plaintiffs:

    Monsanto is unaware of any circumstances that would give rise to any claim for
    patent infringement or any lawsuit against your clients.  Monsanto therefore
    does not assert and has no intention of asserting patent-infringement claims against
    your clients.  You represent that "none of your clients intend to possess,
    use or sell any transgenic seed, including any transgenic seed potentially
    covered by Monsanto's patents."  Taking your representation as true, any
    fear of suit or other action is unreasonable, and any decision not to grow
    certain crops unjustified.

    In
    view of these representations, the District Court found that plaintiffs did not
    have standing to sue under the Declaratory Judgment Act and dismissed the
    lawsuit.

    Federal Circuit SealThe
    Federal Circuit affirmed, in an opinion by Judge Dyk joined by Judges Bryson
    and Moore.  The opinion set forth the "ground rules" of standing from
    the Supreme Court's decision in MedImmune, Inc. v. Genentech, Inc., 549
    U.S. 118, 127 (2007):

    "Basically, the question in each case is whether the facts alleged,
    under all the circumstances, show that there is a substantial controversy,
    between parties having adverse legal interests, of sufficient immediacy and
    reality to warrant the issuance of a declaratory judgment," citing Md.
    Cas. Co. v. Pac. Coal & Oil Co.    , 312 U.S. 270, 273 (1941).

    The
    Federal Circuit had applied these rubrics in implementing this precedent:

    Although there is no bright-line rule applicable to patent cases, we have held
    that "Article III jurisdiction may be met where the patentee takes a
    position that puts the declaratory judgment plaintiff in the position of either
    pursuing arguably illegal behavior or abandoning that which he claims a right
    to do," citing SanDisk Corp. v. STMicroelectronics, Inc., 480 F.3d
    1372, 1380–81 (Fed. Cir. 2007)

    Here,
    "the question in this case is not whether the appellants' subjective fear
    of suit by Monsanto is genuine, but whether they have demonstrated a "'substantial
    risk' that the harm will occur, which may prompt [them] to reasonably incur
    costs to mitigate or avoid that harm," citing Monsanto Co. v. Geertson
    Seed Farms    , 561 U.S. ___, ___, 130 S.Ct. 2743, 2754–55 (2010).  The plaintiffs' asserted basis for their
    belief that they were at risk for infringement liability was "Monsanto's
    evident history of aggressive assertion of its transgenic seed patents against
    other growers and sellers"; however, simply a patentee's activities
    against other defendants are not always enough to confer jurisdiction,
    according to the panel opinion, relying on Arkema Inc. v. Honeywell Int'l,
    Inc.    , 706 F.3d 1351, 1356 (Fed. Cir. 2013), Micron Tech, Inc. v. MOSAID
    Techs., Inc.    , 518 F.3d 897, 901 (Fed. Cir. 2008), Prasco, LLC v. Medicis
    Pharm. Corp.    , 537 F.3d 1329, 1341 (Fed. Cir. 2008), and Holder v.
    Humanitarian Law Project    , 561 U.S. ___, 130 S.Ct 2705, 2717 (2010), and
    requires the court to look at the totality of the circumstances in each
    case.  Which, on these facts, required
    the court to assess whether Monsanto's "representations" regarding
    inadvertent infringers was sufficient to negate the company's "evident
    history of aggressive assertion" of it patents.

    Monsanto
    (at oral argument) defined "inadvertent" infringers to be those whose
    crops become accidentally contaminated and who don't spray their fields with
    Roundup (consistent with their position in Bowman).  The District Court, the parties, and the panel
    accepted as inevitable that the plaintiffs' crops would be contaminated with
    Monsanto's recombinant seed, based on the predominance (~50% on average, with
    some crops comprising 90%) of such seeds in the seed stock of many conventional
    crops, stemming from "windblown pollen or seeds from genetically modified
    crops or other sources" (a high standard in view of their counsel's
    assertion, at oral argument in the Bowman
    case, that it would take winds such as those in Hurricane Sandy to blow a
    transgenic soybean seed onto a farmer's field).

