Ex Parte Carmeliet et al

Patent Trial and Appeal Board

Mar 24, 2017

13785253 (P.T.A.B. Mar. 24, 2017)

United States Patent and Trademark Office
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/785,253 03/05/2013 Peter CARMELIET BJS-5117-34 2450
23117 7590 03/28/2017
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON, VA 22203
EXAMINER
GAMBEL, PHILLIP
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
03/28/2017 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):
PTOMAIL@nixonvan.com
pair_nixon @ firsttofile. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PETER CARMELIET, DESIRE COLLEN,
SANDRO De FALCO, and RUVO MENOTTI1
Appeal 2016-000702
Application 13/785,253
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
1 Appellants state the real parties-in-interest are Life Sciences Research
Partners VZW and Vlaams Interuniversitair Instituut Voor Biotechnologie
Vzw. App. Br. 3.
Appeal 2016-000702
Application 13/785,253
DECISION ON APPEAL
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 2, 4, 5, 7, and 9. Specifically,
claims 1, 2, 4, and 5 stand rejected as unpatentable under 35 U.S.C. § 102(b)
as being anticipated by M.J. Bottomley et al., Placenta growth factor (PIGF)
induces vascular endothelial growth factor (VEGF) secretion from
mononuclear cells and is co-expressed with VEGF in synovial fluid, 119
Clin. Exp. Immunol. 182-88 (2000) (“Bottomley”).
Claims 1, 2, 4, 5, 7, and 9 stand rejected as unpatentable under
35 U.S.C. § 103(a) as being obvious over the combination of Bottomley,
Shitara et al. (US 6,986,890 Bl, January 17, 2006) (“Shitara”), Boulton et al.
(WO 99/24056, May 20, 1999) (“Boulton”), and Ferrara et al. (US 6,455,283
Bl, September 24, 2002) (“Ferrara”).2,3
2 The Examiner also made the following rejections under the doctrine of
nonstatutory obviousness-type double patenting: (1) claims 1, 2, 4, 5, 7, and
9 over claim 1 of U.S. Patent No. 7,357,929; (2) claims 1, 2, 4, 5, 7, and 9
over claims 1—9 of U.S. Patent No. 7,482,004; (3) claims 1, 2, 4, 5, 7, and 9
over claims 1—7 of U.S. Patent No. 7,867,490; and (4) claims 1, 2, 4, 5, 7,
and 9 over claims 1—6 of U.S. Patent No. 8,758,748. App. Br. 8. These
rejections have been withdrawn by the Examiner. Ans. 3.
3 Appellants assert:
The following statements, objection and provisional
rejections of the Office Action dated October 29, 2014, are not
presented for review as not being appealable:
• The objection to claim 7 and withdrawn claims 8 and 10 stated
on page 3 of the Office Action dated October 29, 2014;
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Application 13/785,253
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
• The provisional obviousness-type double patenting rejection of
claims 1, 2, 5, 7 and 9 over claims 1—17 of copending U.S.
Application No. 13/785,559 stated on page 9 of the Office Action
dated October 29, 2014;
• The provisional obviousness-type double patenting rejection of
claims 1, 2, 5, 7 and 9 over claims 10-10 of copending U.S.
Application No. 13/785,643 stated on page 9 of the Office Action
dated October 29, 2014;
• The provisional obviousness-type double patenting rejection of
claims 1, 2, 5, 7 and 9 over claims 8—16 of copending U.S.
Application No. 14/170,997 stated on page 9 of the Office Action
dated October 29, 2014;
• The statement - without a statutory basis for a rejection - on
page 9 of the Office Action dated October 29, 2014 that “Claims
1, 2, 4, 5, 7 and 9 are directed to an invention not patentable
distinct from claim 1 of commonly assigned U.S. Patent No.
