Ex Parte Pan et al

Patent Trial and Appeal Board

Apr 27, 2016

12540703 (P.T.A.B. Apr. 27, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/540,703 08/13/2009
21839 7590 04/29/2016
BUCHANAN, INGERSOLL & ROONEY PC
POST OFFICE BOX 1404
ALEXANDRIA, VA 22313-1404
FIRST NAMED INVENTOR
ClarkQ. Pan
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.
0081563-000022 1860
EXAMINER
KIM, ALEXANDER D
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
04/29/2016 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):
ADIPDOC 1@BIPC.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CLARK Q. PAN, JOHN E. MURPHY,
BAISONG MEI, JONATHAN S. STRAUSS,
HENDRI TJANDRA, JIANMIN CHEN, THOMAS BARNETT,
LIANG TANG, and DEQIAN WANG
Appeal2013-009173
Application 12/540,703
Technology Center 1600
Before JEFFREY FREDMAN, RICHARD J. SMITH, and
KIMBERLY McGRAW, Administrative Patent Judges.
McGRAW, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant appeals from the Examiner's final
rejections of 58 and 60-67. App. Br. 2. Claims 1-57 and 59 are cancelled. Id.
We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
Appeal2013-009173
Application 12/540,703
STATEMENT OF THE CASE
The present invention relates to factor VIII polypeptides covalently attached
to biocompatible polymers. Claims 58 and 67 are independent. Claim 58 is
representative of the subject matter appeal and is reproduced below.
58. An isolated polypeptide conjugate comprising a functional factor
VIII polypeptide and one or more biocompatible polymers, wherein the
functional factor VIII polypeptide comprises the amino acid sequence
of SEQ ID NO: 4 or an allelic variant thereof and has a B-domain, and
further wherein the biocompatible polymer comprises polyalkylene
oxide and is covalently attached to the functional factor VIII
polypeptide at the B-domain.
App. Br. 16. (Claims App'x).
REJECTIONS ON APPEAL
Claims 58 and 60-67 stand rejected under 35 U.S.C. §§ 102(a) and (e) as
anticipated by Bossard et al., (US 2004/0235734 Al, published Nov. 25, 2004
"Bossard"). Ans. 4--10; Final Act. 9-12.
Claims 58 and 60-67 stand rejected under 35 U.S.C. § 102(a) as anticipated
by Rostin et al., B-Domain Deleted Recombinant Coagulation Factor VIII
Modified with Monomethoxy Polyethylene Glycol, 11 Bioconjugate Chem, 387-96
(2000) ("Rostin"). Ans. 10-13; Final Act. 12-15.
ANALYSIS
Bossard
The Examiner finds Bossard teaches covalently attaching biocompatible
polymer mPEG-maleimide to factor VIII polypeptides by reacting the maleimide
activated PEG with the thiol of cysteine residues within factor VIII. Ans. 5 (citing
Bossard i-f 122); see also Final Act. 11 (citing Bossard i1i170, 113, 114). The
Examiner states that although Bossard does not explicitly teach that the mPEG-
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Application 12/540,703
maleimide is covalently attached to the B-domain of factor Vlll, as required by the
independent claims, attachment within the B-domain is an inherent feature of
reaction as evidenced by Appellants' Specification. Ans. 5---6 (citing Spec. i-fi-f 151-
152). Specifically, the Examiner finds that because the conjugation reaction
described in Appellants' Specification is identical to the conjugation reaction
disclosed by Bossard, it is inherent that the B-domain of factor VIII will covalently
bind to the mPEG-maleimide. Id. at 6.
Appellants argue the conjugation reaction used by Appellants is not identical
to the reaction used in Bossard, and therefore Examiner erred in finding Bossard
inherently discloses a biocompatible polymer that is covalently attached to a
functional factor VIII polypeptide at the B-domain, as required by the claims.
We agree with Appellants. The Examiner bears the initial burden of
presenting aprimafacie case ofunpatentability. In re Oetiker, 977 F.2d 1443,
1445 (Fed. Cir. 1992). Anticipation requires that each and every limitation be
disclosed in the prior art reference, either expressly or inherently. In relying upon
the theory of inherency, "the examiner must provide a basis in fact and/or technical
reasoning to reasonably support the determination that the allegedly inherent
characteristic necessarily flows from the teachings of the applied prior art." Ex
parte Levy, 17 USPQ2d 1461, 1464 (BPAI 1990)(emphasis in original). In
general, a limitation is inherent if it is the "natural result flowing from" the explicit
disclosure of the prior art. Schering Corp. v. Geneva Pharms., 339 F.3d 1373,
1379 (Fed. Cir. 2003). Where the structure taught by the prior art is produced by
identical or substantially identical processes used by the applicant, the claimed
properties or function are presumed to be inherent and the burden shifts to the
applicant to rebut the presumption. See e.g., In re Best, 562 F.2d 1252, 1254-55
(CCP A 1977). However, before applicant can be put to this burdensome task, the
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Application 12/540,703
Examiner must provide enough evidence or scientific reasoning to establish that
the Examiner's belief that the property is inherent is a reasonable belief. See e.g.,
Ex parte Levy, 17 USPQ2d 1461, 1464---65 (BPAI 1990); Ex parte Skinner, 2
USPQ2d 1788, 1789 (BP AI 1986).
Here, the Examiner has not shown that identical processes are used by
Bossard and Appellants to conjugate factor VIII with mPEG-maleimide.
Appellants' process requires first reducing the factor VIII with reducing agent
tris(2-carboxyethyl)phosphine ("TCEP"), followed by TCEP removal and