    The
    opinion also notes that "[t]here is [] a substantial risk that at least
    some of the appellants could be liable for infringement if they harvested and
    replanted or sold contaminated seed" despite the opinion also stating that
    "the [Supreme] Court's recent decision in Bowman v. Monsanto Co. leaves
    open the possibility that merely permitting transgenic seeds inadvertently
    introduced into one's land to grow would not be an infringing use."  The Federal Circuit's own precedent is to the
    contrary, such that "one who, within the meaning of the Patent Act, uses
    (replants) or sells even very small quantities of patented transgenic seeds
    without authorization may infringe any patents covering those seeds,"
    according to the opinion, citing SmithKline Beecham Corp. v. Apotex Corp.,
    403 F.3d 1331, 1336, 1339–40 (Fed. Cir. 2005); Abbott Labs. v. Sandoz, Inc.,
    566 F.3d 1282, 1299 (Fed. Cir. 2009); and Embrex, Inc. v. Serv. Eng'g Corp.,
    216 F.3d 1343, 1352–53 (Fed. Cir. 2000), regarding the non-existence of "de minimis infringement" (none of
    these cases involved seeds or other "self-replicating"
    technologies).  Accordingly, the Court
    assumed inadvertent infringement would likely occur.

    But
    these technical considerations were not the issue; it was standing, not the
    merits, that was before the Court.  The
    question was whether Monsanto's "representations" that it will not sue
    for inadvertent infringement were sufficient to "moot any potential
    controversy" and thus defeat standing.  The Court looked for guidance from the Supreme Court's recent Already,
    LLC v. Nike, Inc.     case, where an express covenant not to sue from a trademark
    owner defeated declaratory judgment jurisdiction.  568 U.S. ___, ___, 133 S.Ct.
    721, 732 (2013).  Thus the Federal Circuit was
    faced with determining whether an express covenant was required or if Monsanto's
    reassurances would do.

    The Court found that they would.  "Taken
    together, Monsanto's representations unequivocally disclaim any intent to sue
    appellant growers, seed sellers, or organizations for inadvertently using or
    selling 'trace amounts' of genetically modified seeds," the panel found,
    wherein the panel interpreted "trace amounts" to be approximately one
    percent.  "We conclude that Monsanto
    has disclaimed any intent to sue inadvertent users or sellers of seeds that are
    inadvertently contaminated with up to one percent of seeds carrying Monsanto's patented
    traits," said the Court.

    Important
    to the panel decision was the effect of judicial estoppel on Monsanto and its
    representations to the Court that it had "no intention of asserting
    patent-infringement claims" against plaintiffs or other "inadvertent"
    infringers.  The opinion set forth the "main
    factors" that raise the estoppel:

    (1) a party's later position is "clearly inconsistent" with its prior
    position, (2) the party successfully persuaded a court to accept its prior
    position, and (3) the party "would derive an unfair advantage or impose an
    unfair detriment on the opposing party if not estopped," citing New
    Hampshire v. Maine    , 532 U.S. 742, 750–51 (2001).

    Any
    future lawsuit brought by Monsanto against these plaintiffs would satisfy "all
    three [of these] factors," according to the Court.  Somewhat wryly, the opinion notes that this
    conclusion was "wisely acknowledged" by Monsanto's counsel at oral
    argument.

