Ex Parte Tryggvason et al

Patent Trial and Appeal Board

Jan 26, 2017

12725877 (P.T.A.B. Jan. 26, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/725,877 03/17/2010 Karl Tryggvason LCTI 2 00001US05 1130
27885 7590 01/26/2017
FAY SHARPE LLP
1228 Euclid Avenue, 5th Floor
The Halle Building
Cleveland, OH 44115
EXAMINER
TON, THAIAN N
ART UNIT PAPER NUMBER
1632
MAIL DATE DELIVERY MODE
01/26/2017 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KARL TRYGGVASON,
SERGEY RODIN, and ANNA DOMOGATSKAYA
Appeal 2016-001857
Application 12/725,877
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving a composition and
method for enabling self-renewal of pluripotent human stem cells grown in
vitro. The Examiner rejected the claims as anticipated, as obvious, as non-
statutory subject matter, and on the grounds of obviousness-type double
patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as the Biolamina AB (see
App. Br. 1).
Appeal 2016-001857
Application 12/725,877
Statement of the Case
Background
“A stem cell is an undifferentiated cell from which specialized cells
are subsequently derived. Embryonic stem cells possess extensive self­
renewal capacity and pluripotency with the potential to differentiate into
cells of all three germ layers” (Spec. 13). “[T]he development of
chemically defined and xeno-ffee culture environments for human
embryonic stem (hES) cells has been an important goal” (Spec. 17).
“The present disclosure is directed to the development of
compositions, such as extracellular matrices, and processes for using the
same, for culturing human stem cells in vitro in an undifferentiated state”
(Spec. 115).
The Claims
Claims 1—12 and 14—19 are on appeal. Claim 1 is representative and
reads as follows:
1. A composition for enabling self-renewal of pluripotent
human stem cells grown in vitro, comprising:
a substrate;
a coating comprising intact recombinant laminin-511
(LN-511 or laminin-10) and being devoid of both animal
proteins and feeder cells; and
a chemically defined medium that is devoid of feeder
cells and contains bFGF.
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The Issues
A. The Examiner rejected claims 1,2, 14, 15, and 17—19 under 35 U.S.C.
§ 102(b) as anticipated by Tryggvason ’4012 as evidenced by Doi3 (Final
Act. 6).
B. The Examiner rejected claims 1—12 and 14—19 under 35 U.S.C.
§ 103(a) as obvious over Beattie,4 Millipore,5 Kikkawa,6 and Ludwig7 (Final
Act. 7-10).
C. The Examiner rejected claims 1—12 and 14—19 under 35 U.S.C.
§ 103(a) as obvious over Miyazaki8 and Ludwig (Final Act. 10-11).
D. The Examiner rejected claims 1, 3, 5—12, 14, 16, 18, and 19 under
35 U.S.C. § 103(a) as obvious over Tryggvason ’401, Doi, and Ludwig
(Final Act. 11—13).
2 Tryggvason et al., WO 2008/084401 Al, published July 17, 2008
(“Tryggvason ’401”).
3 Doi et al., Recombinant Human Laminin-10 (a5flyl), 277 J. Biological
Chemistry 12741^18 (2002) (“Doi”).
4 Beattie et al., Activin A Maintains Pluripotency of Human Embryonic Stem
Cells in the Absence of Feeder Layers, 23 Stem Cells 489—95 (2005)
(“Beattie”).
5 Millipore catalog, Human Laminin (pepsinized) Purified Protein, Accessed
Feb. 24, 2009 (“Millipore”).
6 Kikkawa et al., Laminin isoforms differentially regulate adhesion,
spreading, proliferation, and ERK activation of f31 integrin-null cells, 300
Experimental Cell Research 94—108 (2004) (“Kikkawa”).
7 Ludwig et al., Derivation of human embryonic stem cells in defined
conditions, 24 Nature Biotechnology 185-7 (2006) (“Ludwig”).
