Ex Parte Martin et al

Patent Trial and Appeal Board

May 11, 2017

13662793 (P.T.A.B. May. 11, 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.
13/662,793 10/29/2012 John Francis MARTIN Ark-GB0703683.3 6009
22925 7590 05/15/2017
PHARMACEUTICAL PATENT ATTORNEYS, LLC
55 MADISON AVENUE
4THFLOOR
MORRISTOWN, NJ 07960-7397
EXAMINER
SAOUD, CHRISTINE J
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
05/15/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN FRANCIS MARTIN and CHARLES HENRY RODECK1
Appeal 2015-007446
Application 13/662,793
Technology Center 1600
Before ERIC B. GRIMES, TIMOTHY G. MAJORS, and DAVID COTTA,
Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treating intra-uterine growth retardation, which have been
rejected as indefinite and nonenabled. We have jurisdiction under 35 U.S.C.
§ 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as Magnus Life Sciences Ltd.
(App. Br. 4.)
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STATEMENT OF THE CASE
Appellants’ “invention relates to the treatment of a disease associated
with retarded fetal growth in pregnancy.” (Spec. 1:11—12.) According to
the Specification:
Pregnancy is associated with an enormous increase in uterine
perfusion, which results from increased maternal cardiac output
and trophoblast-driven modification of the uterine spiral arteries.
Failure of this normal physiological process is implicated in the
aetiology of two of the most challenging obstetric complications,
pre-eclampsia (PET) and fetal growth restriction (FGR), also
called intra-uterine growth retardation (IUGR).
(Id. at 1:14—18.)
The Specification discloses the “invention is based on a study”
that demonstrates for the first time in an in vivo animal model,
that adenovirus-mediated local overexpression of VEGF
[vascular endothelial growth factor] results in increased uterine
blood flow and relaxation of the uterine arteries. Low VEGF
levels and reduced uterine blood flow are implicated in the
aetiology of FGR. These results suggest therapeutic utility by
increasing VEGF expression, to improve the outcome of
pregnancies complicated by severe FGR.
(Id. at 2:2-7.)
Claims 1,2, and 7 are on appeal. Claim 1 is illustrative:
1. A method for providing treatment for intra-uterine growth
retardation, wherein said method comprises administering to
the uterine artery of a pregnant female in need of such
treatment, an agonist of VEGF receptor.
(App. Br. 26 (Claims App’x).)
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The claims stand rejected as follows:
I. Claims 1,2, and 7 under 35U.S.C. § 112, second paragraph
(pre-AIA), for indefmiteness.
II. Claims 1, 2, and 7 under 35 U.S.C. § 112, first paragraph (pre-
AIA), for failure to comply with the enablement requirement.
I-DEFINITENESS
Claim 1
Claim 1 recites, among other limitations, “administering ... an
agonist of VEGF receptor.” (App. Br. 26 (emphasis added).)
The Examiner finds that claim 1 “seems to imply that there is a single
receptor that is a VEGF receptor” but, because there are several known
VEGF receptors, “it is not clear which receptor the claim intends.” (Ans. 2.)
Further, the Examiner finds, because “[t]he claim does not use an article
[e.g., “a” or “the”] preceding ‘VEGF receptor’,... the claim language of
‘VEGF receptor’ is interpreted as a single entity.” (Id. at 7.) The Examiner
asserts that if Appellants intended a different meaning, they should clarify
by claim amendment. (Id. at 7—8.)
We are not persuaded. The Examiner’s interpretation of claim 1 as
limited to a single receptor is too narrow. The broadest reasonable
interpretation of the phrase “an agonist of VEGF receptor” encompasses an
agonist of at least one VEGF receptor. We conclude this meaning would be
reasonably clear to the skilled person in view of the Specification, which
recites, inter alia, “a VEGF agonist is a molecule, which binds to a receptor
to which VEGF binds. In particular, an agonist may bind to the flk-l/KDR
or fit-1 receptors.” (Spec. 2:13—14.) In expressly identifying at least these
two VEGF receptors, we agree with Appellants that the skilled person would
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not interpret claim 1 as encompassing only one-singular VEGF receptor.
(App. Br. 10.)
Claim 2
Claim 2 depends from claim 1 and recites “wherein said agonist
comprises polypeptide.” (App. Br. 26.)