    One
    drawback to the Court's certainty regarding this conclusion is the limitation in
    Monsanto's representations that only individuals producing crops having only "trace
    amounts" produced from infringing recombinant seed would fall within the
    scope of those representations, including the company's reluctance to include
    within their commitment not to sue crops having greater than such trace amounts
    but that were not produced using Roundup® treatment.  While the panel noted that "we cannot
    conclude that Monsanto has disclaimed any intent to sue a conventional grower
    who never buys modified seed, but accumulates greater than trace amounts of
    modified seed by using or selling contaminated seed from his fields," none
    of the plaintiffs was willing to allege that they did, would or planned to "fall
    outside Monsanto's representations" to the Court in this regard.  All plaintiffs alleged that they were "using
    their best efforts" not to
    produce crops comprising more than "trace amounts" of recombinant
    seed, and thus they did not allege activities that would put them at patent
    infringement risk — a requirement for the plaintiffs to have standing under
    Supreme Court (Already) as well as
    Federal Circuit precedent (e.g., Benitec Austl., Ltd. v. Nucleonics, Inc.,
    495 F.3d 1340, 1346–50 (Fed. Cir. 2007)).

    Finally,
    the Court found that allegations of a "chilling effect" or other
    subjective apprehensions of patent infringement liability risk were not
    sufficient to confer standing, because they did not amount to "a claim of
    specific present objective harm or a threat of specific future harm,"
    citing Laird v. Tatum, 408 U.S. 1, 13–14 (1972) or a "substantial
    risk" of liability:

    The appellants have not made that showing here, because the future harm they
    allege — that they will grow greater than trace amounts of modified seed, and
    therefore be sued for infringement by Monsanto — is too speculative to justify
    their present actions.  Parties "cannot manufacture standing merely by
    inflicting harm on themselves based on their fears of hypothetical future harm,"
    citing Clapper v. Amnesty Int'l USA, 568 U.S. ___, _____, 133 S.Ct. 1138,
    1151 (2013)

    Because
    the Court found that Monsanto had made binding representations that removed any
    risk of suit against plaintiffs who produced crops comprising trace amounts of
    Monsanto's recombinant seed, and that plaintiffs had made no allegations that
    they had any "concrete plans or activities" to make, use or sell
    greater than trace amounts of Monsanto's seed, these plaintiffs had failed to
    show any risk of suit and thus "lacked an essential element of standing"
    required by the Declaratory Judgment Act.

    At
    least until the Supreme Court decides to grant certiorari.

    Organic
    Seed Growers & Trade Ass'n v. Monsanto Co    . (Fed. Cir.
    2013)
    Panel:
    Circuit Judges Dyk, Bryson, and Moore
    Opinion by Circuit Judge Dyk

    *
    U.S. Patent Nos. 5,322,938 ("DNA sequence for enhancing the efficiency of
    transcription"); 5,352,605 ("Chimeric genes for transforming plant
    cells using viral promoters"); 5,362,865 ("Enhanced expression in
    plants using non-translated leader sequences"); 5,378,619 ("Promoter
    for transgenic plants"); 5,424,412 ("Enhanced expression in plants");
    5,463,175 ("Glyphosate tolerant plants"); 5,530,196 ("Chimeric
    genes for transforming plant cells using viral promoters"); 5,554,798 ("Fertile
    glyphosate-resistant transgenic corn plants"); 5,593,874 ("Enhanced
    expression in plants"); 5,641,876 ("Rice actin gene and promoter");
    5,659,122 ("Enhanced expression in plants using non-translated leader
    sequences"); 5,717,084 ("Chimaeric gene coding for a transit peptide
    and a heterologous peptide"); 5,728,925 ("Chimaeric gene coding for a
    transit peptide and a heterologous polypeptide"); 5,750,871 ("Transformation
    and foreign gene expression in Brassica species"); 5,859,347 ("Enhanced
    expression in plants"); 6,025,545 ("Methods and compositions for the
    production of stably transformed, fertile monocot plants and cells thereof");
    6,040,497 ("Glyphosate resistant maize lines"); 6,051,753 ("Figwort
    mosaic virus promoter and uses"); 6,083,878 ("Use of N-
    (phosphonomethyl) glycine and derivatives thereof"); 6,753,463 ("Transformed
    cotton plants"); 6,825,400 ("Corn plants comprising event
    PV-ZMGT32(nk603)"); RE38,825 ("Glyphosate tolerant plants"); and
    RE39,247 ("Glyphosate-tolerant 5-enolpyruvylshikimate-3-phosphate synthases").

