DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed 06/29/2026.
Claims 16, 22, 24-26, and 30-34 are pending in the application.
Applicant’s election without traverse of a transgene encoding CILP-1 in the reply filed on 12/31/2025 is acknowledged.
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/31/2025.
Claims 16, 22, 24-26, and 30-31 are amended, claims 17-21, 23, and 27-29 are cancelled, and claim 34 is newly added as set forth in the claim set filed 06/29/2026.
Therefore, claims 16, 24-26 and 30-34 are examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2021/065424 filed June 09, 2021.
Applicant’s claim for the foreign benefit of a prior-filed European Patent 20305625.4 filed June 09, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is June 09, 2020.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Specification
The objection to the disclosure is withdrawn as Applicant has amended paragraphs 0173 and 00051.
Claim Objections
The objection of claim 20 is withdrawn as Applicant has amended to spell out acronyms.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 28-29 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
Claims 28 and 29 have been canceled.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(a)
Claims 16, 25, 30-33 remain rejected and claims 24 and 34 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for
a method of reducing heart fibrosis via intravenous administration of an AAV9 vector with a hTnn2 promoter encoding a transgene to overexpress CILP, WISP2, DKK3 or SFRP2 at an effective dosage of 1 x 1013 vg/kg to a patient in need thereof,
does not reasonably provide enablement for
a method of treating genetic dilated cardiomyopathies in a patient in need thereof, comprising administering any dosage via any administration route to the patient.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. While applicant’s amendments partially overcome some of the issues, some additional issues remain that are discussed below.
The Breadth of the Claims and The Nature of the Invention
The independent claim is directed to a method of reducing fibrosis, the method comprising the step of administering a particular transgene encoding a CILP-1, DKK3, SRFP2, CCN5/WISP2 protein or an interfering RNA which decreases LTBP2 expression in an AAV particle at any dosage by any route of administration, thereby treating the subject.
While the specification discloses the pharmaceutical composition “may be administered by any convenient route, such as in a non-limiting manner by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and administration can be systemic, local, or systemic combined with local; systemic includes parenteral and oral, and local includes local and loco-regional. Systemic administration is preferably parenteral such as subcutaneous (SC), intramuscular (IM), intravascular such as intravenous (IV) or intraarterial; intraperitoneal (IP); intradermal (ID), epidural or else” (para. 000151), such is non-limiting.
The claims are broad for reasonably encompassing a multitude of anatomically and physiologically distinct administration routes, including, but not limited to, delivery and administration systemically, regionally or locally, or by any route, for example, by injection, infusion, orally, ingestion, inhalation, intranasal, intubation, intrapulmonary, intrapulmonary instillation, subcutaneously, and others.
No administration routes are recited in the claims, let alone the independent claim.
The claims are broad for reasonably encompassing a multitude of AAV capsid serotypes, including AAV1, AAV2, AAV3 (including types3A and 3B), AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV2i8, AAVrh10, AAVrh39, AAVrh43, AAVrh74, AAV-LK03, AAV2G9, AAV.PHP, AAV-Anc80, AAV3B and AAV9.rh74 (para. 00123).
Claim 30 recites a broad list of AAV-1, AAV-6, AAV-8, AAV-9 and AAV9.rh74 capsids serotypes.
Claim 31 recites AAV9.rh specifically.
The claims are broad for reasonably encompassing any expressible modulator of TGF-beta or WNT pathways including a transgene encoding a CILP-1, DKK3, SRFP2, CCN5/WISP2 protein. As disclosed in para. 0030 and 0031. This includes both activators and inhibitors. Moreover, the claim includes an interfering RNA which specifically decreases latent transforming growth factor beta binding protein 2 (LTBP2) expression, targeting components of the Wnt or TGF- R pathway. The invention encompasses recites “a functional variant thereof” broadly encompassing variants or derivative thereof (fragments, fusion proteins ; decoy receptors, soluble proteins, dominant negative mutants) and antibodies directed to components of the Wnt or 15TGFR pathway including fragments and expressible derivative thereof” as well as transgenes specifically (para. 0021, 0031).
The species election has directed the claims to a transgene.