The Examiner finds “the way the claim is written, it appears to be a
composition that ‘comprises polypeptide’ . . . [yet] [i]t is not even clear if the
agonist is a polypeptide or the composition just comprises polypeptide.”
(Ans. 3.)
We are unpersuaded. The Specification defines a VEGF agonist as a
“molecule” that binds to a receptor to which VEGF binds. (Spec. 2:13—14
(“As used herein, a VEGF agonist is a molecule, which binds to a receptor to
which VEGF binds.”) If by a “composition” the Examiner construes claim 2
as reading on simple mixtures that include a non-polypeptide agonist and
other non-agonist ingredients that happen to be polypeptides, we are
unpersuaded the Specification supports that interpretation. Rather, the
agonist’s molecular structure must include a polypeptide, but it need not be
limited to the polypeptide. As the Specification indicates, “[a] VEGF
agonist may have any chemical structure” and may, for example, be a
polypeptide modified by glycosylation, acetylation, etc. (Spec. 2:15—20.)
Claim 7
Claim 7 depends from claim 2 and recites “wherein said polypeptide
comprises VEGF or a fraction thereof which is an agonist of VEGF
receptor.” (App. Br. 26.)
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The Examiner finds the term “fraction” is indefinite and it is unclear
what term (“VEGF” or “fraction [of VEGF]”) the word “which” modifies.
(Ans. 3.)
Appellants argue claim 7 is unambiguous when read in context. (App.
Br. 11—12.) According to Appellants, the Specification discloses truncated
VEGF polypeptides and this is what is meant by “fraction[s].” (Id.)
Appellants also contend the claim reads on VEGF or fractions of VEGF and,
whichever is present, it must be “an agonist of VEGF receptor.” (Id. at 11.)
Appellants have the better position. We are unpersuaded the skilled
person would be unable to understand the metes and bounds of claim 7 when
read in light of the Specification, ft is reasonably clear the phrase “fraction
thereof’ refers to truncated forms or fragments of VEGF, and that VEGF or
these “fractions” must be VEGF-receptor agonists. (See Spec. 2:13—20.)
For the reasons above, we reverse the Examiner’s rejections of claims
1, 2, and 7 under 35 U.S.C. § 112, second paragraph, for indefmiteness.
11 — ENABEEMENT
Issue
According to the Examiner, Appellants’ Specification “demonstrated
a method for increasing blood flow in an artificially occluded uterine artery
by administration of nucleic acid encoding VEGF-A” but “[t]he
specification does not use a fetal growth restricted model.” (Ans. 4—5.) The
Examiner finds, “[bjecause no information is provided on effects of
administration on the fetus, it not known if VEGF administration is capable
of treating intra-uterine growth retardation.” (Id. at 4.)
Regarding the breadth of the claims and the Specification’s guidance,
the Examiner makes several additional findings. The Examiner finds “the
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claims are overly broad with regard to what agonist is being administered.”
{Id. at 5.) According to the Examiner, “[t]he specification teaches
administration of polynucleotides encoding two different VEGF peptides,
VEGF-A and VEGF-D . . . [but] the specification does not show any
beneficial effect of administering a nucleic acid encoding any VEGF peptide
other than VEGF-A.” {Id.)2 The Examiner finds “[t]he [claimed] method
includes any VEGF molecule while the specification only teaches that
VEGF-A was effective in increasing uterine blood flow.” {Id. at 23.)
To further illustrate the breadth of the claims versus the
Specification’s disclosure, the Examiner finds the claims read on, for
example, intravenous administration of a polypeptide agonist but the
Specification provides no examples or teachings sufficient to guide the
skilled person in carrying out such a method.3 {See Ans. 5, 18—19, 23—24;
see also Final Act. 15—16.) According to the Examiner,
2 The Examiner finds, for example, “[t]here are at least 6 different VEGF
molecules (A-E and PIGF) which bind with different affinities to 3 different
types of VEGF receptors (VEGFR1-3).” (Ans. at 22—23.)