  • After Myriad: A Herd of Elephants in the Room

    Guest
    Post by Sean Brennan —

    MyriadAs
    we all know by now, the Supreme Court last month decided that isolated genes
    are not eligible for patenting.  Although
    seemingly drawing a clear-cut distinction between DNA molecules having the same
    sequence as that which occurs in nature (genes), and DNA molecules having
    different sequences from those that occur in nature (cDNA) (see
    Patent Docs     posts here
    and here), the decision leaves
    a host of unsettled questions about the patent-eligibility of numerous biologicals.  Although ostensibly concerned with human
    genes, the reasoning supporting the decision could be used to call into
    question the patent-eligibility of compositions ranging from purified metabolites
    (such as antibiotics) to isolated proteins to procaryotic genes.

    Non-human
    genes

    Although
    the question addressed by the Court was "Are human genes patentable?",
    in its decision the Court couldn't seem to decide whether its decision applied strictly
    to human genes or to genes in general.  In framing the question, the Court stated that the case "requires
    us to resolve whether a naturally occurring segment of . . . DNA is patent eligible . . . by virtue of its isolation from the rest of the human genome."  (Slip.
    Op. at 1, emphasis added).  But in
    announcing its decision, the Court appeared to have lost sight of the "human"
    limitation when it stated:  "we hold that a naturally occurring DNA segment
    is a product of nature and not patent eligible merely because it has been
    isolated" (Id.); "separating
    [a] gene from its surrounding genetic material is not an act of invention"
    (Id. at 12); and "[w]e merely
    hold that genes and the information they encode are not patent eligible under §
    101 simply because they have been isolated from the surrounding genetic
    material" (Id. at 18).

    Supreme Court Building #2Thus,
    the decision leaves open the question of whether it is only human genes that
    are not patent-eligible (i.e., did
    the Supreme Court buy the "you can't patent my body" argument?) or is
    any gene, from any organism, barred from patent eligibility?  It is difficult to understand how the Court
    could justify one standard for human genes and another for genes of other
    species.

    This
    being the case, the decision would seem to doom the patent-eligibility of
    procaryotic genes; the vast majority of which do not contain introns.  Although it is possible to reverse-transcribe
    a procaryotic mRNA molecule to generate a cDNA from a procaryotic gene, such a
    nucleic acid molecule would not have a sequence different from the sequence of
    the gene as it occurs in nature.

    This
    result would be unfortunate, since new bacterial species are being discovered
    every day, and many of these contain genes encoding proteins that are useful
    for processes such as pesticide production and bioremediation.  It would also set up a technology-specific
    distinction between biotechnological and pharmaceutical practice, in which it is
    typical to obtain composition claims for the first disclosure of a new
    compound.

    Vectors

    If
    it is no longer possible to claim an isolated gene per se, might we still be able to claim a gene sequence as a
    component of a vector?  Unfortunately,
    the decision provided no guidance on this point, because none of Myriad's
    claims reciting BRCA genes as components of a vector or expression system (e.g., claims 8-11 of U.S. Patent No. 5,747,282)
    were at issue.  Although it is undisputed
    that the combination of a gene with one or more of a heterologous promoter,
    termination site, regulatory sequence(s), replication origin, or antibiotic
    resistance marker is a composition that does not occur in nature; I worry that,
    given the current judicial climate (see Mayo
    v. Prometheus    ), addition of heterologous sequences to a newly isolated gene
    will be dismissed as "insignificant post-solution activity."  After all, cloning vectors and expression vectors
    are standard materials that can be purchased from any one of a dozen or more
    suppliers.  Then again, it could turn out
    that certain vectors (and/or heterologous sequences) will be considered
    standard and others not, so that the patent eligibility of a gene might end up
    depending upon what other sequences are attached to it.  A good deal of biotech practice over the next
    few years may well involve figuring out how much we need to "dress up"
    a gene before it can be "taken out" into the realm of patent-eligibility.

