Ex Parte Li et al

Patent Trial and Appeal Board

Sep 20, 2018

13341239 (P.T.A.B. Sep. 20, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/341,239 12/30/2011
20350 7590 09/24/2018
KILPATRICK TOWNSEND & STOCKTONLLP
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
UNITED ST A TES OF AMERICA
Gang Li
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
80015-826649 8740
EXAMINER
BABIC, CHRISTOPHER M
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
09/24/2018 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ipefiling@kilpatricktownsend.com
KTSDocketing2@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GANG LI, YUK WAI LEE, and PO YING LAU1
Appeal2017-010493
Application 13/341,23 9
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN G. NEW, and
ELIZABETH A. LA VIER, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state that the real party-in-interest is The Chinese University of
Hong Kong. App. Br. 3.
Appeal2017-010493
Application 13/341,239
SUMMARY
Appellants file this appeal under 35 U.S.C. § I34(a) from the
Examiner's Final Rejection of claims 8, 10, and 12-23 as unpatentable under
35 U.S.C. § I03(a) as being obvious over the combination of Lim et al., (US
2012/0107413 Al, May 3, 2012) ("Lim"), K.K. Jha et al., SV40-Mediated
lmmortalization, 245 EXPER. CELL REs. 1-7 ( 1998) ("Jha"), K. Nishioka et
al., Immortalization of Bone Marrow-Derived Human Mesenchymal Stem
Cells by Removable Simian Virus 40T Antigen Gene: Analysis of the Ability
to Support Expansion of Cord Blood Hematopoietic Progenitor Cells, 23(4)
INT. J. ONCOL. 925-32 (2003) ("Nishioka"), M. Cihova et al., Stem Cell
Based Cancer Gene Therapy, 8 MOL. PHARMACEUTICS 1480-1487 (2011)
("Cihova"), Nelson (US 9,434,925 B2, September 6, 2016) ("Nelson"), and
Suh et al. (US 2008/0241115 Al, October 2, 2008) ("Suh"). 2
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to cell-mediated gene therapy for
cancer using mesenchymal stem cells ("MSC") expressing a suicide gene.
The MSC are administered to a subject having a tumor and are allowed to
migrate to the tumor site, and then the subject is administered a prodrug.
2 Claims 10, 13, 14, and 20 were also rejected as unpatentable under 35
U.S.C. § 112, second paragraph, as being indefinite. Final Act. 2. That
rejection has been withdrawn by the Examiner. Ans. 9.
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Expression of the suicide gene by the MSC at the tumor site converts the
prodrug to a drug that is lethal to cells of the tumor. Abstr.
REPRESENTATIVE CLAIM
Claim 8 is representative of the claims on appeal and recites:
8. A human fetal mesenchymal stem cell, which is pleiotropic,
nonembryonic, bone marrow derived, and immortalized by SV 40 large
and small T-antigen, and which recombinantly expresses a suicide
gene.
App. Br. 11.
ISSUES AND ANALYSES
We are persuaded by, and expressly adopt, the Examiner's findings,
reasoning, and conclusions establishing that Appellants' claims are prima
facie obvious over the cited prior art. We address the arguments raised by
Appellants below.
Issue 1
Appellants argue that the Examiner erred because the claimed
mesenchymal stem cell possesses surprising, unexpected properties. App.
Br. 6.
Analysis
Appellants argue that the Examiner mischaracterizes the
therapeutically effective doses of mesenchymal stem cells ("MS Cs") that are
disclosed by the cited prior art, and that such mischaracterization obscures
the difference between the allegedly unexpected and surprising effectiveness
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of Appellants' claimed MS Cs and the effectiveness of the MSCs of the cited
prior art. App. Br. 6. According to Appellants, the lowest therapeutically
effective dose reported by Nelson was 2.5 x 107 MSCs/kg body mass, the
dose repeated once every six days for 36 days. Id. (citing Nelson 30, 34,
35). Appellants assert that the 1 x 105 MSCs/kg body mass dosage cited by
the Examiner is taught only as an aspirational goal but not taught has having
been achieved by Nelson as a whole. Id.