3 The Examiner uses this example to distinguish from the working example
described in the Specification where a viral construct encoding VEGF-A
was injected into the temporarily occluded uterine artery in female sheep in
order to provide for local overexpression of VEGF-A in the artery. {See
Spec. 2:3—4 (“adenovirus-mediated local overexpression of VEGF results in
increased uterine blood flow and relaxation of the uterine arteries.”).) As
Appellants’ declarant Anna L. David, Ph.D. explains, the gene-therapy
occlusion model described in the Specification was used to increase
transfection efficiency at the intended transfection/expression site (i.e.,
uterine artery), and to prevent the vector from washing away from the
uterine artery resulting in systemic gene transfer. {See Declaration of Anna
L. David, Ph.D. dated Jan. 5, 2012 (“David Deck”) 2.)
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[w]hile an effect was seen with vector-containing VEGF-
encoding nucleic acid [in Appellants’ Specification] presumably
due to increased expression of VEGF in the uterine artery, it is
not clear how one would administer a polypeptide agonist to the
uterine artery in such a manner that intra-uterine blood flow
would be increased. One cannot administer the polypeptide
intravenously and expect it to arrive at the required site of action
in an amount sufficient to have a physiological effect.
(Ans. 5.) The Examiner finds “simple injection or IV infusion would not be
sufficient because the protein needs to act on the uterine artery and not the
rest of the maternal vasculature.” {Id. at 24.) And, according to the
Examiner, “[t]he experiments which are presented are not predictive of [] the
compound to be used in the claimed method (administration of protein
versus the gene therapy technique exemplified in the example.)” {Id. at 14.)
Put differently, apart from the vector construct in the Specification’s lone
working example, the Examiner finds the Specification “fails to teach how
VEGF protein will be administered such that it is delivered to its proper site
of action and in a manner such that it is therapeutically effective (i.e. in a
proper dose for a proper duration of time).” (Final Act. 15—16.)
The Examiner also finds the claims are not limited to treating
intrauterine growth retardation caused by any particular disease or condition.
(Ans. 16.) According to the Examiner, “while [IUGR] is most commonly
caused by inadequate maternal-fetal circulation, there are other causes which
are not related to circulation” such as congenital anomalies. {Id. (citing
Vandenbosche4); see also id. at 5—6.) So, the Examiner reasons, “[i]f the
4 Vandenbosche, et al., Intrauterine Growth Retardation, 58:6 American
Family Physician 1384—90 (1998) (“Vandenbosche”). The record copy of
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cause of the fetal growth retardation is not related to blood flow, one of
ordinary skill in the art would not expect an increase in blood flow to treat
the condition.” (Id. at 15.)
The Examiner finds that undue experimentation would, thus, be
needed to make and use the full scope of the claims. According to the
Examiner, “the various VEGF family members have different receptor
specificities, [and] it is not clear which VEGF protein would be useful in the
claimed method.” (Final Act. 15.) Also, the Examiner finds, “VEGF-A is
clearly not representative of all agonists of VEGF receptors or representative
of all polypeptide agonists of VEGF receptors as ‘agonist’ could encompass
any molecule that agonizes the VEGF receptor and is not limited to VEGF
proteins.” (Id.) The Examiner finds “the skilled artisan would need to
devise a method of administration of VEGF [beyond the Specification’s
vector occlusion model] such that it was delivered to the uterine arteries in a
sufficient amount for a sufficient period of time to affect the uterine
vasculature.” (Ans. 19.) And, the Examiner explains, “this experimentation
would be considered undue because there is no guidance in the instant
specification with regard to how this is to be accomplished and there is no
reasonable expectation of success that it could be achieved.” (Id. at 19—20.)
Appellants contend the claims are enabled and raise several
arguments. Appellants argue, inter alia: (i) “the inventors teach at least one
way of making and using the claimed invention” and no more is required
(App. Br. 13); (ii) “[e]nablement does not require showing an effect on the
Vandenbosche appears to be a web archive (available at
http://www.aafp.org/afp/981015ap/vandenbo.html) without page numbers.
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fetus because enablement does not require actual reduction to practice” (id.
at 16); (iii) “FGR is caused by inadequate blood supply” (id. at 18) and the
Examiner cannot rely on other potential causes due to res judicata arising
from prosecution of a related application (id. at 18—19), and; (iv) the
inventors need not enable what they do not claim. (Reply Br. 12—14.)
