By Christopher P. Singer —

Last month, the U.S. Patent and Trademark Office announced
that it had updated the training materials to be used by examiners in
the examination of patent applications for compliance with the written
description requirement of 35 U.S.C. § 112, first paragraph.  The revised training materials supersede and replace the previous set of training materials
issued by the Patent Office in 1999.  The new training materials
provide seventeen examples, of which fourteen are specifically related
to biotech inventions.  In particular, the biotech-specific examples
address expressed sequence tags (ESTs) (example 4), a partial protein
structure (example 5), DNA hybridization (example 6), allelic variants
(example 7), bioinformatics (example 8), protein variants (example 9),
a product claimed by its function (example 10), a polynucleotide or
polypeptide sequence sharing percent identity with another sequence
(example 11), antisense oligonucleotides (example 12), antibodies to a
single protein (example 13), antibodies to a genus of proteins (example
14), a genus with widely varying species (example 15), a process claim
where novelty resides in the process steps (example 16), and methods of
using compounds claimed by functional limitations, methods of
identifying compounds, and compounds identified by such methods
(example 17).  Patent Docs continues the discussion of these examples, reviewing Examples 13 and 14 drawn to antibody technology.

Example 13 – Antibody to a Single Protein

Example 13 provides guidance for a single exemplary claim directed to an isolated antibody that binds to an isolated and structurally characterized antigen.  This Example is essentially identical to the prior guidance in the former written description guidelines (presented therein as Example 16).  Nevertheless, the single claim presented in the new training materials recites:

Claim 1:  An isolated antibody capable of binding to antigen X.

The fact pattern of this example states that the specification discloses that "antigen X" was isolated from HIV and is useful for detection of HIV infection.  The specification describes purification of antigen X by gel filtration and discloses its amino acid sequence.  The specification also discloses that antigen X is a 55 kDa monomer, has no disulfide bonds, and has a slightly acidic pI.  While the hypothetical specification discusses antibodies that specifically bind to antigen X and states such antibodies can be used in immunoassays to detect HIV, the specification lacks a working or prophetic example of an antibody that binds to antigen X.  Nevertheless, given the level of skill and knowledge in the art of antibodies at the time the application was filed, production of antibodies against a well-characterized antigen was routine, and therefore the specification satisfies the written description requirement of § 112, first paragraph, with respect to the full scope of claim 1.

While the example fails to provide a specific filing date for the specification, it cites to the 1976 reference of Elvin A. Kabat ("Structural Concepts in Immunology and Immunochemistry," 2nd Ed. (Holt, Rinehart and Winston)) to provide evidence of the knowledge in the art that antibodies can be generated from isolated antigens, that the various isotypes (IgG, IgA, IgM, IgD, and IgE) share certain physical, chemical, and biological properties, and that there is sequence variation in the variable and hypervariable regions of the antibody sequence.  Thus, even though the specification fails to describe (a) any partial physical or chemical properties (e.g., molecular weight, association constant); (b) a partial structure of the claimed antibody by sequence, reference to a deposit, or in the drawings; (c) any functional correlation of antibody structure to binding activity to antigen X; and (d) any method for making an antibody that binds antigen X, the production of such antibodies is so conventional that the amount of disclosure present in this specification is adequate to demonstrate possession of the claimed antibody.

Example 14 – Antibodies to a Genus of Proteins

Example 14 is based on the fact pattern of the 2004 Federal Circuit case, Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004), and provides guidance for three exemplary claims directed to antibodies that bind to "Protein X" which was isolated from murine tissue and has been structurally characterized.  This Example is new relative to the prior written description training materials.  The three presented claims in this Example recite:

Claim 1:  A monoclonal antibody that binds Protein X.

Claim 1:  The antibody of claim 1 which binds murine Protein X.

Claim 3:  The antibody of claim 1 which binds human Protein X.

The fact pattern of this example states that the specification describes a monoclonal antibody that specifically binds to Protein X isolated from murine tissue, and protocols for producing anti-Protein X antibodies.  Protein X is disclosed as being located on the surface of certain immune cells and is asserted to be useful for treating immune disorders involving cell signaling.  The specification describes purification of murine Protein X and discloses its amino acid sequence.  The specification does not disclose any physical or chemical property for Protein X from any other species (e.g., no disclosure of molecular weight or cross-reactivity of human Protein X with anti-murine Protein X antibodies, and no sequence information for Protein X from any species other than mouse).  The specification does state that human Protein X is expected to have the same in vivo function as murine Protein X, and that antibodies to human Protein X will be useful for treating immune disorders involving cell-to-cell signaling.