7,357,929 (1449)... for the reasons above”;
• The statement - without a statutory basis for a rejection - on
page 9 of the Office Action dated October 29, 2014 that “Claims
1, 2, 4, 5, 7 and 9 are directed to an invention not patentable
distinct from ... claims 1—7 of commonly assigned U.S. Patent
No. 7,867,490 (1449)... for the reasons above”; and
• The statement - without a statutory basis for a rejection - on
page 9 of the Office Action dated October 29, 2014 that “Claims
1, 2, 4, 5, 7 and 9 are directed to an invention not patentable
distinct from ... claims 1—6 of commonly assigned U.S. Patent
No. 8,758,748 (1449)... for the reasons above.”
App. Br. 7 n.6. Because Appellants explicitly do not contest the above-
noted rejections on appeal, we summarily affirm the rejections.
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Application 13/785,253
NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to molecules that can inhibit the
binding of placental growth factor (“P1GF”) to its receptor (“VEGFR-1”),
such as monoclonal antibodies and tetrameric peptides, and to the use of
these molecules to treat pathological processes. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of suppressing inflammation in a mammal
by administering to a mammal in need of suppressing
inflammation an antibody or a fragment thereof that specifically
binds to placental growth factor and that neutralizes the activity
of placental growth factor, such that said inflammation is
suppressed.
App. Br. 24.
ISSUES AND ANALYSES
We agree with, and adopt, the Examiner’s findings and conclusion
that the appealed claims are anticipated by, and obvious over, the combined
cited prior art under 35 U.S.C. §§ 102(b) and 103(a). We address the
arguments raised by Appellants below.
A. Rejection of claims E 2, 4, and 5 under 35 U.S.C. $ 102(b)
Issue
Appellants argue the Examiner erred in finding Bottomley discloses a
method of suppressing inflammation by administering to a mammal in need
an antibody or a fragment thereof that specifically binds to placental growth
factor. App. Br. 8.
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Application 13/785,253
Analysis
Appellants argue the Examiner incorrectly relies upon the teachings of
Bottomley as disclosing the disputed limitation. App. Br. 9. Appellants
assert Bottomley discloses: “Placental growth factor (P1GF) induces
vascular endothelial growth factor (VEGF) secretion from mononuclear cells
and is co-expressed with VEGF synovial fluid,” and that a “combination of a
monoclonal and a biotinylated polyclonal antibody specific for P1GF” were
used to measure “SF [synovial fluid] and plasma P1GF levels ... by an in-
house EFISA.” Id. (quoting Bottomley 183). However, Appellants argue,
Bottomley does not disclose administering to a mammal in need of
suppressing inflammation an antibody or a fragment thereof that specifically
binds to placental growth factor and that neutralizes the activity of placental
growth factor. Id. at 10.
Appellants point to page 187 of Bottomley, upon which the Examiner
relies, and which discloses:
We suggest that specific modulation of VEGF and P1GF is a
rational therapeutic target for inhibition of angiogenesis in the
joint. In the immediate future, this could be achieved by direct
injection into the joint of neutralizing humanized anti-VEGF and
anti-PIGF antibodies, or better still, injection of recombinant
soluble flt-1 receptor which would potentially neutralize both
factors. In the long term, orally active signal transduction
inhibitors that block the down-stream consequences of VEGF
and P1GF receptor triggering may prove to be the effective
angiogeneisis suppressive agents in clinical practice.
App. Br. 10-11 (emphasis added, internal reference omitted). Appellants
argue Bottomley does not place the presently claimed methods in the hands
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Application 13/785,253
of the public, as they contend would be required to anticipate the claimed
invention. Id. at 11.
We agree with the Examiner. “[Invalidity based on anticipation
requires that the assertedly anticipating disclosure enabled the subject matter
of the reference and thus of the patented invention without undue
experimentation.” Elan Pharms., Inc. v. Mayo Foundation for Med. Educ.
and Research, 346 F.3d 1051, 1052 (Fed. Cir. 2003). Furthermore: “A
claimed invention cannot be anticipated by a prior art reference if the
allegedly anticipatory disclosures cited as prior art are not enabled.” Amgen,
Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354 (Fed. Cir. 2003);
see also Bristol-Myers Squibb v. Ben Venue Labs., Inc., 246 F.3d 1368,
1374 (Fed. Cir. 2001) (“To anticipate, the reference must also enable one of
skill in the art to make and use the claimed invention”).