The issue with respect to this rejection is: has the Examiner
established by a preponderance of the evidence that the Specification does
not enable the claimed invention?
Principles of Law
When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the specification of
the application.
In re Wright, 999 F.2d 1557, 1561—62 (Fed. Cir. 1993). “[T]o be enabling,
the specification of a patent must teach those skilled in the art how to make
and use the full scope of the claimed invention without ‘undue
experimentation.’” Id. at 1561 (citation omitted).
Factors to be considered in determining whether a disclosure
would require undue experimentation... include (1) the quantity
of experimentation necessary, (2) the amount of direction or
guidance presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the state of the prior
art, (6) the relative skill of those in the art, (7) the predictability
or unpredictability of the art, and (8) the breadth of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). In addition,
the scope of the claims must bear a reasonable correlation to the
scope of enablement provided by the specification to persons of
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ordinary skill in the art. In cases involving predictable factors,
such as mechanical or electrical elements, a single embodiment
provides broad enablement in the sense that, once imagined,
other embodiments can be made without difficulty and their
performance characteristics predicted by resort to known
scientific laws. In cases involving unpredictable factors, such as
most chemical reactions and physiological activity, the scope of
enablement obviously varies inversely with the degree of
unpredictability of the factors involved.
In re Fisher, 427 F.2d 833, 839 (CCPA 1970).
Analysis
Appellants argue the patentability of claims 1, 2, and 7 as a group.
We select claim 1 as representative. For the reasons discussed below, we
agree with the Examiner that the Specification does not provide a sufficient
enabling disclosure for claim 1.
As the Examiner notes, no IUGR5 test model is described in the
Specification. (See, e.g., Ans. 11 (“The examiner could not find any
mention of inducing FGR in the pregnant ewes prior to VEGF vector
administration.”).) Rather, the Specification’s “study” showed a statistically
significant increase in uterine blood flow following injection of an
adenovirus vector encoding VEGF-A into a temporarily occluded uterine
artery of pregnant sheep. (Spec. 4—9.) In the study, a single subject was also
injected with a vector encoding VEGF-D, but no increase in uterine blood
flow was observed. (Id. at 9:3 4.) But the study neither indicates whether
the sheep were exposed to conditions causing IUGR nor tests the fetuses for
5 As in Appellants’ Specification, FGR and IUGR are used interchangeably
herein. (See Spec. 1:17—18 (“fetal growth restriction (FGR), also called
intra-uterine growth retardation (IUGR).”).)
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IUGR. In discussing the study results, the Specification discloses “[t]his
increase in blood flow may be sufficient to achieve an increase in fetal
growth and allow delivery of the baby at a birth weight and gestational age
that is compatible with survival.” (Spec. 10:19—21.)
The Examiner’s findings with respect to the absence of an IUGR-
animal model in the Specification do not, however, alone persuade us that
claim 1 is nonenabled. Appellants provided declaratory evidence in
response. This evidence includes testimony and data from Dr. David
showing that, in an IUGR model,6 administration of the VEGF-A gene
therapy construct to pregnant sheep did result in increased fetal abdominal
circumference and renal volume, as well as increased birth weight, and
gestation time. (David Decl. 6—12.) Appellants also provide testimony of
inventor John F. Martin, M.D. that “[w]e do not teach the effect of blood
flow on the fetus because the skilled artisan already knows that reduced
uterine blood flow is linked to IUGR.” (See Martin Decl. 4.)7 The
publications Dr. Martin cites in support corroborate his testimony. (See,
e.g., Lang8 Abstract (“uterine blood flow is inextricably linked to fetal
growth and survival”), S55 (“Inadequate uteroplacental perfusion during
pregnancy therefore is considered to be one of the most likely and important
6 Dr. David states that “[i]n this particular model, the over-nourished
adolescent sheep, there is an approximate 40% reduction in uterine blood
flow mid-gestation, which degree correlates with the degree of fetal growth
restriction.” (David Decl. 6—7.)
7 Declaration of John F. Martin, M.D. dated December 23, 2011 (“Martin
Decl.”).
8 Lang et al., Uterine blood flow—a determinant offetal growth, 110
European J. of Obstetrics & Gynecology and Reproductive Biology,
S55-S61 (2003).
