Ex Parte Delfani et al

Patent Trial and Appeal Board

Aug 21, 2018

13159623 (P.T.A.B. Aug. 21, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/159,623 06/14/2011
58249 7590 08/23/2018
COOLEYLLP
ATTN: IP Docketing Department
1299 Pennsylvania Avenue, NW
Suite 700
Washington, DC 20004
FIRST NAMED INVENTOR
Kioumars Delfani
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.
NER0-004D01US
322086-2013
CONFIRMATION NO.
1821
EXAMINER
WANG, CHANG YU
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
08/23/2018 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):
zIPPatentDocketingMailbox US @cooley.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KIOUMARS DELP ANI, ANN MARIE JANSON,
H. GEORG KUHN, KARLHEINZ PLATE, ANNE SCHANZER,
FRANK-PETER WACHS, and MING ZHAO
Appeal2017-001033
Application 13/159,623 1
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREY N. FRED MAN, and
DAVID COTTA, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a method of
alleviating a symptom of a disease or disorder of the neural system. The
Examiner rejected the claims for obviousness and indefiniteness.
We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
1 Appellants state that the "real party in interest is Newron Sweden AB, the
assignee of the application from all inventors." Appeal Br. 2.
Appeal2017-001033
Application 13/159,623
STATEMENT OF THE CASE
The following rejections are before us for review:
(1) Claims 1, 6-8, and 11-14, under 35 U.S.C. § I03(a) as being
obvious over Hu,2 Gao, 3 Hayward,4 Weiss, 5 Knight,6 and Maysinger7 (Final
Act. 3-16; Ans. 2-6); and
(2) Claim 13, under 35 U.S.C. § 112, second paragraph, for
indefiniteness (Final Act. 16).
Claim 1 is representative and reads as follows:
1. A method of alleviating a symptom of a disease or
disorder of the nervous system in a patient in need thereof
comprising administering VEGF [ vascular endothelial growth
factor] to a neural tissue of said patient in a therapeutically
effective amount sufficient to induce the proliferation or
differentiation of, or modulate the survival of, a neural stem cell
or neural progenitor cell located in said neural tissue, wherein
the VEGF is VEGF-A16s (SEQ ID N0:32) and the VEGF-A16s
is administered in an amount of 0.5 ng/kg/day to 500 ng/kg/day.
Appeal Br. 26.
INDEFINITENESS
In rejecting claim 13 as indefinite, the Examiner determined that the
term "VEGF agonist" lacks antecedent basis. Final Act. 16.
2 US 6,040,157 (issued Mar. 21, 2000).
3 US 2002/0177193 Al (published Nov. 28, 2002).
4 WO 96/27007 Al (published Sept. 6, 1996).
5 US 6,294,346 Bl (issued Sept. 25, 2001).
6 Elaine V. Knight et al., A Review of Nonclinical Toxicology Studies of
Becaplermin (rhPDGF-BB), 176 Am. J. Surgery (Suppl. 2A) 55S---60S
(1998).
7 Dusica Maysinger and Anne Morinville, Drug delivery to the nervous
system, 15 Trends Biotechnol. 410-418 (1997).
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Application 13/159,623
Appellants do not assert error in the Examiner's determination.
Rather, Appellants state that they "are not requesting review of this instant
rejection. Upon conclusion of Appeal proceedings, Applicants will amend
claim 13 to delete 'VEGF agonist' to render the rejection moot." Appeal Br.
20.
Because Appellants do not contest in the Examiner's indefiniteness
rejection, we summarily affirm it. See MPEP § 1205.02 (Board may
summarily sustain grounds of rejection for which no substantive argument
was presented).
OBVIOUSNESS
The Examiner's Prima Facie Case
In rejecting representative claim 1 over Hu, Gao, Hayward, Weiss,
Knight, and Maysinger, the Examiner cited Hu, Gao, and Hayward as
evidence suggesting the administration of the claimed growth factor,
VEGF-A165, to neural tissue in a patient, as claim 1 requires. See Ans. 4---6,
8-9.
In particular, the Examiner reasoned, an ordinary artisan would have
been motivated to administer VEGF-A16s to a patient's neural tissue "with
an expectation of success because in vivo administration [ of] VEGF protein
or DNA including VEGF-A165 can enhance neurogenesis and improve the
neuronal loss in neurodegenerative diseases including Parkinson's disease,
and VEGF-A165 (SEQ ID N0:32) has been shown to have activities of
promoting neural survival and proliferation." Id. at 9.