Section 112 requires that the patent specification enable “those skilled
in the art to make and use the full scope of the claimed invention without
‘undue experimentation’” in order to extract meaningful disclosure of the
invention and, by this disclosure, advance the technical arts. Invitrogen
Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070—71 (Fed. Cir. 2005).
We are not persuaded by Appellants’ arguments that the disclosures of
Bottomley at page 187 fail to anticipate the claims on appeal because we
find the recited passage enables the claimed invention. The cited disclosure
of Bottomley provides sufficient disclosure to allow a person skilled in the
art to make and use the full scope of the claimed invention, i.e., “administer[
] to a mammal ... an antibody or a fragment thereof that specifically binds
to placental growth factor and that neutralizes the activity of placental
growth factor,” without undue experimentation.
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In particular, Bottomley teaches the target population, “a mammal in
need of suppressing inflammation,” by specifically recognizing “P1GF may
therefore play a key role in the production of VEGF in the inflammatory
joint” of rheumatoid arthritis patients. See Bottomley, abstract. Bottomley
also teaches “pharmacological inhibition of angiogenesis resulting in
suppression of arthritis has been reported in experimental models” and “this
could be achieved by direct injection into the joint of neutralizing humanized
anti-VEGF and anti-PIGF antibodies.” Bottomley 187, col. 1. Thus,
Bottomley suggests suppressing rheumatoid arthritis, an inflammatory
condition in a mammal, by treatment of specific anti-PLGF antibodies that
neutralize placental growth factor, satisfying the elements of claim 1.
We therefore agree with the Examiner that the cited disclosure of
Bottomley is sufficiently enabled because it would tell a person of ordinary
skill in the art how to practice Appellants’ claims without undue
experimentation. Because we find Bottomley discloses an enabled
disclosure we affirm the Examiner’s rejection of the claims.
B. Rejection of claims E 2, 4, 5, 7, and 9 under 35 U.S.C. $ 103(a)
Issue
Appellants argue the Examiner erred because the alleged deficiencies
of Bottomley, related by Appellants supra, are not cured by the teachings or
suggestions of Shitara, Boulton, and Ferrara. App. Br. 13.
Analysis
Appellants argue that, as acknowledged by the Examiner, “Shitara et
al. differs from the claimed methods by not teaching employing anti-
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placental growth factor antibodies (P1GF) as a means of treating pathological
conditions involving VEGF.” App. Br. 13 (quoting Final Act. 7). Further,
argue Appellants, the Examiner acknowledges that Shitara does “not teach
employing anti-placental growth factor antibodies (P1GF) as a means of
treating pathological conditions involving” transforming growth factor-beta
(TGF-P) or tumor necrosis factor-alpha (TNF-a).” Id. (citing Bottomley
187).
Appellants dispute the Examiner’s finding that an “antibody or a
fragment thereof that specifically binds to placental growth factor and that
neutralizes the activity of placental growth factor,” as required by the
Appellants’ invention, is “equivalent” to an antibody that might specifically
bind VEGF, as taught by Shitara. App. Br. 13 (citing Final Act. 7).
Appellants contend that Boulton fails to teach or suggest that P1GF is
a consequence of proliferative diabetic retinopathy (“PDR”) or one of many
possible causes of PDR. App. Br. 14. According to Appellants, in the
absence of demonstration of such a causative relationship in the prior art, a
person of ordinary skill would not have expected the removal of P1GF to
effectively treat PDR. Id. Furthermore, Appellants argue, Boulton’s
teachings that: “inhibitors of P1GF ... are able to reduce, prevent or regress
ocular angiogenesis” and that “P1GF and functional derivatives or fragment
thereof may also be used to prevent ocular revascularization in conditions
such as the PDRs, ...” are contradictory with respect to whether P1GF
activity should be decreased or increased in order to prevent ocular
angiogenesis. Id. at 14—15 (citing Boulton 3, 4). Appellants, therefore,
argue that a person of ordinary skill would not, having understood the
combined cited prior art, including Boulton, have a reasonable expectation
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of therapeutic success in any modulating P1GF in an eye disorder such as
PDR. Id. at 15.