8 Miyazaki et al., Recombinant human laminin isoforms can support the
undifferentiated growth of human embryonic stem cells, 375 Biochemical
Biophysical Research Communications 27-32 (2008) (“Miyazaki”).
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Application 12/725,877
E. The Examiner rejected claims 1, 2, 4—6, 9, 11, 13—15, and 17—19 on
the ground of nonstatutory double patenting as being unpatentable over
claims 1—3 of US 8,722,405 (Final Act. 14—15).
F. The Examiner rejected claims 1^4 under 35 U.S.C. § 101 as directed
to a judicial exception (Ans. 3—7).
A., C., D. 35 U.S.C. § 102(b) and 103(a) over Tryggvason ’401 or
Miyazaki
Because the same priority issue is dispositive for these four rejections,
we will consider them together.
The Examiner finds “the priority document (11/969,620) does not
have support for the phrase ‘a coating comprising intact laminin’ (claim 1);
or ‘a substrate comprising full-length recombinant laminin’ (claim 5)” (Ans.
7). In particular, the Examiner finds the “phrase laminin can encompass any
number of fragments of laminin, which may include full-length or intact
laminin, but does not exclude the possibility of fragments that are not full
length or intact” (Ans. 8).
Appellants contend
the ’620 application provides at least implicit support for a
laminin that is “intact” or “full-length”. Initially, paragraph
[0008] of the ’620 application describes laminins as being large
transparent extracellular matrix proteins that are composed of
three chains. Throughout the text, reference is made only to
“laminins”, with no reference to various parts of the laminin.
. . . Finally, claim 1 of the ’620 application refers to “a coating
comprising laminin 332 or laminin 511, or their functional
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domains.” The phrase “or their functional domains” also
emphasizes that “laminin” refers to the complete protein.
(App. Br. 4-5).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner’s conclusion that the Specification of US
11/969,620 fails to provide descriptive support for the phrase “intact
laminin” or “full-length laminin” in claims 1 and 5?
Findings of Fact
1. The Specification of US 11/969,620 teaches “[ljaminins are
large trimeric extracellular matrix proteins that are composed of alpha, beta,
and gamma chains. There exist five different alpha chains, three beta chains
and three gamma chains that in mouse and human tissues have been found in
at least fifteen different combinations” (US 11/969,620 Spec. 1 8; cf. US
60/883,406 1 6).
2. The Specification of US 11/969,620 teaches “[tjhese molecules
are termed laminin-1 to laminin-15 based on their historical discovery, but
an alternative nomenclature describes the isoforms based on their chain
composition, e.g. laminin-111 (laminin-1) that contains alpha-1, beta-1 and
gamma-1 chains” (US 11/969,620 Spec. 1 8; cf. US 60/883,4061 6).
3. The Specification of US 11/969,620 teaches:
96-well tissue cell culture plates (Sarstedt) were coated
overnight at 4°C by sterile solutions of extracellular matrix
proteins: murine laminin-111 (Invitrogen), human recombinant
laminin-332, human recombinant laminin-411 (Kortesmaa, J.,
Yurchenco, P., and Tryggvason, K. (2000); Recombinant
laminin-8 (alpha(4)beta(l)gamma(l)). Production, purification,
and interactions with integrins. J Biol Chem 275, 14853-
14859, U.S. Patent 6,638,907), human recombinant laminin-
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511 (Doi, M., Thyboll, J., Kortesmaa, J., Jansson, K.,
livanainen, A., Parvardeh, M., Timpl, R., Hedin, U.,
Swedenborg, J., and Tryggvason, K. (2002); Recombinant
human laminin-10 (alpha5betalgammal); Production,
purification, and migration-promoting activity on vascular
endothelial cells. J Biol Chem 277, 12741-12748; U.S. Patent
6,933,273)
(US 11/969,620 Spec. 131; cf. US 60/883,406 122).