The claims are broad for reasonably encompassing any dosage of AAV vector or modulator of the pathways. The specification only discloses dosages within the working examples of 1011 vg/mouse equivalent to 1013 vg/kg in a 20 g mouse (para. 0233). Newly added claim 34 recites “1013 vg/kg or more.”
The State of the Prior Art, The Level of One of Ordinary Skill and The Level of Predictability in the Art
Considering the mode of administration, the specification simply requires administration of the AAV to the subject by any means and any dosage. The art has demonstrated through numerous publications, delivery of nucleic acid vectors in vivo is highly unpredictable for successful human therapy.
Daya et al (Gene Therapy Using Adeno-Associated Virus Vectors, Clin. Microbiol. Rev. 21(4): 583-593, 2008; p. 590-591, joining ¶). When considering AAV therapy, there are many obstacles to its use systemically- host cell immune response which leads to toxicity (Daya et al, p. 587, col 2), blood brain as well as cellular barriers against the virus, adequate expression, degradation of the vector or the product. Even the use of targeting methods and tissue specific promoters have done little to overcome the numerous obstacles related to gene delivery. Even use of tissue specific promoters and capsids targeting has not successfully overcome these obstacles. Taken together with the large breadth of target tissues and diseases claimed, in light of the difficulties to overcome even one of these barriers, one could not perform the full breadth of the claims.
Therefore, it would be undue experimentation to utilize any means of administration with any dosage.
Tian et al (Aerosol Inhalation-mediated Delivery of an Adeno-associated Virus 5-expressed Antagonistic Interleukin-4 Mutant Ameliorates Experimental Murine Asthma, Archives of Medical Research 50: 384-392, 2019) is considered relevant art for having taught inhaled administration of rAAV, whereupon AAV vector DNA was detected in the lung, but not detected in other organs, such as heart, liver, kidney, brain, lymph nodes, and gonads (e.g. Abstract; p. 386, col. 2).
Therefore, administration routes such as inhalation would not be enabled for the present invention which targets the heart.
The Existence of Working Examples and The Amount of Direction Provided by the Inventor
The independent claims fail to recite the minimal AAV dosage required to achieve the therapeutic result.
The specification only discloses dosages within the working examples of 1011 vg/mouse equivalent to 1013 vg/kg in a 20 g mouse administered intravenously (para. 0233). The modulators administered are AAV9-hTnnt2-hCILP, AAV9-4inlshRNA-mLTBP2- GFP, AAV9- hTnnt2-hWISP2, AAV9-hTnnt2-hDKK3 and AAV9-hTnnt2-hSFRP2 (para. 00226, 00233)
The claims fail to recite, and the specification fails to disclose, a first modulator dosage administered via a first administration route, e.g. intravenously, that is necessarily and predictably able to treat dilated genetic cardiomyopathy, as opposed a second dosage administered via a second administration route, e.g. intranasally, that is unable to treat genetic dilated cardiomyopathy through reducing fibrosis, for example.
The Quantity of Any Necessary Experimentation to Make or Use the Invention
Thus, the quantity of necessary experimentation to make or use the invention as claimed, based upon what is known in the art and what has been disclosed in the specification, will create an undue burden for a person of ordinary skill in the art to demonstrate that the broadly claimed genus of rAAV serotypes, broadly claimed dosage which may be administered by the broadly encompassed administration routes so as to necessarily and predictably broadly reduce fibrosis in the heart.
Those of ordinary skill in the art would immediately recognize that the instant specification fails to establish the nexus between the broad genus of AAV vectors, the enormous genus of AAV vector dosages, and the corresponding enormous genus of anatomically distinct administration routes so as to necessarily and predictably achieve a real-world, clinically meaningful therapeutic result in subjects with any genetic dilated cardiomyopathy.
In conclusion, the specification fails to provide any guidance as to how an artisan would have dealt with the art-recognized limitations of the claimed method commensurate with the scope of the claimed invention and therefore, limiting the claimed invention to a method of reducing heart fibrosis via intravenous administration of an AAV9 vector with a hTnn2 promoter encoding a transgene to overexpress CILP, WISP2, DKK3 or SFRP2 at an effective dosage of 1 x 1013 vg/kg to a patient in need thereof, is proper.