Appellants argue further that Ferrara teaches: “a thorough knowledge
of the signal transduction pathways of VEGFs and angiopoietins is essential
for their use in therapeutic settings.” App. Br. 15 (quoting Ferrara 1359).
Appellants contend Boulton neither teaches nor suggests these basic criteria
described by Ferrara, rather, Appellants argue the disclosures of Appellants’
Specification is based on thorough analysis of P1GF-/- knockout mice
challenged with multiple pathologies and reproduction of the knockout
phenotypes with an antibody neutralizing P1GF activity. Id.
Appellants argue further that Ferrara teaches a further alleged isoform
of VEGF, VEGF-E, which is known to bind PDGF receptors. App. Br. 16
(citing D.G. Gilbertson et al., Platelet-derived Growth Factor C (PDGF-C),
a Novel Growth Factor That Binds to PDGF a andReceptor, 276 (29) J.
Biol. Chem. 27406—14 (2001) (“Gilbertson”)). Appellants therefore
contend Ferrara relates to a signaling pathway that is unrelated to P1GF and
is therefore irrelevant to Appellants’ claimed invention. Id.
The Examiner responds that Shitara teaches methods of treating
diseases associated with VEGF, which can form P1GF-VEGF dimers (see
Bottomley Abstr.), including rheumatoid arthritis with antagonistic
antibodies, including monoclonal and humanized antibodies as well as the
claimed antigen-binding fragments. Ans. 8—9 (citing Shitara generally and
specifically cols. 8—28). The Examiner acknowledges Shitara does not teach
employing anti-PIGF antibodies as the means of treating pathological
conditions involving VEGF. Id. at 9. However, the Examiner finds
Bottomley teaches targeting P1GF for inhibition of pathological angiogenesis
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that fuels inflamed joints in patients with rheumatoid arthritis by neutralizing
humanized anti-PIGF antibodies. Id. (citing Bottomley 187).
The Examiner finds Boulton teaches inhibitors of P1GF in treating
pathological conditions encompassed by the claimed methods and described
in Appellants’ Specification, as well as teaching that neutralizing antibodies
against P1GF as inhibitors of P1GF. Ans. 9 (citing, e.g., Boulton 3—7;
Examples 1,2; Claims). With respect to Appellants’ argument that the
teachings of Boulton are contradictory, the Examiner finds Boulton teaches
that P1GF or functional derivatives/fragments may be used to stimulate or
inhibit angiogenesis depending upon the specific condition to be treated and
that there is no ambiguity about neutralizing antibodies against P1GF as
inhibitors of various pathological conditions. Ans. 9—10.
The Examiner also finds Ferrara teaches the use of antagonistic
antibodies to treat various diseases and conditions associated with VEGF,
including the use of polyclonal, monoclonal, humanized and human
antibodies as well as other modifications. Ans. 10 (citing, e.g., Ferrara cols.
54—59; 59-63). The Examiner finds, with respect to Appellants’ argument
that the teachings of Ferrara are not relevant because, in view of Gilbertson,
the Examiner relies on Ferrara as teaching generally the use of antagonistic
antibodies to treat various diseases and conditions associated with VEGF.
Id.
We are not persuaded by Appellants’ arguments. As we observed
supra, Bottomley explicitly teaches: “In the immediate future, this
[inhibition of P1GF- and VEGF-modulated angiogenesis] could be achieved
by direct injection into the joint of neutralizing humanized anti-VEGF and
anti-PIGF antibodies, or better still, injection of recombinant soluble flt-1
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receptor which would potentially neutralize both growth factors.”