Appellants acknowledge that Suh teaches an effective reduction in
tumor size using a dose of approximately 2 x 106 MSCs/kg body mass. App.
Br. 6 (citing Suh ,r,r 75-77). Appellants point out, however, that Suh
achieved this effective dosage by injecting a mixture of MSCs and the tumor
cells, and then detected growth inhibition of those tumor cells. Id.
Appellants argue that a person of ordinary skill in the art would have
understood that the apparent effectiveness of Suh's MSCs in this co-
injection method is greatly increased by injecting the target tumor cells and
MSCs together in a mixture in which tumor cells and MSCs are in direct
contact with each other. Id. Appellants assert that this is in contrast to the
systemic delivery method by which Appellants' MS Cs were assessed for
efficacy, because MSC migration to the tumor site is required after systemic
injection. Id. Appellants contend that the effectiveness of Suh's co-injected
MSCs is not directly comparable with the effectiveness of Appellants'
claimed MSCs which were administered by systemic injection. Id.
Appellants state that their claimed MSCs are therapeutically effective
at a dose of 11 x 106 MSCs/kg body mass when systemically injected, which,
Appellants note, is half of the effective dose reported by Suh. App. Br. 7.
Appellants argue that this effective dose is demonstrated by the experimental
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data submitted as Exhibit B of Appellants' response of February 28, 2013.
Experimental details regarding Exhibit B, are further provided by the
Declaration of Dr. Gang Li of October 8, 2013 (the "Li Declaration"). 3 Id.
(citing, e.g., Li Deel. ,r,r 8-10). Appellants point to Dr. Li's statement that it
is both significant and surprising to achieve a therapeutic benefit at such a
low dose. Id. ( citing Li Deel. ,r,r 8, 11 ). Notably, Appellants assert, Dr. Li
testifies that, to his knowledge and in view of the cited references, such a
low effective dose had never been achieved prior to the present invention.
Id. ( citing Li Deel. ,r 8).
Appellants also note that the Examiner finds that Appellants'
Specification teaches only an example administering 1 x 106 MSCs/mouse.
App. Br. 7 (citing Final Act. 6). Appellants contend, however, that this
single disclosure of the Specification does not preclude the use of
unexpected results for overcoming an obviousness allegation. Id.
Appellants argue that evidence of unexpected results can be used to
overcome a prima facie case of obviousness where the unexpected result is
not disclosed in the application as filed. Id. (citing Genetics Institute, LLC v.
Novartis Vaccines & Diagnostics, Inc., 655 F.3d 1291, 1307 (Fed. Cir.
2011) ). Appellants therefore contend that their claimed MS Cs exhibit
3 Dr. Gang Li, one of the inventors of record of the instant application,
received a D. Phil. from the University of Oxford Medical School in 1997
and is currently, inter alia, Professor at the Department of Orthopaedics
and Traumatology at The Chinese University of Hong Kong (CUHK). Li
Deel. ,r,r 2-3. Based upon his stated qualifications, we recognize Dr. Li's
fitness to render an expert opinion.
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surprising and unexpected properties sufficient to overcome the Examiner's
prima facie case of obviousness. Id.
The Examiner responds that Appellants' Specification teaches a single
example of administering at least 1 x 106 cells of SV 40-TK-GFP transduced
MSCs/mouse via intra-tumor delivery to obtain an anti-tumor effect. Ans. 8
( citing Spec. ,r 100). The Examiner finds that, because a specific dosage of
cells is not recited by the Appellants claims, and Appellants' support for the
superior effective dosage comes only from Appellants' arguments and from
a previous affidavit that indicates that the lowest effective therapeutic dose
of 1 x 106 cells/kg body mass, Appellants' argument that the cells show
unexpected results is not persuasive. Id.
Furthermore, the Examiner finds the low dosages that Appellants
allege are surprising in their efficacy (i.e., 1 x 106 cells/kg body mass) are
not surprising and/or unexpected in view of the cited prior art references.
Ans. 8. The Examiner points to Nelson, which teaches that genetically
modified MS Cs are therapeutically effective at dosages of 1 x 105 cells/kg
body mass. Id.