In response to Applicant’s arguments and amendments filed 06/29/2026 regarding 112a Enablement,
Applicant’s arguments and amendments filed 06/29/2026 have been considered however, they are not persuasive.
Applicant argues that claim 16 reciting “therapeutically effective amount” and “AAV particle” overcome the 112a rejection previously set forth. Applicant states that the claims do not encompass an arbitrary dosage, but rather they are limited to dosages which achieve therapeutic effect and an artisan can find the dosages within the specification. Moreover, Applicant states that routes for administration are known in the art for cardiac gene therapy.
Examiner disagrees. “Therapeutically effective” does not describe the dosage in a way to not present undue burden and experimentation for an artisan to utilize the claimed invention. The claims themselves must be able to fully encompass the invention and not rely on reading limitations from the specification into them. Moreover, the breadth of administration is broader than what is described in the specification. Although there are administration routes known in the art, the scope of the claim is vast and encompasses more than what is known in the art and more than what is demonstrated in the working examples. The instant specification does not appear to teach reducing heart fibrosis in a patient in need thereof suffering from a genetic dilated cardiomyopathy by any route of administering an AAV particle composition comprising a therapeutically effective amount of a transgene encoding a CILP-1, DKK3, SRFP2, CCN5/WISP2 protein or an interfering RNA which decreases LTBP2.
Claim Rejections - 35 USC § 103
Claims 16, 30, and 32-33 remain rejected and claim 34 is newly rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Journal of Molecular and Cellular Cardiology Volume 116, March 2018, Pages 135-144 + Online Supplement) in view of Zhou (Biomed Res Int. 2015 Oct 4;2015:163564).
Regarding claim 16, Zhang teaches administering an AAV9 vector comprising a transgene encoding CILP-1 to a mouse model created through Transverse Aortic Constriction (TAC) to demonstrate CILP-1 alleviation of ventricular remodeling and dysfunction (p. 138, 2nd column). Zhang further teaches that C-CILP-1 (a fragment) and full length CILP produced inhibitory effects on TGF-β1 (p. 138, last paragraph; p. 143, 1st paragraph “TGF-β1-induced Smad3 phosphorylation was attenuated by the conditioned medium containing full-, N-, or C-CILP-1 (Fig. 5A)”). Therefore, CILP-1 has a natural mechanism to modulate/inhibit the TGF-β pathway.
However, Zhang does not teach that it is administered to a patient in need thereof who has genetic dilated cardiomyopathies.
Zhou teaches dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and mutations in the protein Titin (TTN) causing truncations are the leading genetic cause of DCM in human patients (p. 1, 1st paragraph-3rd paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to administer CILP-1 in an AAV9 vector as taught by Zhou to a subject with genetic dilated cardiomyopathy as taught by Zhou with a reasonable expectation of success. An artisan would be motivated to do so, as Zhang teaches CILP-1 attenuates ventricular remodeling and dysfunction, a symptom of the genetic dilated cardiomyopathy as taught by Zhou.
Regarding claim 30, the combination of Zhang and Zhou make obvious the method of claim 16. Moreover, Zhang teaches the AAV9 vector encoding a CILP-1 transgene for gene therapy (p. 138, 1st column).
Regarding claims 32-33, the combination of Zhang and Zhou make obvious the method of claim 16. Moreover, Zhou teaches a mouse model with a mutation in titin which is associated with genetic cardiomyopathy (p. 1, 3rd paragraph).
Regarding claim 34, the combination of Zhang and Zhou make obvious the method of claim 16. The specification discloses dosages within the working examples of 1011 vg/mouse equivalent to 1013 vg/kg in a 20 g mouse administered intravenously (para. 0233). Zhang teaches in their online Supplement that 5 x 1011 viral particles are administered to the mouse model (p. 3, 1st paragraph). As the viral particles are purified prior to administration, it is interpreted that these are equivalent to the CLIP-1 vg.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date
Claims 25 and 26 remain rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Journal of Molecular and Cellular Cardiology Volume 116, March 2018, Pages 135-144) in view of Zhou (Biomed Res Int. 2015 Oct 4;2015:163564) as applied to claim 16 above, and in further view of Heckmann (Gene Therapy volume 23, pages 673–679 (2016)).