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causes of IUGR”), Fig. 2 (showing the correlation between average uterine
blood flow and fetal weight).)9 Accordingly, although the Specification
lacks an IUGR model and is somewhat equivocal in stating that “[t]his
increase in blood flow may be sufficient to achieve an increase in fetal
growth,” the preponderance of the evidence suggests a skilled person would
have reasonably predicted a significant increase in uterine flow to increase
birth weight and gestational age, thus providing treatment for IUGR.
Neither are we persuaded that claim 1 fails the enablement
requirement simply due to other potential causes of IUGR. (Ans. 16.) The
preponderance of the evidence suggests the most prevalent and significant
cause of IUGR is inadequate maternal-fetal circulation. (See, e.g.,
Vandenboschepassim', see also Lang S55.) That cause is the focus of
Appellants’ Specification. Thus, even if Appellants’ method did not work in
treating IUGR arising from causes like a congenital anomaly (see
Vandenbosche Table 1), we are unpersuaded that this alone would cause
claim 1 not to meet the enablement requirement. See Atlas Powder Co. v.
E.I. Du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984)
(“Even if some of the claimed combinations were inoperative, the claims are
When we consider these reasons together with the other reasons
provided by the Examiner, however, we are persuaded that claim 1 fails the
enablement requirement. More specifically, claim 1 is extremely broad with
9 “[Section] 112 requires that, unless the information is well known in the
art, the application itself must contain this information; it is not sufficient to
provide it only through an expert’s declaration.” In re Buchner, 929 F.2d
660, 661 (Fed. Cir. 1991).
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respect to the agonists and VEGF receptors that are recited, and the
Specification fails to provide an enabling disclosure commensurate with this
scope. To comply with the enablement requirement
[t]here must be sufficient disclosure, either through illustrative
examples or terminology, to teach those of ordinary skill [in the
art] how to make and how to use the invention as broadly as it is
claimed. This means that the disclosure must adequately guide
the art worker to determine, without undue experimentation,
which species among all those encompassed by the claimed
genus possess the disclosed utility.
In re Vaeck, 947 F.2d 488, 496 (Fed. Cir. 1991) (footnote omitted); see also
National Recovery Technols. Inc. v. Magnetic Separation Sys., Inc., 166
F.3d 1190, 1195—96 (Fed. Cir. 1999) (“The enablement requirement ensures
that the public knowledge is enriched by the patent specification to a degree
at least commensurate with the scope of the claims. The scope of the claims
must be less than or equal to the scope of the enablement.”)
The guidance and examples provided in the Specification are limited
to particular agonists (vector construct encoding VEGF-A or VEGF-D). Yet
the claims cover much more. As the Examiner points out, the claimed
“agonist” may be any molecule that binds to a VEGF receptor. (Ans. 5, 23.)
The Specification discloses that “agonists” may be peptides, polypeptides, or
truncated forms with, for example 10, 20, 50, or 100 residues. (Spec. 2:15-
lb.) The Specification lists further preferred agonists including modified
peptides or peptoids (for example, modified by glycosylation, sulphation,
and acetylation, among others), non-peptide molecules, mimics, naturally
occurring or engineered VEGF proteins, and gene constructs encoding
VEGF peptides. Even limiting the claim to common VEGF peptides, which
the Specification and claim 1 do not, there are at least at least 6 different
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VEGF families (VEGFA—E and PIGF) and numerous VEGF receptors to
which the VEGF peptides bind with different affinity and specificity. (Ans.
22-23.)10
The working examples provided in Appellants’ Specification are also
limited to a particular method of administration (direct injection of an
artificially occluded uterine artery with the VEGF-A or VEGF-D vector
construct). Here again, claim 1 is much broader. Claim 1 encompasses, for
example, systemic/intravenous administration of exogenous polypeptide
agonists. (Spec. 2:31—3:1 (“VEGF agonist may be delivered to a blood
vessel, preferably an artery, in any suitable form.”) Claim 1 does not require
direct injection of the agonist into the uterine artery — occluded or
otherwise. And Appellants’ examples and data only show direct injection of
a vector construct into an occluded artery to ensure local overexpression of
the agonist at that site.