4. The Specification of US 11/969,620 claims “1. A composition
for enabling proliferation of pluripotent stem cells grown in vitro on a
coating comprising laminin 332 (laminin-5) or laminin 511 (laminin-10), or
their functional domains” (US 11/969,620 Spec. 15, claim 1; cf. US
60/883,406 12, claim 1).
Principles of Law
Under 35 U.S.C. § 120, “in a chain of continuing applications, a claim
in a later application receives the benefit of the filing date of an earlier
application so long as the disclosure in the earlier application meets the
requirements of 35 U.S.C. § 112,11, including the written description
requirement, with respect to that claim.” Tech. Licensing Corp. v. Videotek,
Inc., 545 F.3d 1316, 1326 (Fed. Cir. 2008).
Analysis
We find that Appellants have the better position. The Specification of
US 11/969,620 is reasonably interpreted as referring to laminin proteins
composed of intact, full-length alpha, beta, and gamma chains for two
reasons. First, the original claim expressly recites particular laminins “or
their functional domains” (FF 4). The most reasonable interpretation of “or
their functional domains” is that the original claim is drawn to particular
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laminins that are full-length and intact and may also encompass laminins
that are not full-length and intact, but rather are composed of “functional
domains” of the laminins.
Second, the description in paragraph 31 of the actual laminins used in
examples (FF 3) cites to the use of recombinant laminins produced in several
papers published in the Journal of Biological Chemistry. A review of those
papers shows that the laminins produced in those papers are full-length and
intact, further supporting the conclusion that the Specification has “set forth
enough detail to allow a person of ordinary skill in the art... to recognize
that the inventor invented what is claimed.” University of Rochester v. G.D.
Searle & Co., 358 F.3d 916, 928 (Fed. Cir. 2004).
We therefore reverse the Examiner’s rejections that rely upon either
Tryggvason ’401 or Miyazaki, because these references are not prior art
relative to the priority date of the US 11/969,620 priority document filed
Jan. 4, 2008, and provisional US 60/883,406, filed Jan. 4, 2007, both of
which reasonably provide descriptive support for full-length, intact laminins.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the Specification of US 11/969,620 fails to provide descriptive support
for the phrase “intact laminin” or “full-length laminin” in claims 1 and 5.
B. 35 U.S.C. § 103(a) over Beattie, Millipore, Kikkawa, and Ludwig
The Examiner finds “Beattie teach[es] culturing human ES cells . . .
on laminin in DSR medium containing 50 ng/ml of recombinant activin A
and 50 ng/ml recombinant KGF and 10 mM NIC” (Final Act. 8). The
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Examiner acknowledges that Beattie does not teach “the medium is a
chemically defined medium that is devoid of feeder cells” (id.).
The Examiner finds “Ludwig teach the development of TeSRl, a
serum-free, animal product-free medium that supports culture and derivation
of human ES cells” (Final Act. 9). The Examiner finds the ordinary artisan
“would have been motivated to use the TeSRl media because it would
prevent contamination from animal products” (Final Act. 10).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner’s conclusion that Beattie, Millipore, Kikkawa,
and Ludwig render claims 1 and 5 obvious?
Findings of Fact
5. Beattie teaches
passage 43 hESCs [human embryonic stem cells] were cultured
on dishes coated with laminin ... in the presence of CM
[conditioned medium] from mEFs [mouse embryonic feeder
layers] supplemented with 10 ng/ml basic fibroblast growth
factor ... or on laminin in DSR [serum replacement] medium
containing 50 ng/ml human recombinant activin A, 50 ng/ml
human recombinant KGF (both from PreproTech), and 10 mM
NIC
(Beattie 490, col. 1).
6. Beattie teaches “[r]emoval of activin from the growth medium
resulted in the rapid change in cell morphology to a differentiated
phenotype” (Beattie 492, col. 1).