    Informational content

    The
    Court seemed to imply that identity of informational content
    between a cloned gene and a naturally-occurring gene is what renders gene
    sequences patent-ineligible; and not the (supposed) identity of chemical
    structure between the two:  "Myriad's
    claims are simply not expressed in terms of chemical composition, nor do they
    rely in any way on the chemical changes that result from the isolation of a
    particular section of DNA.  Instead, the
    claims understandably focus on the genetic information encoded in the BRCA1 and
    BRCA2 genes." (Slip Op. at 14-15).  "Myriad . . . is concerned primarily with the information contained in the
    genetic sequence, not with the
    specific chemical composition of a particular molecule."  (Id. at 15, emphasis in original).

    If
    this is the case, I wonder why even cDNA was found to be patent-eligible.  Inasmuch as the informational content of most
    DNA molecules resides in their ability to encode a polypeptide sequence, a cDNA
    is no different in this respect from the intron-containing gene sequence from
    which it is derived.

    At
    the risk of presenting a somewhat far-fetched example to make another point, I note
    that it is possible to create recombinant gene sequences that do not have the
    same chemical structure, but nonetheless contain the same informational
    content, as a naturally-occurring gene. 
    For instance, certain bacteriophages contain hydroxymethyluracil (HMU)
    instead of thymine in their DNA.  Imagine
    an enterprising geneticist who develops a cloning system, based on this
    bacteriophage, that generates cloned DNA containing HMU instead of
    thymidine.  The cloned gene now has a
    structure that does not occur in the natural gene — is it patent eligible?  It would seem to depend on whether the criterion
    is a different chemical structure or a different information content.  Unfortunately the decision, while leaning
    toward informational content, failed to provide a clear criterion.

    Another
    biological fact that seemed to get lost in the Myriad case is that naturally
    occurring DNA sequences contain epigenetic informational content (the most
    well-known example being methylation of cytosine residues) that is generally
    not present in an isolated cloned gene.  Consequently,
    there are both structural (e.g., methyl
    groups) and informational (gene methylation generally signals transcriptional repression)
    differences between certain isolated genes and their naturally-occurring
    counterparts.  This being so, whatever
    the Court's criterion for eligibility (structural difference or informational
    difference), it would appear that at least some isolated DNA molecules remain
    patent-eligible.

    What is a mutant?

    The
    Court punted on the question of whether mutated sequences are patent-eligible
    and, to make matters worse, provided scant guidance as to what types of sequences
    they considered mutant and, thereby, at least potentially patent-eligible.  The decision failed to comment specifically
    on claims that recited naturally-occurring mutant BRCA sequences (claim 7 of
    the '282 patent and claim 1 of U.S. Patent No. 5,693,473).  But following the Court's "product of
    nature" reasoning would lead to the conclusion that naturally-occurring
    alleles of a gene (some of which might be "mutants" in the classical
    sense of encoding a gene product with altered function) would not be
    patent-eligible.

    On
    the other hand, isolated genes whose sequences have been altered in the
    laboratory would appear to escape at least the "product of nature"
    barrier to eligibility.  The question
    then arises as to whether a gene with a change in a single nucleotide (that
    does not alter the amino acid sequence of the encoded polypeptide) would be
    considered a "mutant."  What
    about a single nucleotide change that did result in an amino acid change?  Would it make any difference if the new amino
    acid encoded by the mutant sequence was a conservative or a non-conservative
    substitution?  Eventually, we may need to
    know how large or significant a change in sequence is necessary to confer "mutant"
    status on an isolated nucleic acid.

    A
    further complication is that assessing whether a laboratory-altered sequence is
    different from a naturally-occurring sequence can present the patent applicant
    with a moving target.  Consider the
    hypothetical heartbreaker in which an applicant constructs a mutant sequence in vitro that is found to be both
    patent-eligible and patentable.  Years
    after the patent is granted, the same sequence is discovered in nature.  Does the patentee's claimed mutant sequence
    become retroactively ineligible?