In sum, the Specification provides insufficient disclosure to show that
the results exhibited with the particular viral construct and route of
administration apply to the full scope of claim 1. Claim 1 encompasses any
molecule that binds to a VEGF receptor. But, even accepting Appellants’
post-filing testing and data offered in support of enablement, Appellants
10 See also Brownbill et al., Vasoactive and Permeability Effects of
VEGF 165 in the Term In vitro Dually Perfused Human Placental Lobule,
endocrinology 1—55, 3 (July 19, 2007) (manuscript) (“VEGF has several
family groups but it is the VEGF-A family that is principally involved in the
regulation of vasoactive tone. VEGF-A has at least seven splice variants:
VEGF-121, -145, -148, -165, -183, -189, and -206 .... Several receptors
exist for VEGF: VEGFR-1, VEGFR-2, VEGFR-3, neuroplilin 1,
neuroplilin-2 and soluble VEGFR-1 (sVEGFR-1).”) (internal citations
omitted).
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provide evidence only with respect to administration of VEGF-A and
VEGF-D. Appellants fail to persuasively rebut the Examiner by providing
evidence that the increased uterine blood flow observed with VEGF-A and
VEGF-D would reasonably be expected to be found, or could be determined
without undue experimentation, across the broad range of agonists and
receptors encompassed by claim 1. Appellants also fail to show the data
described in the Specification (and declaration evidence) is not unique to
using viral constructs directly injected into an occluded uterine artery — a
route of administration intended to ensure local (as opposed to systemic)
overexpression of the agonist. That is not to say that enablement by
Appellants’ Specification requires detailed testing for every variation of
agonist and route of administration covered by claim 1, but we are not
persuaded that routine testing or general knowledge of an ordinarily skilled
person make up for the lack of information provided in the Specification.
As the Examiner determined, based on the limited guidance provided, it
would require undue experimentation to carry out the method of claim 1
with, for instance, IV infusion of polypeptide agonists. (Ans. 5, 23—24.)
Appellants provided insufficient persuasive evidence to the contrary.
We further address the Appellants’ arguments below.
Appellants argue the enablement requirement is met because the
Specification discloses at least one method of making and using the
invention. (App. Br. 13.) Appellants refer to the Specification’s study,
which, as discussed above, was limited to injecting a vector construct
encoding VEGF-A (or VEGF-D) into an artificially occluded uterine artery.
(Spec. 4—10.) We are unpersuaded the Specification’s limited disclosure
enables the full scope of claim 1. See In re Fisher, 427 F.2d at 839; see also
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Automotive Technologies Intern., Inc. v. BMW of North America, Inc., 501
F.3d 1274, 1285 (Fed. Cir. 2007) (“We also reject [plaintiffs] argument that
because the specification enables one mode of practicing the invention, viz.,
mechanical side impact sensors, the enablement requirement is satisfied.”);
Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 1378—1379 (Fed. Cir.
2007) (holding that the specification did not enable an injector without a
pressure jacket even if injector with a pressure jacket was enabled). The
method of claim 1 encompasses, for example, systemic/IV administration of
any exogenous polypeptide that binds to a VEGF receptor. But the
Specification provides insufficient specific direction how such a method
would be carried out to provide treatment of IUGR without undue
experimentation.
Appellants argue the occlusion model described in the Specification
does not provoke IUGR and that the inventors induced IUGR in pregnant
sheep using known means. (App. Br. 13—14.) We agree with Appellants
that the occlusion model was not used to cause IUGR — the model was used
to ensure transfection and local overexpression of the agonist within the
uterine artery. (David Deck 2.) It does not, however, appear that IUGR was
induced in the Specification’s “study.” But, as discussed above, Appellants
provided other persuasive evidence regarding the link between insufficient
uterine blood flow and IUGR that was known in the art.
Appellants contend “[e]nablement does not require showing an effect
on the fetus because enablement does not require actual reduction to
practice.” (App. Br. 16.) And, in any event, Appellants contend they did
show an actual reduction to practice as evidenced by the Specification, Dr.
David’s data, and the prior art. (Id. at 17.) Even if the preponderance of the
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evidence shows enablement of a method of treating IUGR with a vector
construct encoding VEGF-A (or VEGF-D) injected into the uterine artery in
a manner causing local overexpression, we are unpersuaded the full scope of
claim 1 is enabled for reasons already explained.