7. Beattie teaches “[t]hese data show that maintenance of hESCs
in medium containing activin A allows the maintenance of pluripotency
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without the need for coculture with other foreign or human cells” (Beattie
495, col. 1).
8. Beattie teaches “[i]n contrast, when activin was removed from
the culture for 1 week, the level of expression was reduced to 3.9%” (Beattie
492, col. 1).
9. Ludwig teaches “feeder-independent human ES cell culture that
includes protein components solely derived from recombinant sources or
purified from human material. We describe the derivation of two new
human ES cell lines in these defined culture conditions” (Ludwig, abstract).
10. Ludwig teaches “a combination of collagen IV, fibronectin,
laminin and vitronectin supported robust, long-term proliferation of human
ES cells in TeSRl” (Ludwig 186, col. 1).
11. Ludwig teaches that “TeSRl containing all five factors (bLGL,
LiCl, GABA, pipecolic acid and TGLP) is sufficient to support feeder-
independent human ES cell culture as well as or better than fibroblast-
conditioned medium” (Ludwig 186, col. 2).
12. Ludwig teaches:
Unlike previous human ES cell culture media that included
proprietary, poorly defined serum components with undisclosed
formulations, all TeSRl components are disclosed, and thus
should serve as a starting point for further optimization by other
investigators. One of the areas that needs improvement is the
matrix, as the purified human matrix components are expensive
and provide a potential route of contamination by human
pathogens.
(Ludwig 186, col. 2).
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Principles of Law
“The prior art’s mere disclosure of more than one alternative does not
constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Analysis
We agree with the Examiner that the claims are obvious over the
combination of Beattie, Millipore, Kikkawa, and Ludwig. In particular,
Beattie teaches a composition that comprises a substrate, dishes, with a
laminin coating devoid of other proteins and feeder cells and a medium that
containing bFGF (FF 5). As the Examiner acknowledges, Beattie does not
teach a defined chemical medium devoid of feeder cells (see Final Act. 8).
However, Ludwig teaches defined chemical media for growth of ES cells
that includes bFGF (FF 9, 11) grown on a matrix containing laminin and
other proteins (FF 10).
We agree that the ordinary artisan, interested in improving the
composition of Beattie to use defined serum components, would have had
reason to employ a serum composition as suggested by Ludwig (FF 12).
Appellants contend that “Ludwig’s medium does not contain activin
A, and thus Beattie would not have used Ludwig’s medium” (App. Br. 7).
Appellants contend “Beattie actually teaches away from Ludwig, as Beattie
teaches that media conditions excluding activin would result in differentiated
cells, and Ludwig’s medium does not contain activing[]” (id.).
We do not find this argument persuasive because claims 1 and 5
utilize the open transitional language “comprising” and are therefore open to
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chemically defined medium that comprise bFGF, all of the components
disclosed in Ludwig, and purified recombinant activin A disclosed by
Beattie. That is, to the extent that Beattie suggests activin A is a required
element in the growth medium, Ludwig does not teach away from inclusion
of this purified protein and claims 1 and 5 do not exclude the presence of
activin A. Appellants do not identify, and we do not find, any teaching in
either Beattie or Ludwig criticizing, discouraging, or discrediting the use of
defined medium that contains activin A along with the specific components
disclosed by Ludwig (FF 11).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Beattie, Millipore, Kikkawa, and Ludwig render claims 1 and 5 obvious.
E. Double Patenting
Appellants stated “Applicants do not appeal this rejection, and will
overcome this rejection by submitting a Terminal Disclaimer” (App. Br. 8).
We therefore summarily affirm the obviousness-type double patenting
rejection. See Manual of Patent Examining Procedure § 1205.02 (“If a
ground of rejection stated by the examiner is not addressed in the appellant’s
brief, that ground of rejection will be summarily sustained by the Board.”)