treatment with excess amounts of PEG-maleimide. Spec. i-fi-f 148, 151. In contrast,
Bossard does not disclose use of a reducing agent or that excess PEG is utilized.
Appellants' Specification states that reduction and denaturation of factor VIII and
use of over 100-fold excess PEG is required to pegylate factor VIII and pegylation
cannot occur in significant amount unless under such conditions. Spec. i-f 143
(stating that absent such conditions the factor VIII will not pegylate because the
cysteines either form disulfide bonds or remain buried within factor VIII).
Other than stating Bossard uses the identical processes, a finding with which
we do not agree, the Examiner does not provide any other evidence or argument
that Bossard discloses, either expressly or inherently, a biocompatible polymer that
is covalently attached to the functional factor VIII polypeptide at the B-domain.
The mere fact a certain thing may result from a given set of circumstances is not
sufficient to establish inherent anticipation. In re Robertson, 169 F.3d 743, 745
(Fed. Cir. 1999). As such, on this record, the Examiner has not provided sound
basis for believing the products of Appellants and the prior art are the same; nor
has the Examiner provided sufficient evidence that Bossard expressly or inherently
describes a biocompatible polymer covalently attached to functional factor VIII
polypeptide at the B-domain, as required by independent claims 58 and 67.
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Application 12/540,703
Accordingly, we reverse the Examiner's stated anticipation rejection of
independent claims 58 and 67 and the claims which depend therefrom.
Ros tin
Rostin, titled "B-Domain deleted Recombinant Coagulation Factor VIII
Modified with Monomethoxy Polyethylene Glycol" is directed to pegylation of a
recombinant factor VIII having a deletion within the B-domain wherein the Ser
743 of the heavy chain C-terminal was fused to the Gln 1638 of the light chain B-
terminal (r-FVIII SQ). The Examiner finds that because r-FVIII SQ retains a 14
amino acid segment from the B-domain, r-VIII SQ is an allelic variant of a factor
VIII polypeptide and has a B-domain.
The Examiner states that although Rostin does not expressly teach
covalently attaching a biocompatible polymer to the functional factor VIII
polypeptide at the B-domain, one of the 14 amino acids within the shortened B-
domain is a lysine (Lysine 1644), and it is inherent that the mPEG covalently
attaches to this Lysine 1644. Ans. 12.
We disagree. As noted above, the initial burden of establishing
a prima facie basis to deny patentability to a claimed invention rests upon the
examiner. Oetiker, 977 F.2d at 1445. The Examiner must provide a basis in fact
and/or technical reasoning to reasonably support the determination that the
allegedly inherent characteristics necessarily flow from the teachings of the applied
prior art. Levy, 17 USPQ2d at 1464. Inherency may not be established by
probabilities or possibilities. The mere fact that a certain thing may result from a
given set of circumstances is not sufficient. Oelrich, 666 F.2d 578, 581 (CCPA
1981 ).
As noted by Appellants, Table 2 of Rostin shows that the degree of
modification ranges between only 0.8 to 9.5 moles of PEG per each mole of r-
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FY Ill SQ. Given the large number of lysines1 available for conjugating in r-FVlll
SQ, and the low degree of modification, the Examiner's reasoning does not
reasonably support the determination that the mPEG of Rostin necessarily attaches
to the single lysine located in the B-domain. As such, the Examiner has not
established a prima facie of case anticipation and we do not sustain the Examiner's
rejection of independent claims 58 and 67 as anticipated by Rostin, or the claims
that depend therefrom.
Additionally, we disagree with the Examiner's finding that r-VIII SQ is an
allelic variant of a factor VIII polypeptide. "Even when guidance is not provided
in explicit definitional format, 'the specification may define claim terms by
implication such that the meaning may be found in or ascertained by a reading of
the patent documents."' Irdeto Access, Inc. v. Echostar Satellite Corp., 383 F.3d
1295, 1300 (Fed. Cir. 2004) (internal single quotation marks and citations omitted.)
Appellants have defined allelic variant as naturally occurring. See e.g., Spec. i-f 67
(stating Factor VIII has multiple degradation or processed forms in the natural state
and that allelic variations likely exist); see also May 21, 2012 Response to Office
Act. at 6-8 (describing the prior art publications discussing allelic variants of
human factor VIII); App. Br. 12; Reply Br. 9-10. As such, we agree with
Appellants that one skilled in the art, reading Appellants' Specification, would
understand allelic variants are naturally occurring alternative forms/variants
encoded by a gene on a chromosome. As r-VIII SQ is man-made and was never
encoded by a gene on a chromosome, r-VIII SQ is not an allelic variant of a
functional factor VIII polypeptide as required by the independent claims. For this
1 A review of SEQ ID NO: 4 shows that the polypeptide (excluding amino
acids 743 through 1638) contains over 75 lysines.
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additional reason, we do not sustain the Examiner's rejection of independent
claims 58 and 67 and the claims that depend therefrom.
DECISION
The Examiner's rejections of the appealed claims are reversed.
REVERSED
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