The Examiner cited Weiss and Knight as evidence that administration
routes recited in some of the dependent claims (see Appeal Br. 26 ( claims 6
and 7)) were known routes of administration for growth factors, including
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for treatment of neural disorders. Ans. 6-7. The Examiner cited Maysinger
as evidence that delivery vehicles recited in certain dependent claims (see
Appeal Br. 27 (claims 11-13)) were known in the art for delivering
therapeutic agents to the central nervous system (CNS). Ans. 7-8.
As to representative claim 1 's VEGF-A16s dosage rate range of 0.5
ng/kg/day to 500 ng/kg/day, the Examiner found that the claimed range
overlapped the dosage rate ranges taught in Hu, Gao, and Knight, and
therefore would have been obvious. Id. at 10-11.
As to claim 1 's dosage rate range, the Examiner additionally reasoned
that, in view of the cited references' teachings, an ordinary artisan would
have been motivated to determine the optimal dosage rate of VEGF-A165,
and that, absent a showing of criticality, the claimed dosage rate range
would have been obvious. Id. at 11 ( citing In re Aller, 220 F .2d 454, 456
(CCP A 1955) ("[W]here the general conditions of a claim are disclosed in
the prior art, it is not inventive to discover the optimum or workable ranges
by routine experimentation."); also citing In re Woodruff, 919 F.2d 1575,
1578 (Fed. Cir. 1990) (In cases where "the difference between the claimed
invention and the prior art is some range or other variable within the claims .
. . , the applicant must show that the particular range is critical, generally by
showing that the claimed range achieves unexpected results relative to the
prior art range.")).
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
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record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the present appeal, having carefully considered the arguments and
evidence advanced by Appellants and the Examiner, Appellants do not
persuade us that the preponderance of the evidence fails to support the
Examiner's conclusion of obviousness as to claim 1. In particular, we
acknowledge, as Appellants contend (see Appeal Br. 5-24; Reply Br. 3-14),
that the cited references, in large part, are directed to administration of
molecules other than claim 1 's VEGF-A165. Appellants' arguments,
however, fail to take into account teachings in the cited references,
particularly in Hayward, suggesting the administration of VEGF-A165 to a
patient's neural tissue, as claim 1 requires.
We first note that, although claim 1 recites "VEGF-A16s (SEQ ID
N0:32)" as the administered polypeptide (Appeal Br. 26 (claim 1)), the
portion of the Specification cited by Appellants as support for the
administered polypeptide (see id. at 2) also uses the term "VEGF-165" to
refer to the administered polypeptide. See Spec. ,r 104. s,9
Turning to the prior art, Hayward uses the polypeptide recited in
Appellants' claim 1 as a reference point for the polypeptides Hayward
describes as its invention:
8 In citing to their Specification, Appellants cite to the published application,
US 2012/0077741 Al (published Mar. 29, 2012). We do the same for
convenience and consistency.
9 Although ,r 104 of the published Specification cites to SEQ ID NO: 3 for
the amino acid sequence ofVEGF-165 (see Spec. ,r 104), SEQ ID NO: 3 of
the sequence disclosure portion of the published Specification does not
appear to be an amino acid sequence. See id. at pp. 35-36.
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The amino acid sequence set forth in SEQ ID N0:2
corresponds to human VEGF (referred to herein as "VEGF 16s").
Accordingly, the molecule of the present invention is VEGF-
like or is a homologue of VEGF but comprises an amino acid
sequence which is similar but non-identical to the amino
sequence of VEGF ....
Preferably, the percentage similarity is at least about 30%, more
preferably at least about 40%, still more preferably at least
about 50%, still even more preferably at least about 60-70%,
yet even more preferably at least about 80--95% to all or part
of the amino acid sequence set forth in SEQ ID N0:2.
Hayward 4: 11-28 ( emphasis added); compare also SEQ ID NO: 2 of
Hayward (Hayward 38-39) to Appellants' SEQ ID NO: 32 (Spec. pp. 44--
45) (amino acid sequences are identical).
We acknowledge that the "SOMl 75" polypeptide described by
Hayward as part of its invention (see Hayward 7:3) has only about 33%
homology with VEGF-A165 at the protein level (see id. at Fig. 6 (iii)).