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F. 35 U.S.C. § 101
The Examiner finds:
The claim(s) are directed to a composition of matter (Step 1), a
composition comprising 1) a substrate; 2) a coating comprising
intact recombinant laminin-511; 3) chemically defined medium
and 4) bFGF. Further embodiments recite that the medium
comprises growth factors (claim 2); human albumin (claim 3).
This composition of matter is directed to a natural phenomenon
(Ans. 5). The Examiner finds “the limitations of the claims do not impose
limits on the claim scope to render the claims markedly different in structure
from a naturally occurring product” (Ans. 6).
Appellants contend “[tjhese methods can only be practiced due to the
non-naturally occurring elements, i.e. the substrate, the non-natural coating
formed from the laminin, and the chemically defined medium. Thus, the
claims, which contain additional elements, amount to ‘significantly more’
than the judicial exception itself’ (Reply Br. 3). Appellants contend that
claim 1 is quite similar to claim 5 of Example 17 of Appendix 2
of the July 2015 Update: Subject Matter Eligibility (i.e.
Example 9 of the Examples: Nature-Based Products issued on
December 16, 2014).. . claim 5 was found to be eligible
because the combination of the cells in the scaffold confined the
claim to a particular useful application (repair of cardiac tissue),
and improved the technology.
(Reply Br. 3—4).
We find that Appellants have the better position. In Example 9 of the
2014 Guidance for nature-based products,9 claim 1 is drawn to an isolated
9 https://www.uspto.gov/patents/law/exam/mdc_examples_nature-
based_products.pdf 1—17 (“2014 Guidance”).
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cell while claim 5 is drawn to a combination of the cells with a scaffold
(2014 Guidance 14). The 2014 Guidance states the
recitation of the biocompatible three-dimensional scaffold in
combination with the pacemaker cells is not required for
growing or using the cells, because the cells can be grown or
used in other containers, and is not recited at a high level of
generality. The addition of the pacemaker cells to the
scaffold confines the claim to a particular useful application
of the scaffold.
(2014 Guidance 15).
The instant claims are similar to Example 9 because the pluripotent
human stem cells are not recited as growing on any substrate, but rather a
particular substrate coated with intact recombinant laminin-511 along with a
chemically defined medium (see claims 1 and 5).
We agree with Appellants that the claimed combination results in
something “significantly more” than the naturally occurring products. This
is not a simple combination of known rhizobium bacterial inoculant
components as in Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S.
127, 132 (1948). Nor is this drawn to a specific biological product such as
the nucleic acid at issue in Ass ’n for Molecular Pathology v. Myriad
Genetics, Inc., 133 S. Ct. 2107, 2116-2117 (2013).
Instead, the claims require a purified natural product, laminin-511
coated onto a substrate without other components, and also requires a
chemically defined medium solution that comprises bFGF but lacks feeder
cells. This claimed product, not naturally occurring, enables pluripotent
stem cells to grow in vitro without differentiation, thereby adding something
“significantly more” than the simple combination of components which, if
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simply mixed together, would not necessarily result in a composition
capable of supporting the growth of pluripotent stem cells.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Beattie, Millipore, Kikkawa, and Ludwig. Claims
2—12 and 14—19 fall with claim 1.
We affirm the rejection of claims 1, 2, 4—6, 9, 11, 13—15, and 17—19
on the ground of nonstatutory double patenting as being unpatentable over
claims 1-3 of US 8,722,405.
We reverse the rejection of claims 1,2, 14, 15, and 17—19 under
35 U.S.C. § 102(b) as anticipated by Tryggvason ’401 as evidenced by Doi.
We reverse the rejection of claims 1—12 and 14—19 under 35 U.S.C.
§ 103(a) as obvious over Miyazaki and Ludwig.
We reverse the rejection of claims 1, 3, 5—12, 14, 16, 18, and 19 under
35 U.S.C. § 103(a) as obvious over Tryggvason ’401, Doi, and Ludwig.
We reverse the rejection of claims 1^4 under 35 U.S.C. § 101 as
directed to a judicial exception.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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