    Transformed cells

    What
    about a claim to a gene sequence that has been introduced into a heterologous
    cell?  Surely, this is a composition that
    does not occur in nature.  Although such
    claims (e.g., claims 12 and 13 of the '282 patent) were not at issue in Myriad,
    it was just such a composition that was validated as patent eligible by the
    Supreme Court in Chakrabarty (albeit
    the cell in that case comprised more than one heterologous nucleic acid), which
    was cited favorably by the Myriad
    Court.  It's possible that, in the end,
    this may be as close as we'll be able to get to a composition claim to a
    newly-isolated gene.  In many cases, this
    may be good enough, since the principal use for most cloned genes is to express
    their gene product and, in order to do so, the gene is often placed into a
    heterologous cell for expression.

    Proteins

    The
    Court's proscription of naturally-occurring substances would also seem to rule
    out patent eligibility for isolated polypeptides.  In most cases, the amino acid sequence of a
    purified protein is exactly the same as the amino acid sequence of the
    naturally-occurring protein.  One
    normally doesn't even have to break any chemical bonds to purify a protein
    (thus failing the test for eligibility set forth by Judge Lourie in the
    decision below).  In the same way that "Myriad
    did not create or alter any of the genetic information encoded in the BRCA1 and
    BRCA2 genes" and "[t]he location and order of the nucleotides existed
    in nature before Myriad found them"; the amino acid sequence of a
    protein exists in nature before that protein is purified, and it is generally
    not altered by the purification procedure.

    Does
    this mean that isolated proteins are also no longer patent-eligible?  Maybe not, since, in some cases, there are
    structural differences between isolated and naturally-occurring proteins
    (assuming structural distinction is sufficient for eligibility — see above).  For example, if an isolated protein is
    obtained through expression of a recombinant nucleic acid, it often lacks certain
    naturally-occurring post-translational modifications, such as glycosylation or
    phosphorylation.  This is particularly
    true of a eukaryotic protein expressed in a procaryotic host cell.  Thus, it may be possible to obtain a claim to
    a polypeptide that lacks certain post-translational modifications, or contains
    additional modifications not present on the naturally-occurring protein.  Whether such a claim will have any value will
    depend, of course, on whether the isolated protein, containing more or fewer
    post-translational modifications than its naturally occurring counterpart,
    functions effectively for its intended purpose.

    Antibiotics and other naturally-occurring
    compounds

    Denial
    of patent-eligibility to an isolated biological molecule, based on identity to
    its naturally-occurring counterpart, will have repercussions well beyond the
    field of molecular biology.  As other
    commentators have already pointed out, the Myriad
    decision could sound the death knell for patent eligibility of all purified
    naturally-occurring substances (such as antibiotics, certain chemotherapeutics,
    and bacterial metabolites).  In a
    worst-case scenario, even chocolate chip cookies and baseball bats could become
    patent-ineligible.

    Conclusion

    The
    Myriad decision leaves me with a lot
    to be pessimistic about.  But on the
    bright side, keeping my expectations low will at least minimize the chance that
    I'll be disappointed.  I give the Court
    credit for trying to limit the breadth of its decision.  Presumably, they wanted to come-up with a
    clear-cut answer to a clear-cut question and thought they had done so by
    accepting the Solicitor's and Judge Bryson's distinction between genomic DNA
    and cDNA.  But in so doing, the Court let
    not just one, but a whole herd of elephants into the room.  I have a feeling we'll be shoveling for quite
    a while.

    Dr.
    Brennan is a Patent Agent with Brennan IP Services.  He received a Ph.D. in Molecular Biology from
    the University of California, San Diego in 1982, and prior to becoming a patent
    practitioner, Dr. Brennan was a faculty member at the University of Connecticut
    School of Medicine and the University of Southern California.