Appellants argue IUGR is caused by inadequate blood supply and the
Examiner’s statements to the contrary are barred by res judicata. (App. Br.
19—20; Reply Br. 10-12.) Inadequate blood supply is the most prevalent
cause of IUGR, but there may also be causes like congenital anomalies that
do not clearly implicate blood supply. (Ans. 16.) The existence of other
uncommon causes unrelated to blood supply, however, is not decisive in our
analysis as explained above.
As to res judicata, it does not apply here for at least two reasons.
First, Appellants have not shown that an examiner in a separate
prosecution11 was “acting in a judicial capacity.” U.S. v. Utah Const. &
Min. Co., 384 U.S. 394, 422 (1966). Second, in the other prosecution, there
was no final judgment or specific finding on the issue. Appellants filed an
appeal brief raising an argument about causes of IUGR, along with several
other arguments. (See 3/15/2012 App. Brief 12—13 in the ’640 Application.)
The examiner in that prosecution did not file an answer. Rather, the
examiner proposed and entered an amendment substantially narrowing the
relevant claim (which has different and narrower language than pending
claim 1) and allowed the claim stating the following: “The enablement
rejection under 35 USC 112, 1st paragraph ... is withdrawn in light of the
11 Appellants refer to prosecution of U.S. Application No. 12/522,640 (“the
’640 Application”), which is related to the present application.
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declarations filed under 37 CFR 1.132 on 01/02/2012 and 01/06/2012 and
the [examiner’s] amendments to claim 1.” (See 10/15/12 Notice of
Allowability in the ’640 Application.) The matter never reached the Board,
and neither the Board nor the examiner made any “judgment” or specific
finding about the cause or causes of IUGR.12
Appellants argue administering a polypeptide requires only routine
skill. (App. Br. 20.) Appellants acknowledge that the “inventors’ data do
not. . . show administration of exogenous polypeptide” but contend the
inventors say “VEGF would be expected to work the same whether it comes
from [e.g.,] a surgical sponge or a transfected cell.” (Id.) Appellants do not,
however, direct us to any disclosure in the Specification or persuasive
evidence that adequately supports this expansive contention. As noted
above, the Examiner distinguished administration by the narrower vector
construct and administration of exogenous polypeptide agonists through, for
example, IV injection into the systemic circulation, and provided a reasoned
explanation why determining therapeutic effect in this latter case would
require undue experimentation. (See Ans. 5, 23—24; Final Act. 15—16.)
Appellants argue that one non-responsive subject does not show
nonenablement. (App. Br. 21—23.) More specifically, Appellants refer to
the single sheep given a vector encoding VEGF-D in the Specification’s
testing, which did not show an increase in uterine blood flow. (Id. at 21—22;
see also Reply Br. 8—10.) According to Appellants, “the particular test
subject was non-responsive to gene therapy of any kind” and thus, at most,
12 Cf. In re Hutchison, 154 F.2d 135, 137 (CCPA 1946) (claims in each
application are examined for patentability on their own merits).
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the data is merely inconclusive. (Id. at 22; David Decl. 3 4.) The one
alleged non-responsive subject aside, Appellants provided evidence that
VEGF-A and VEGF-D are structurally and functionally similar and provide
post-filing data showing an increase in arterial dilation and blood flow (like
shown with VEGF-A in the Specification) with VEGF-D constructs. (See
Martin Decl. 4; David Decl. 4—6.) The Examiner asserts that Dr. David’s
testing on VEGF-D is unclear in some respects. (Ans. 20—21 (“it is not clear
if it is from a pregnant or non-pregnant subject”).)13 But the preponderance
of the evidence on this issue favors the Appellants. Appellants persuasively
established that skilled artisans would have reasonably predicted that
administration of VEGF-D gene therapy would have been expected to work
like the VEGF-A gene therapy described in the Specification. However,
while the preponderance of the evidence favors the Appellants with respect
to VEGF-D therapy, for the reasons already discussed, the full scope of
claim 1 is nonenabled.
We address Brownbill14 in view of the argument provided in the
Reply Brief and the apparent confusion that arose due to there being
multiple Brownbill references. (App. Br. 15; Reply Br. 5—6; Ans. 13.)