As seen above, however, Hayward contemplates its invention as
encompassing the use of polypeptides with at least about 80-95% similarity
to the VEGF-A165 polypeptide recited in Appellants' claim 1. See id. at
4:25-28.
Hayward, moreover, discloses that polypeptides having as much as
95% similarity to the VEGF-A165 polypeptide recited in Appellants' claim 1,
and having properties in common with the polypeptide of Appellants' claim
1, may be administered to promote neural survival and proliferation in a
patient:
A further aspect of the present invention provides a method of
promoting neural survival and/or proliferation in a mammal,
said method comprising administering to said mammal an
effective amount of a recombinant proteinaceous molecule
having the characteristics:
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Application 13/159,623
(i) comprises an amino acid sequence having at least
about 15% similarity but at least about 5% dissimilarity to the
sequence set forth in SEQ ID N0:2;
(ii) exhibits at least one property in common with
vascular endothelial growth factor (VEGF),
said administration being for a time and under conditions
sufficient to induce astroglial proliferation.
Id. at 8:25-9:2 ( emphasis added).
Hayward discloses, in addition, that the VEGF-A16s polypeptide
recited in Appellants' claim 1 can be co-administered with the polypeptides
of Hayward's invention. Id. at 7:28-30 ("The VEGF-like molecule of the
present invention will be useful in the development of a range of therapeutic
and/or diagnostic applications alone or in combination with other
molecules such as VEGF.") (emphasis added).
Hayward also discloses experimental results indicating that the
VEGF-A16s polypeptide recited in Appellants' claim 1 promotes neuronal
survival in an animal model. Id. at 29 (Example 7) ("The effects of VEGF
and SOMl 75 proteins on embryonic day 8 chick sensory neurons were
determined using the method ofNurcombe et al (1992) .... The results
show that VEGF is effective in promoting neuronal survival but that this
requires the presence of glial cells."); see also id. at Figs. 16, 17 (graphic
presentation of results of Example 7).
Thus, on the current record, as seen above, Hayward discloses (a)
experimental results indicating that the VEGF-A16s polypeptide recited in
Appellants' claim 1 promotes neuronal survival in an animal model, (b) that
polypeptides having as much as 95% similarity to the VEGF-A165
polypeptide recited in Appellants' claim 1, and having properties in common
with the polypeptide of Appellants' claim 1, may be administered to
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Application 13/159,623
promote neural survival and proliferation in a patient, and ( c) that the
VEGF-A165 polypeptide recited in Appellants' claim 1 can be co-
administered with the polypeptides of Hayward's invention. Given these
teachings, we agree with the Examiner that an ordinary artisan had a good
reason for, and a reasonable expectation of success in, administering the
VEGF-A16s polypeptide recited in Appellants' claim 1 to promote neuronal
survival and proliferation in a patient.
Turning to the other references, we acknowledge, as Appellants
contend, that the focus of Hu is the therapeutic use of the polypeptide
VEGF2 (see, e.g., Hu, abstract), which has only about 30% amino acid
identity with VEGF (see id. at Fig. 4). As discussed above, however,
Hayward teaches that the VEGF-A165 polypeptide recited in Appellants'
claim 1 promotes neural survival, and that polypeptides having 95% identity
with VEGF-A165 were similarly useful, including in combination with
VEGF-A165. Appellants do not persuade us, therefore, that the Examiner
erred in finding that an ordinary artisan had a good reason for, and a
reasonable expectation of success in, administering the VEGF-A 165
polypeptide recited in Appellants' claim 1 to promote neuronal survival
and/or proliferation in a patient.
We acknowledge, as Appellants contend, that Gao' s focus is on the
growth factor polypeptide "zvegf3" (Gao ,r 57), and its therapeutic uses,
which include administration for treating neurodegenerative disorders like
Alzheimer's and Parkinson's diseases (see id. ,r 155).
Gao, however, also discloses that zvegf3 "polypeptides can be
administered alone or in combination with other vasculogenic or angiogenic
agents, including VEGF." Id. ,r 153. Accordingly, although Gao's central
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focus might not be on the VEGF-A165 polypeptide recited in Appellants'
claim 1, or closely similar compounds, Gao' s disclosure of the co-
administration of VEGF with its inventive zvegf3 polypeptides bolsters the
Examiner's findings that an ordinary artisan had a good reason for, and a
reasonable expectation of success in, administering the VEGF-A165
polypeptide recited in Appellants' claim 1 to promote neuronal survival
and/or proliferation in a patient.