Bottomley 187. We agree with the Examiner that Bottomley sets forth a
teaching or suggestion sufficient to establish obviousness to a person of
ordinary skill in the art. Furthermore, Boulton explicitly teaches the use of
anti-PIGF antibodies as a means of treating “conditions at least partially
characterised by abnormal ocular angiogenesis such as retinal
neovascularisation, subretinal neovascularisation, glaucomatous
neovascularisation, rubeosis or corneal neovascularization” by blocking
antibody binding activity. See Boulton, Abstr., 4—7, 12). We agree with the
Examiner that a person of ordinary skill, comprehending the teachings of the
combined cited prior art, would find it obvious to combine the references
and arrive at Appellants’ claimed invention.
With respect to Appellants’ argument that the disclosures of Boulton
are contradictory, we disagree. Boulton teaches:
The inventors[ ] have found that inhibitors of P1GF, which
are preferred modulators of P1GF activity, are able to reduce,
prevent or regress ocular angiogenesis. The term “inhibitor” is
used herein to mean a compound which will reduce or limit the
physiological effect of P1GF at its receptor by decreasing the
amount of P1GF that is available for combination with its
receptor. For example, this may be achieved by preventing the
production or secretion of P1GF, degrading P1GF or sequestering
P1GF. These inhibitors of P1GF are useful for treating conditions
such as the VPRs (particularly the Proliferative Diabetic
Retinopathies (PDRs)) and for the reduction, prevention or
regression of subretinal neovascularisation, iris
neovascularisation resulting in glaucoma, rubeosis, cornea
neovascularisation and particularly retinal neovascularisation
and for modulating the rapid progression of diabetic retinopathy
that occurs in pregnant females with diabetes. . . .
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[T]he inhibitor may be an agent which prevents P1GF combining
with its receptor such as a neutrali[z]ing antibody against P1GF
(PLGF 1 or 2) or a soluble receptor for P1GF....
P1GF and functional derivatives or fragments thereof may
also be used for treating conditions at least partially characterised
by abnormal ocular angiogenesis. P1GF and functional
derivatives or fragments thereof may be used to stimulate or
inhibit angiogenesis depending upon the specific condition to be
treated. For instance, P1GF and functional derivatives or
fragments thereof may be used to promote revascularisation of
ischaemic retina (e.g. following venous occlusion and diabetes).
P1GF and functional derivatives or fragment thereof may also be
used to prevent ocular revascularisation in conditions such as the
PDRs, corneal neovascularisation, rubeosis, iris
neovascularisation resulting in glaucoma, preretinal
neovascularisation, choroidal (subretinal) neovascularisation as
well as in such conditions as retrolental neovascularisation which
occurs in retinopathy of prematurity or following vitrectomy for
PDR.
Boulton 3^4. We agree with the Examiner that reading this passage as a
whole, Boulton discloses that, in different circumstances, up or down
regulation of P1GF may be desirable and possible. In conditions such as
ischemic retina, angiogenesis is a desirable outcome that can be promoted by
using P1GF. However, it is also evident that, in cases where angiogenesis is
undesirable, inhibition of P1GF by inhibitory factors, including anti-PIGF
antibodies, can inhibit angiogenesis. See Medichem, S.A. v. Rolabo, S.L.,
437 F.3d 1157, 1165 (Fed. Cir. 2006) (A “given course of action often has
simultaneous advantages and disadvantages, and this does not necessarily
obviate motivation to combine.”). We are not persuaded, therefore, that the
disclosures of Boulton and the other prior art references cited by the
Examiner would not lead a person of ordinary skill in the art to Appellants’
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claimed invention. We therefore affirm the Examiner’s rejection of the
claims on this ground.
DECISION
The Examiner’s rejection of claims 1, 2, 4, and 5 as unpatentable
under 35 U.S.C. § 102(b) is affirmed.
The Examiner’s rejection of claims 1, 2, 4, 5, 7, and 9 as unpatentable
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)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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