Not surprisingly, the written description requirement for claim 2 above is completely satisfied by the disclosure in the specification, essentially for the same reasons provided in Example 13 (adequate description of the purified antigen satisfies written description for antibodies which bind the purified antigen).

As to claim 3, the lack of any physical or chemical description of an antibody that binds human Protein X, along with the lack of any physical or chemical description of human Protein X leads to the conclusion that written description is not satisfied for this claim.  As detailed in the analysis, the specification and prior art fail to provide any evidence that the disclosed properties of murine Protein X are predictive of the properties of human Protein X.  Further, the disclosure of human Protein X in the specification is purely functional and fails to provide any correlation to physical and chemical properties.  As stated in the materials, "Claim 3 is directed to an unknown that is identified only by reference to another unknown."

Similarly, the specification fails to provide written description for the full scope of claim 1, because the claim relates generically to many species of monoclonal antibodies that specifically bind to Protein X from any species.  While the specification adequately describes murine Protein X and therefore an antibody that binds murine Protein X, it fails to provide any physical or chemical description of Protein X from any other organism, and fails to describe a method of making an antibody that binds non-murine Protein X without first having the particular non-murine Protein X in hand.  Thus, because claim 1 is generic to antibodies to Protein X from a variety of organisms, and the specification fails to describe anything other than murine Protein X, claim 1 does not satisfy the written description requirement.  The analysis notes, without further clarification, that if any evidence was presented that murine Protein X was representative of the genus of Protein X molecules from other species, it is possible that claim 1 could meet the written description requirement.

For additional information on this topic, please see:

• "ESTs & Partial Protein Structures," May 8, 2008
• "DNA Hybridization & Percent Identity," May 6, 2008

    By Donald Zuhn —

Last month, the U.S. Patent and Trademark Office announced that it had updated the training materials to be used by examiners in the examination of patent applications for compliance with the written description requirement of 35 U.S.C. § 112, first paragraph.  The revised training materials supersede and replace the previous set of training materials issued by the Patent Office in 1999.  The new training materials provide seventeen examples, of which fourteen are specifically related to biotech inventions.  In particular, the biotech-specific examples address expressed sequence tags (ESTs) (example 4), a partial protein structure (example 5), DNA hybridization (example 6), allelic variants (example 7), bioinformatics (example 8), protein variants (example 9), a product claimed by its function (example 10), a polynucleotide or polypeptide sequence sharing percent identity with another sequence (example 11), antisense oligonucleotides (example 12), antibodies to a single protein (example 13), antibodies to a genus of proteins (example 14), a genus with widely varying species (example 15), a process claim where novelty resides in the process steps (example 16), and methods of using compounds claimed by functional limitations, methods of identifying compounds, and compounds identified by such methods (example 17).  Patent Docs will discuss these examples in a series of articles.  Today, we address examples 4 and 5.

Example 4

Example 4 concerns claims that are directed to an expressed sequence tag (EST), which the training materials define as a cDNA that corresponds to only part of a protein-encoding open reading frame (ORF).  The example is divided into two sections:  one that discusses the effect of open transitional language (example 4A), and one that discusses the effect of closed transitional language (example 4B).  The first section of this example provides a single exemplary claim:

Claim 1:  An isolated DNA comprising SEQ ID NO: 16.

Because this claim uses "open" transitional language (i.e., recites a DNA comprising the recited sequence), the claim encompasses a genus of DNAs in which additional DNA sequences may be attached to either end of the DNA sequence of SEQ ID NO: 16.  The claimed genus would thus include the full-length gene of which the DNA sequence of SEQ ID NO: 16 was a part.  Nevertheless, because the DNA sequence of SEQ ID NO: 16 is a structural feature common to all members of the genus, and the exemplary specification discloses the complete sequence of SEQ ID NO: 16, the specification satisfies the written description requirement with respect to claim 1.  It is important to note, however, that while the above claim would not be rejected under 35 U.S.C. § 112, first paragraph, it would most likely be rejected for failing to comply with the utility requirement of 35 U.S.C. § 101 (see Example 9 of the Revised Interim Utility Guidelines Training Materials).

The second section of Example 4 provides two exemplary claims:

Claim 1:  An isolated nucleic acid comprising SEQ ID NO: 1.

Claim 2:  An isolated nucleic acid consisting of SEQ ID NO: 1.