As discussed above and incorporated here in its entirety, the combined teachings of Zhang and Zhou make obvious a method of administering a AAV9 vector encoding CILP-1 to a patient having genetic dilated cardiomyopathy.
However, regarding claims 25 and 26, Zhang and Zhou do not teach a specific cardiac promoter such as human cardiac troponin T promoter within the vector.
Heckmann teaches human troponin T promoters are utilized for cardiac specific expression (p. 676, 2nd column). Moreover, Heckmann discusses a separate AAV9/troponin T promoter approach in a murine model of young mice which enables a higher transduction efficiency and could potentially prevent progressive cardiac damage during adolescence (p. 677, 1st column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to modify the AAV9 vector taught by Zhang to a subject with genetic dilated cardiomyopathy to comprise a human troponin T promoter as taught by Heckmann with a reasonable expectation of success. An artisan would be motivated to do so, as Heckmann demonstrates that the utilization of AAV9 and troponin T promoters are known in the art for cardiac specific expression of genes.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date
Claims 31 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Journal of Molecular and Cellular Cardiology Volume 116, March 2018, Pages 135-144) in view of Zhou (Biomed Res Int. 2015 Oct 4;2015:163564) as applied to claims 16 and 20 above, and in further view of Duan (Molecular Therapy Vol. 26 No 10 October 2018) and Choi (Current Gene Therapy, 2005, 5, 299-310).
As discussed above and incorporated here in its entirety, the combined teachings of Zhang and Zhou make obvious a method of administering a AAV9 vector encoding CILP-1 to a patient having genetic dilated cardiomyopathy.
However, regarding claim 31, Zhang and Zhou do not teach that the capsid proteins are derived from the AAV9.rh74 serotype.
Duan teaches that clinical trials utilize AAV9 serotypes and AAVrh74 serotypes for gene therapy of Duchene Muscular Dystrophy (Table 5).
Choi teaches in recent years, significant efforts have been made on studying and engineering adeno-associated virus (AAV) capsid, in order to increase efficiency in targeting specific cell types that are non-permissive to wild type (wt) viruses and to improve efficacy in infecting only the cell type of interest (Abstract). Moreover, Hybrid serotypes of AAV have been shown to have tremendous potential for efficient gene delivery and for understanding AAV biology in the past (p. 307, 2nd column).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to substitute the AAV9 capsid of the vector taught by Zhang to a hybrid capsid serotype of AAV9.rh as taught by Duan and Choi with a reasonable expectation of success. An artisan would be motivated to do so, as Duan and Choi demonstrate that AAV9 and AAVrh74 serotypes are both utilized to treat Duchene muscular dystrophy and Choi provides motivation to combine the two into a hybrid AAV in order to improve efficacy in infecting only one cell type.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments and amendments filed 06/29/2026 regarding 103 rejections,
Applicant’s arguments and amendments filed 06/29/2026 have been considered however, they are not persuasive.
Applicant argues that Zhang cannot teach on DCM models when Zhang utilizes TAC models. TAC models have a different mechanism and pathway utilized than that of the DCM diseases. Therefore, Applicant states that the rejection is based on impermissible hindsight. Applicant further argues that Zhou does not cure the deficiencies of Zhang and merely discusses the genetic cause of DCM and therefore, even if combined, there would not be a reasonable expectation of success.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Zhang provides teachings for administering CILP-1 in an AAV9 vector to a mouse model which has TAC to demonstrate CILP-1 alleviation of ventricular remodeling and dysfunction (p. 138, 2nd column). Zhang further teaches that C-CILP-1 (a fragment) and full length CILP produced inhibitory effects on TGF-β1 (p. 138, last paragraph; p. 143, 1st paragraph “TGF-β1-induced Smad3 phosphorylation was attenuated by the conditioned medium containing full-, N-, or C-CILP-1 (Fig. 5A)”). Therefore, CILP-1 has a natural mechanism to modulate/inhibit the TGF-β pathway. In order to demonstrate teaching and motivation to administer the CILP-1 to a subject with DCM, Zhou is utilized. Zhou teaches dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and mutations in the protein Titin (TTN) causing truncations are the leading genetic cause of DCM in human patients (p. 1, 1st paragraph-3rd paragraph). As Zhang demonstrates that CILP-1 attenuates ventricular remodeling and disfunction, an artisan would have been motivated to administer the vector to a subject with DCM as left ventricular dilation is a symptom of DCM. Therefore, an artisan would have been alleviating a symptom of DCM.
New objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 24 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 24 recites “the method according to claim 16, wherein the transgene encodes a CILP-1, DKK3, SRFP2, CCN5/WISP2 protein or a variant thereof comprising a sequence selected from the group consisting of the sequences SEQ ID NO: 2, 4, 6 and 8 and the sequences having at least 85% identity with any one of said sequences.” The species election previously set forth selects SEQ ID NO: 2 which encodes for CLIP-1.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
Applicant’s specification only discloses SEQ ID NO:2 (CLIP-1) (para. 00051) with no other variants.
Claim 24 recites wherein the transgene has at least 85% sequence identity to SEQ ID NO: 2.
SEQ ID NO: 2 is 1184 AA long.
Thus, the claims reasonably encompass as many as 177 amino acid substitutions, insertions, or deletions.
(20)177 = is about 2x10230 possible variants of SEQ ID NO:2 having at least 85% sequence identity to SEQ ID NO: 2.
Thus, it is immediately apparent to the ordinary artisan that the instant claims are vastly broader in scope to Applicant’s actual invention, SEQ ID NO: 2, for encompassing an enormously vast genus of about 2x10230 structurally and functionally undisclosed variants of SEQ ID NO:2 that are to have the functional property of reducing fibrosis through expression of CLIP-1.
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”).
Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)
The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 “merely by clearly describing one embodiment of the thing claimed.” LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005).
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are “representative of the full variety or scope of the genus,” or by the establishment of “a reasonable structure-function correlation.” Such correlations may be established “by the inventor as described in the specification,” or they may be “known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014)
Applicant’s specification fails to disclose a reduction to practice modifying and/or deleting 5, 10, 15, 20, 25, 50, 100, or as many as 177 amino acids of SEQ ID NO:2, thereby generating an enormously vast genus of about 2x10230 variants of SEQ ID NO: 2 that are to have the same functional property.
Rather, Applicant’s working example(s) are directed to the use of a nucleotide sequence that is 100% identical to SEQ ID NO: 2.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 24 is newly rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Journal of Molecular and Cellular Cardiology Volume 116, March 2018, Pages 135-144) in view of Zhou (Biomed Res Int. 2015 Oct 4;2015:163564) as applied to claim 16 above, and in further view of Ikegawa (JP2006223167).
As discussed above and incorporated here in its entirety, the combined teachings of Zhang and Zhou make obvious a method of administering a AAV9 vector encoding CILP-1 to a patient having genetic dilated cardiomyopathy.
However, these references do not teach that the CILP-1 utilized is 85% or more identical to SEQ ID NO: 2.
As shown in the figure below from the Rag search, Ikegawa discloses a SEQ ID NO: 1 which encodes for CILP-1 and has a 100% identity to the present invention’s SEQ ID NO: 2.
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It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize SEQ ID NO: 1 from Igekawa in the method of Zhang to substitute for the full length CILP-1 in the AAV9 vectors with a reasonable expectation of success. An artisan would have been motivated to do so as SEQ ID NO: 1 of Igekawa is a known equivalent sequence which encodes for the same protein as the CILP of Zhang.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16, 24-26 and 30-34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 16 and by dependence, claims 24-26 and 30-34 are vague and indefinite in the recitation of “…capable of…” , since this phrase refers to a latent ability, and it is unknown whether the ability is expressed or observed in the invention.
Note, it has been held that the recitation that an element is “capable of” performing a function is not a positive limitation, but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchinson, 69 USPQ 138.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA CONNORS whose telephone number is (571)272-7010. The examiner can normally be reached Monday - Friday (9AM-5PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MARIA LEAVITT can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEXANDRA F CONNORS/ Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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