Appellants argue Brownbill does not show undue experimentation with
Appellants’ method, contrary to the Examiner’s assertions. (Reply Br. 5.)
13 To the extent there were questions about Appellants’ testing, the Examiner
has the authority to require information under 37 C.F.R. § 1.105(a)(1).
14 Brownbill et al., The Vasodilatory Response To Vascular Endothelial
Growth Factor (VEGF) In the Fetoplacental Vasculature Of The In Vitro
Dually Perfused Placental Lobule Is Potentiated In Intrauterine Growth
Restriction (IUGR) and Preeclampsia (PE), 13 J. Soc. Gynecol. Investig.
228A, Abstract #500 (Feb. 2006) (“Brownbill”).
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Brownbill teaches that “the sensitivity of IUGR and PE fetoplacental
vasculature to exogenous VEGF165 was reduced compared to perfused
lobules from healthy pregnancy” and that “the responsiveness of the
fetoplacental vasculature to VEGF is altered in IUGR and PE.” (Brownbill.)
In other words, IUGR vasculature is different from healthy vasculature and
less responsive to VEGF165, and this suggests some unpredictability when
treating the IUGR vasculature. As Appellants point out, however, Brownbill
states “VEGF might increase the blood flow through this circulation in these
conditions of pregnancy” (Brownbill) and Appellants emphasize Brownbill
does not state “VEGF might not work.” (Reply Br. 5.) Brownbill is unclear;
“might” conveys a possibility yet it could mean it is possible but unlikely.15
We have reviewed Brownbill and the contentions about it, but Brownbill
does not sway the analysis significantly one way or the other.
Appellants argue they need not enable what they do not claim. (Reply
Br. 12—14.) First, Appellants contend the claims require “administering to
the uterine artery” and “i.v. infusion either gets our agonist to the uterine
artery, or it doesn’t.” (Id. at 12.) This argument elides the Examiner’s point,
which is that the claims encompass both direct and indirect routes of
administration. (Final Act. 15—16.) For example, claim 1 may cover
injection of a vector construct directly into an occluded uterine artery (like
the working examples and Appellants’ post-filing data) or IV delivery of
15 See https://www.merriam-webster.com/dictionary/might (“might” (past of
may) — “used as a helping verb to show that something is possible but not
likely”) (last visited May 3, 2017); see also
http://dictionary.cambridge.org/us/dictionary/english/might (“might” is
“used to express the possibility that something will happen or be done or is
true, although it may not be very likely”) (last visited May 3, 2017).
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protein such that it is distributed throughout the entire circulatory system.
Appellants’ Specification and testing fail to provide sufficient guidance how
the agonist could be administered to achieve a therapeutic effect beyond the
mode of administration that is exemplified and thus, according to the
Examiner, undue experimentation is required. (Id.; see also Ans. 5, 18—19;
23—24.) On this point, Appellants did not persuasively rebut the Examiner.
Second, Appellants argue “the inventors need not enable treatment of
IUGR because treatment is not part of the claimed invention.” (Reply Br. 13
(underlining and capitalization omitted).) According to Appellants
“providing treatment for intra-uterine growth retardation” appears in the
preamble of claim 1 and the Examiner is “reading unclaimed results into the
claims.” (Id.) Appellants’ argument is unpersuasive. The phrase “a
pregnant female in need of such treatment” is in the body of claim 1 and
relates back to the “treatment” recited in the preamble — without it, “such
treatment” makes no sense. Eaton Corp. v. Rockwell Int 7 Corp., 323 F.3d
1332, 1339 (Fed. Cir. 2003) (“When limitations in the body of the claim rely
upon and derive antecedent basis from the preamble, then the preamble may
act as a necessary component of the claimed invention.”) The phrase
“providing treatment for intra-uterine growth retardation” is a necessary
limitation of claim 1.
Conclusion of Law
We conclude the preponderance of the evidence supports the
Examiner’s determination that claim 1 is nonenabled.
Claims 2 and 7 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
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SUMMARY
We reverse the rejection of claims 1,2, and 7 under 35U.S.C. § 112,
second paragraph, for indefiniteness.
We affirm the rejection of claims 1,2, and 7 under 35U.S.C. § 112,
first paragraph, for lack of enablement.
TIME PERIOD FOR RESPONSE
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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