Because claim 2 uses "closed" transitional language (i.e., recites a nucleic acid consisting of the recited sequence), this claim only encompasses a single species.  Moreover, the exemplary specification discloses the complete sequence of this species.  Thus, the specification satisfies the written description requirement with respect to claim 2.  The analysis of claim 1 in Example 4B is identical to that of claim 1 in Example 4A, and therefore, because the exemplary specification of Example 4A satisfies the written description requirement with respect its claim 1, the exemplary specification of Example 4B likewise satisfies the written description requirement with respect its claim 1.

Example 5

Example 5 concerns claims directed to partial protein structures.  According to the training materials, Example 5 is based on In re Wallach, 378 F.3d 1330 (Fed. Cir. 2004).  This example provides two exemplary claims:

Claim 1:  An isolated protein comprising Protein A,
    wherein said Protein A includes the amino acid sequence of SEQ ID NO: 1 in the N-terminal portion of the protein, and has the same ability to bind to and activate Protein X as Protein A from human urine, and
    wherein said Protein A is purified by subjecting a crude protein recovered from a dialyzed concentrate of human urine to affinity chromatography on a column of immobilized Protein X, and elutes from a reversed-phase HPLC column as a single peak in a fraction corresponding to about 31% acetonitrile and shows a molecular weight of about 22 kDa when measured by SDS-PAGE under reducing conditions.

Claim 2:  An isolated DNA comprising a DNA that encodes Protein A,
    wherein said Protein A includes the amino acid sequence of SEQ ID NO: 1 in the N-terminal portion of the protein, and has the same ability to bind to and activate Protein X as Protein A from human urine, and
    wherein said Protein A is purified by subjecting a crude protein recovered from a dialyzed concentrate of human urine to affinity chromatography on a column of immobilized Protein X, and elutes from a reversed-phase HPLC column as a single peak in a fraction corresponding to about 31% acetonitrile and shows a molecular weight of about 22 kDa when measured by SDS-PAGE under reducing conditions.

According to the training materials, the exemplary specification discloses a sequence of 10 amino acids (SEQ ID NO: 1) that corresponds to the amino-terminal end of Protein A, but does not disclose the complete sequence of Protein A.  The training materials also note, however, that the exemplary specification discloses other relevant identifying characteristics of Protein A (e.g., its ability to bind and activate Protein X, its approximate molecular weight, and the concentration of acetonitrile at which Protein A will elute from a reverse phase HPLC column), as well as a method of isolating Protein A from urine and a working example in which Protein A was isolated from urine using this method.  In view of this disclosure, the training materials conclude that the specification satisfies the written description requirement with respect to claim 1.

Concerning claim 2, the training materials note that the exemplary specification fails to disclose either the complete nucleotide or complete amino acid sequence of Protein A.  In drawing a comparison between the isolated protein of claim 1 and the isolated DNA claim 2, the training materials state that while the exemplary specification provides relevant identifying characteristics for the protein, it does not provide sufficient relevant identifying characteristics for the DNA.  The training materials also state that because the exemplary specification fails to support even one species of DNA in the claimed genus, it is apparent that a representative number of species is not disclosed.  Thus, the training materials conclude that the specification fails to satisfy the written description requirement with respect to claim 2.

For additional information on this topic, please see:

• "DNA Hybridization & Percent Identity," May 6, 2008

    By Donald Zuhn —

Last month, the U.S. Patent and Trademark Office announced that it had updated the training materials to be used by examiners in the examination of patent applications for compliance with the written description requirement of 35 U.S.C. § 112, first paragraph.  The revised training materials supersede and replace the previous set of training materials issued by the Patent Office in 1999.  In the updated training materials, the Office explains that the revisions to the materials were necessitated by changes in both the case law and technology since the 1999 training materials were issued.  The Office also notes that to the extent that conflicts exist between the 1999 training materials and the new materials, the new materials will control.

Commenting on the new training materials, Commissioner for Patents John Doll stated that the materials "will improve the quality and consistency of patent examination, as well as provide guidance to practitioners for the drafting of patent applications and responses to examiners."  According to the Patent Office, the new materials are intended to assist patent examiners in applying the "Guidelines for Examination of Patent Applications Under the 35 U.S.C § 112, first paragraph ‘Written Description’ Requirement," which were originally published in the Federal Register on January 5, 2001, and which are now incorporated in the M.P.E.P. at § 2163.

The new training materials provide seventeen examples, of which fourteen are specifically related to biotech inventions.  In particular, the biotech-specific examples address expressed sequence tags (ESTs) (example 4), a partial protein structure (example 5), DNA hybridization (example 6), allelic variants (example 7), bioinformatics (example 8), protein variants (example 9), a product claimed by its function (example 10), a polynucleotide or polypeptide sequence sharing percent identity with another sequence (example 11), antisense oligonucleotides (example 12), antibodies to a single protein (example 13), antibodies to a genus of proteins (example 14), a genus with widely varying species (example 15), a process claim where novelty resides in the process steps (example 16), and methods of using compounds claimed by functional limitations, methods of identifying compounds, and compounds identified by such methods (example 17).  Patent Docs will discuss these examples in a series of articles.  Today, we address examples 6 and 11.

