Ex Parte Martin et alDownload PDFPatent Trial and Appeal BoardMay 11, 201713662793 (P.T.A.B. May. 11, 2017) Copy Citation 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 following e-mail address(es): docket @ LicensingLaw. net administration @LicensingLaw.net 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.) Appeal 2015-007446 Application 13/662,793 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).) 2 Appeal 2015-007446 Application 13/662,793 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 3 Appeal 2015-007446 Application 13/662,793 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.) 4 Appeal 2015-007446 Application 13/662,793 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 5 Appeal 2015-007446 Application 13/662,793 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.) 6 Appeal 2015-007446 Application 13/662,793 [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 7 Appeal 2015-007446 Application 13/662,793 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. 8 Appeal 2015-007446 Application 13/662,793 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 9 Appeal 2015-007446 Application 13/662,793 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).”).) 10 Appeal 2015-007446 Application 13/662,793 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). 11 Appeal 2015-007446 Application 13/662,793 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). 12 Appeal 2015-007446 Application 13/662,793 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 13 Appeal 2015-007446 Application 13/662,793 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). 14 Appeal 2015-007446 Application 13/662,793 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 15 Appeal 2015-007446 Application 13/662,793 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 16 Appeal 2015-007446 Application 13/662,793 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. 17 Appeal 2015-007446 Application 13/662,793 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). 18 Appeal 2015-007446 Application 13/662,793 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”). 19 Appeal 2015-007446 Application 13/662,793 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). 20 Appeal 2015-007446 Application 13/662,793 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). 21 Appeal 2015-007446 Application 13/662,793 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 22 Copy with citationCopy as parenthetical citation