We agree with the Examiner. Appellants' Specification discloses that:
"[T]he effective dose of MSC in human subjects may be of the order of 1 x
10 7 cells per kg [body mass], or between O .2 x 10 7 and 5 x 10 7 for systemic
administration, scaled down appropriately if given locally." Spec. 10.
Further, the Specification discloses, in Example 7, a dosage of 1 x 106
MSCs/mouse. Given a mean body mass of 22.5g/mouse (see Li Deel., Ex.
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B), this dosage appears to correspond to approximately 4.4 x 107 MS Cs/kg
body mass.
Appendix B to the Li Declaration states that: "Nude mice bearing
either Luc-GFP-DU145 or Luc-GFP-PC3 were subjected to the treatment of
either GCV (30 mg/kg, i.p.), Dox (1.5 mg/kg, i.p.) or SV40-TK-htBMSCs (1
x 106 cells/kg, i.v.) followed by GCV (30 mg/kg, i.p.)." Li Deel. Ex. B 1
( emphasis added). Exhibit B also discloses administration of immortalized
TK-hffiMSCs at 5 x 106 MSCs/kg body mass. 4 Id. at 4.
Nelson teaches that: "This invention also provides a method for
treating a human subject afflicted with a pancreatic tumor comprising
introducing into the subject's bloodstream from about lxl05 to about lxl09
cells/kg body weight [sic] of genetically modified CD34- stem cells .... "
Nelson col. 2, 11. 14--18. Nelson also teaches that:
In this invention, the therapeutically effective number of
genetically modified mesenchymal stem cells includes, without
limitation, the following amounts and ranges of amounts: (i)
from about lxl05 to about lxl09 cells/kg body weight [sic]; (ii)
from about lx 106 to about lx 108 cells/kg body weight [sic] ...
(vii) about lxl05 cells/kg body weight [sic]; (viii) about lxl06
cells/kg body weight [sic]; (ix) about 5xl06 cells/kg body weight
[sic]; ....
Id. at col 10, 11. 48---63. Claims 14 and 15 ofNelson recite, respectively:
4 We note that Dr. Li states that: "the additional data, submitted as Exhibit B
in our Response filed on February 28, 2013, demonstrate beneficial
treatment of nude mice at approximately 2.5 x 104 cells per mouse for each
treatment cycle." Li Deel. ,r 8. We are unable to discern any express
disclosure of such a dosage, but we observe that this dosage, for a mouse
with a body mass of between 20 and 25 grams (see Li Deel. Ex. B) appears
to correspond to a dosage of approximately 1.0 x 106 MSCs/kg body mass.
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and
14. The method of claim 1, wherein the therapeutically
effective number of genetically modified mesenchymal stem
cells is from about 1x105 to about 1x109 cells/kg body weight
[sic]
15. The method of claim 1, wherein the therapeutically
effective number of genetically modified mesenchymal stem
cells is from about lx 106 to about lx 108 cells/kg body weight
[sic].
Nelson thus teaches dosages that substantially overlap those presented by
Appellants in their Specification and as presented in Appendix B of the Li
Declaration. See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) ("In
cases involving overlapping ranges, we and our predecessor court have
consistently held that even a slight overlap in range establishes a prima facie
case of obviousness").
Nor do we discern any express language, or suggestion, in Nelson to
indicate, as Appellants argue, that these dosages, and ranges of dosages, as
being somehow "aspirational." Rather, we agree with the Examiner that a
person of ordinary skill in the art would have recognized, upon
comprehending the teachings and suggestions of Nelson, that Nelson teaches
that dosages of 1 x 105 to 1 x 106 MSCs/ kg body mass are therapeutically
effective. See Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807
(Fed. Cir. 1989) (holding that, in the context of an obviousness analysis, "all
disclosures of the prior art, including unpreferred embodiments, must be
considered"). We therefore are not persuaded by Appellants' argument.
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Issue 2
Appellants argue that the Examiner erred in finding that Appellants'
allegedly unexpected results are not commensurate in scope with the
claimed invention. App. Br. 7.
Analysis
Appellants argue that the unexpected property of achieving
therapeutic effectiveness at the low dosage of 1 x 106 cells/kg body mass is
an inherent property of the claimed human MSCs. App. Br. 8. According to
Appellants, this inherent property remains a characteristic of the claimed
MS Cs regardless of the cell number or concentration or dosage form. Id.