Example 6

Example 6 concerns claims that are directed to nucleic acid molecules that hybridize to a recited sequence.  This example provides three exemplary claims:

Claim 1:  An isolated nucleic acid that encodes a protein that binds to the NDG [newly-discovered growth factor] receptor and stimulates tyrosine kinase activity.

Claim 2:  An isolated nucleic acid that encodes a protein that binds to the NDG receptor and stimulates tyrosine kinase activity, and consists of the sequence set forth in SEQ ID NO: 1.

Claim 3:  An isolated nucleic acid that encodes a protein that binds to the NDG receptor and stimulates tyrosine kinase activity, wherein the nucleic acid hybridizes under highly stringent conditions to the complement of the sequence set forth in SEQ ID NO: 1.

According to the training materials, the specification, which discloses the nucleotide sequence of SEQ ID NO: 1, satisfies the written description requirement with respect to the full scope of claim 2.  However, because claim 1 encompasses a broad genus of isolated nucleic acids, and the specification fails to disclose any information about the structure or location of NDG receptor binding domains in the protein encoded by the nucleotide sequence of SEQ ID NO: 1, the specification fails to satisfy the written description requirement with respect to the full scope of claim 1.

Concerning claim 3, the training materials acknowledge that "nucleic acids that hybridize to the complement of SEQ ID NO: 1 must share many nucleotides in common with SEQ ID NO: 1," and therefore, that "[t]he disclosure of SEQ ID NO: 1 combined with the knowledge in the art regarding hybridization would put one in possession of the genus of nucleic acids that would hybridize under stringent conditions to SEQ ID NO: 1."  However, the training materials conclude that the specification fails to satisfy the written description requirement with respect to the full scope claim 3 because the specification does not disclose a recognized correlation between the structure of the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and its function, and without this correlation "those of ordinary skill in the art would not be able to identify without further testing which of those nucleic acids that hybridize to SEQ ID NO: 1 would also encode a polypeptide that binds to NDG receptor and stimulates tyrosine kinase activity."

Example 11

Example 11 concerns claims that are directed to a polynucleotide or polypeptide sequence that shares percent identity with another sequence.  The example is divided into two sections, one in which there is no art-recognized structure-function correlation for the claimed sequence (example 11A), and one in which there is an art-recognized structure-function correlation for the claimed sequence (example 11B).  The first section of this example provides two exemplary claims:

Claim 1:  An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2.

Claim 2:  An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2; wherein the polypeptide has activity X.

Despite the specification’s disclosure of only a single species encoding the polypeptide of SEQ ID NO: 2 (i.e., SEQ ID NO: 1), and the lack of any teaching in the specification regarding which amino acid residues in SEQ ID NO: 2 are tolerable to change, the training materials indicate that the specification satisfies the written description requirement with respect to the scope of claim 1.  According to the training materials, this is so because "[w]ith the aid of a computer, one of skill in the art could have identified all of the nucleic acids that encode a polypeptide with at least 85% sequence identity with SEQ ID NO: 2."  However, because the specification lacks any teaching as to which amino acid residues in SEQ ID NO: 2 can be changed while still retaining activity X, and the art lacks any recognized correlation between structure (SEQ ID NO: 2 domains) and function (activity X), the training materials indicate that the specification fails to satisfy the written description requirement with respect to the scope of claim 2.  This would seem to suggest that if claim 3 in Example 6 above were rewritten to exclude an activity limitation, claim 3 would satisfy the written description requirement, since a nucleotide sequence hybridizing under highly stringent conditions would be expected to encode a protein having a sequence identity that is greater than 85%.

The second section of Example 11 also provides two exemplary claims:

Claim 1:  An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2.

Claim 2. An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2; wherein the polypeptide has activity Y.

The only difference between the hypothetical specification of Example 11A and the hypothetical specification of Example 11B is that the latter identifies two domains that are critical to activity Y (i.e., a binding domain and a catalytic domain).  Not surprisingly, the training materials find that the specification satisfies the written description requirement with respect to the scope of claim 1 of Example 11B.  With respect to claim 2 of Example 11B, the training materials indicate that the specification, which now discloses two domains responsible for activity Y, satisfies the written description requirement.