In sum, for the reasons discussed, Appellants do not persuade us that
the Examiner erred in finding that an ordinary artisan had a good reason for,
and a reasonable expectation of success in, administering the VEGF-A165
polypeptide recited in Appellants' claim 1 to promote neuronal survival
and/or proliferation in a patient.
Appellants also do not persuade us that the Examiner erred in finding
that, given the prior art's suggestion to administer the VEGF-A165
polypeptide to promote neuronal survival and/or proliferation, an ordinary
artisan would have considered it a routine matter to determine suitable
dosages for that purpose. Specifically, as the Examiner noted, it is well
settled that "where the general conditions of a claim are disclosed in the
prior art, it is not inventive to discover the optimum or workable ranges by
routine experimentation." In re Aller, 220 F.2d at 456.
As the Examiner also noted, in cases where "the difference between
the claimed invention and the prior art is some range or other variable within
the claims ... , the applicant must show that the particular range is critical,
generally by showing that the claimed range achieves unexpected results
relative to the prior art range." In re Woodruff, 919 F .2d at 1578.
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In the present case, a number of disclosures in the references cited by
the Examiner support the Examiner's finding (Ans. 11) that the dosage of
therapeutic growth factors was a result-effective variable routinely
determined by ordinary artisans. See Hu at 40:36-39 (disclosing in relation
to the administration of DNA or RNA encoding VEGF2 that the
"appropriate and effective dosage of nucleic acid sequence can readily be
determined by those of ordinary skill in the art and may depend on the
condition being treated and the route of administration"); see also Gao ,r 156
(disclosing in relation to zvegf3 that "the exact dose [is] determined by the
clinician according to accepted standards, taking into account the nature and
severity of the condition to be treated, patient traits, etc." and that
"[ d]etermination of dose is within the level of ordinary skill in the art"); see
also Knight 55S (disclosing administration of different doses of recombinant
human platelet-derived growth factor-BB in mice, rats, and monkeys to
determine non-toxic dosages).
We acknowledge, as Appellants contend, that these teachings relate to
growth factor polypeptides other than the VEGF-A165 polypeptide recited in
Appellants' claim 1. Nonetheless, viewing the cited references as a whole,
we discern no error in the Examiner's determination that the dosage of a
growth factor administered to treat a disorder of the nervous system was a
result-effective variable routinely optimized by ordinary artisans.
Accordingly, we also discern no error in the Examiner's determination
that an ordinary artisan, prompted by the teachings in the cited references to
administer VEGF-A16s to treat a nervous system disease or disorder, would
have considered it a routine matter to determine suitable dosages VEGF-
A16s. Because Appellants have identified no specific unexpected results
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coming from administration of VEGF-A165 at the dosage range recited in
representative claim 1, and therefore have not shown the claimed dosage
range to be critical, we agree with the Examiner that, based on the current
record, the VEGF-A165 dosage range recited in Appellants' claim 1 would
have been an obvious feature of the process suggested by the references.
In sum, for the reasons discussed, Appellants do not persuade us that
the Examiner erred in finding that an ordinary artisan had a good reason for,
and a reasonable expectation of success in, administering the VEGF-A165
polypeptide recited in Appellants' claim 1 to promote neuronal survival
and/or proliferation in a patient with a disease or disorder of the nervous
system. As also discussed above, Appellants do not persuade us that the
Examiner erred in finding that, given the prior art's suggestion to administer
the VEGF-A16spolypeptide to promote neuronal survival and/or
proliferation, an ordinary artisan would have considered it an obvious matter
of routine optimization to determine suitable dosages for that purpose.
Because Appellants do not persuade us, therefore, that the Examiner
erred in finding that the prior art would have suggested administering the
active agent recited in claim 1, to the claimed patient, at the claimed dosage,
we affirm the Examiner's rejection of claim 1, over the cited references.
Because they were not argued separately, claims 6-8, and 11-14 fall with
claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 1, 6-8, and 11-14, under 35 U.S.C. § 103(a) as being obvious over
Hu, Gao, Hayward, Weiss, Knight, and Maysinger.
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For the reasons discussed, we also affirm the Examiner's rejection of
claim 13, under 35 U.S.C. § 112, second paragraph, for indefiniteness.
TIME PERIOD
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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