Therefore, contend Appellants, the scope of the invention of claim 8 is
commensurate with the surprising and unexpected results, and claim 8 is
non-obvious, and thus patentable, over the prior art references cited by the
Examiner. Id. Furthermore, Appellants assert, since the remaining claims
each incorporate all of the limitations recited in claim 8, they are also
patentable over the cited references. Id.
Appellants note further that the Examiner also finds that the claims
are not commensurate in scope with the surprising results because the dose
itself is not recited in the claims. App. Br. 8.
Appellants first point out that our reviewing court's decision in
Genetics Institute, LLC v. Novartis Vaccines & Diagnostics, Inc.,
655 F.3d 1291 (Fed. Cir. 2011) establishes that "absolute identity of scope"
between a claimed invention and the unexpected results is "not required" for
patentability. App. Br. 8 (citing Genetics, 655 F.3d at 1308). Appellants
assert that the Federal Circuit's decision in Genetics explains that claims
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reciting 90% sequence identity to an amino acid sequence encoded by a
deposited plasmid are patentable despite the fact that some members of the
recited genus do not possess the unexpected property of stability, a property
required to support the patentability of the claim. Id.
Appellants also argue that the Examiner's suggestion of amending the
claims is an implicit admission that the unexpected results are sufficient to
overcome the Examiner's primafacie case of obviousness. App. Br. 8.
Furthermore, Appellants assert that the very issue of whether a claim must
explicitly recite an unexpected yet inherent property that supports
patentability has been addressed and rejected by the Federal Circuit in
Genetics. According to Appellants, the claims at issue in Genetics recited
the composition and did not recite any of the unexpected, particular stability
characteristics of the composition. Id. at 9 (citing Genetics, 655 F.3d at
1307). Similarly, Appellants argue, the inherently unexpected properties of
Appellants' claimed human fetal MS Cs are sufficient to overcome the prima
facie case of obviousness even if the claims contain no explicit recitation of
such surprising properties. Id.
We are not persuaded by Appellants' argument. We agree with
Appellants that the structure of a claimed compound and its properties are
inseparable for purposes of§ 103, and that that every property of a claimed
compound need not be fully recognized as of the filing date of the patent
application to be relevant to nonobviousness. See Sanofi-Synthelabo v.
Apotex, Inc., 550 F.3d 1075, 1086 (Fed. Cir. 2008); Knoll Pharm. Co. v.
Teva Pharms. USA, Inc., 367 F.3d 1381, 1385 (Fed. Cir. 2004).
Nevertheless, as we have explained supra, we are not persuaded that
Appellants' claimed compositions exhibit, or inherently possess, properties
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that would have been unexpected to a person of ordinary skill in the art
conversant with the combined prior art references cited by the Examiner. It
is for this reason, first and foremost, that the present facts are distinguishable
from those of Genetics.
Appellants do not contest the Examiner's findings and conclusion that
the combined cited prior art teach all of the limitations of their claimed
composition. Rather, Appellants argue that their prima facie obvious
composition has hitherto unknown and unexpected properties. In such an
instance, the burden shifts to Appellants to demonstrate that the unexpected
properties of the composition were not inherently present in the composition
as taught by the prior art. As the predecessor of our reviewing court has
held:
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
... Whether the rejection is based on 'inherency' under 35 U.S.C.
§ 102, on 'prima facie obviousness' under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its
fairness is evidenced by the PTO' s inability to manufacture
products or to obtain and compare prior art products.
In re Best, 562 F.2d 1252, 1255 (C.C.P.A. 1977). Appellants have adduced
no persuasive evidence that the prior art compositions did not inherently
possess the allegedly unexpected properties that they now argue are
unexpected in the claimed composition. Indeed, as we explained supra, the
Examiner's cited prior art teaches that the compositions of the prior art do
possess those same qualities that Appellants argue.
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We consequently affirm the Examiner's rejection of claims 8, 10, and
12-23.
DECISION
The Examiner's rejection of claims 8, 10, and 12-23 under 35 U.S.C.
§ 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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