By James DeGiulio —

This
week, Fate Therapeutics of San Diego, CA was issued a Notice
of Allowance for U.S. Application No. 10/997,146 (U.S. Patent Application Publication No. 2008/0280362), titled "Methods
for Reprogramming Somatic Cells."  With a priority date of November 26, 2003, the application is believed
to contain the earliest allowed claims in the United States for induced pluripotent
stem cell technology.  Upon
issuance, the invention by Rudolf Jaenisch, M.D. (below left), founding member of the Whitehead
Institute for Biomedical Research and scientific founder of Fate Therapeutics,
will cover methods for generating pluripotent stem cells and compositions for
identifying agents that enable the reprogramming of human somatic cells.

The
application first describes the need for alternative methods of generating
human pluripotent cells without using embryos, oocytes, or nuclear transfer
technology and how reprogrammed somatic cells can enable autologous cell
therapy, including the treatment of neurological diseases.  The application
describes novel methods of reprogramming somatic cells by introducing certain
pluripotency genes, such as Oct4, Nanog, or Sox2.  The application further
covers compositions used in screening for agents to generate these pluripotent
cells, including genes, classes of small molecules, or pluripotency
proteins.  The application's lone Example describes
the generation of a transgenic mouse by integration of an inducible Oct-4 gene
and the resulting enhanced stem cell populations.

After
a series of amendments, including an examiner's amendment, twelve total claims
were allowed, including three independent claims:

17.  A primary somatic cell comprising in its genome a first endogenous pluripotency
gene operably linked to DNA encoding a first selectable marker in such a manner
that expression of the first selectable marker substantially matches expression
of the first endogenous pluripotency gene, wherein the cell additionally
comprises an exogenously introduced nucleic acid encoding a pluripotency
protein and operably linked to at least one regulatory sequence, wherein the
endogenous pluripotency gene is a gene that is expressed in a pluripotent
embryonic stem cell, is required for the pluripotency of the embryonic stem
cell, and is downregulated as the embryonic stem cell differentiates, and
wherein the pluripotency protein is a protein expressed in a pluripotent
embryonic stem cell, and is downregulated as the embryonic stem cell
differentiates.

36.  A primary somatic cell comprising in its genome a first endogenous pluripotency
gene operably linked to DNA encoding a first selectable marker in such a manner
that expression of the first selectable marker substantially matches expression
of the first endogenous pluripotency gene, wherein the first endogenous
pluripotency gene encodes Oct4 or Nanog, and wherein the cell additionally
comprises an exogenously introduced nucleic acid encoding Oct4, Nanog, or Sox2
and operably linked to at least one regulatory sequence.

38.  A composition comprising:
    (i)  a primary somatic cell comprising in its genome a first endogenous pluripotency
gene operably linked to DNA encoding a first selectable marker in such a manner
that expression of the first selectable marker substantially matches expression
of the first endogenous pluripotency gene, and additionally comprising an
exogenously introduced nucleic acid encoding Oct4, Nanog, or Sox2 and operably linked
to at least one regulatory sequence; and
    (ii)  a candidate agent of interest with respect to its potential to reprogram a
somatic cell, wherein the first endogenous pluripotency gene encodes Oct4 or
Nanog.

James DeGiulio has a doctorate in molecular biology and genetics from Northwestern University and is a third-year law
student at the Northwestern University School of Law.  Dr. DeGiulio
was a member of MBHB's 2009 class of summer associates, and he can be contacted at degiulio@mbhb.com.