DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to a claim set filed 8/4/2026.
Claims 1-20 are pending.
This application is a continuation of U.S. Patent Application No. 17/707,944, filed March 29, 2022, which is a continuation of U.S. Patent Application No. 17/614,327, which is a National Phase Application under 35 U.S.C. § 371 of PCT/US2021/042812, filed July 22, 2021 which claims the benefit of and priority to U.S. Provisional Patent Application No. 63/055,265, filed on July 22, 2020, U.S. Provisional Patent Application No. 63/107,394, filed on October 29, 2020, and U.S. Provisional Patent Application No. 63/183,038, filed on May 2, 2021.
Information Disclosure Statement
An Information Disclosure Statement filed 8/4/2026 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action. References initialed but crossed off of the Form 1449 have been considered.
Response to Amendments
Applicants’ amendment is sufficient to overcome the objections to the specification. Applicants’ amendment and arguments are sufficient to overcome the objections to the claims. Applicants’ arguments in combination with the terminal disclaimer filed 8/4/2026 is sufficient to overcome the rejections under non-statutory double patenting.
The terminal disclaimers filed on 8/4/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on U.S. Patent 12,618,082 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Objections
Claim 3 is objected to because of the following informalities: claim 3 recites “in variable region (VR-VIII)”. The parenthesis appears to designate the region of insertion as an abbreviation. However, these are specific variable regions and reference should be to –the variable regions VR-VIII--. This is a new objection. Appropriate correction is required.
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 1, 2, 4, 9 and 12-20 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims were incorrectly identified in the previous office action and hence this rejection is restated and the office action is non-final.
The instant claims are drawn to an AAV capsid protein for targeting muscle cells wherein the targeting moiety comprises the amino acid sequence of SEQ ID NO:32. This sequence is 1-ENRRGDFNNT-10. It is an RGD containing motif. The scope of the invention is broad in that the AAV is any and the insertion sites embrace a large number of such sites (Claims 1, 2, 4, 9, and 12-20). To this end, the specification is limited to demonstration of inserts into AAV9 at the VR-VIII loop. The examples are limited to insert sites with AAV9 after amino acid 588 of the VP protein.
First, each variant included a random 7-mer peptide inserted between amino acids 588 and 589 in the hypervariable region VIII of the AA V9 capsid, a design that ensures exposure of the variable peptide sequence on the capsid surface ((DiMattia et al., 2012)
But, analysis was made for inclusion of surrounding sites based in AAV9.
[0682] Based on a predicted structure for the MyoAAV hypervariable region VIII surface loop, amino acids in positions 586, 587, and 588 upstream and positions 592, 593, 594, and 595 downstream of the RGD motif were identified as likely to be located in the surface loop of MyoAAV (FIG. 19A). A diverse library of capsids were generated, each with the RGD motif fixed at positions 589, 590, and 591 and varying amino acids in the above-mentioned flanking positions (FIG. 19B).
This is shown in the figure (19A and 19B).
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As shown, applicants have inserted the 7 mer into the loop domain such that the sequences on the 5’ end and the 3’ end of the RGD insert replace those of the loop. This is a specific structure reflected in claim 7 for AAV9 and claim 11 for AAVrh7.4.
The following issues with lack of description have been identified. Applicants have not identified either in the art or the disclosure that any site in the capsid that can incorporate the targeting moiety such that the capsid is “effective to target a muscle cell”. This would require structural integrity to meet the function. There is no dispute that the loop domain has been shown to keep structural integrity of a capsid and provide retargeting. But, the step of replacing amino acids is an extrapolation of this concept without description in the specification.
Thus, considering the claims, applicants claim a large breadth of AAV and insertion sites but do not describe the full breadth that can mediate muscle transduction. The court and the Board have repeatedly held (Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,18 USPQ2d 1016 (CA FC, 1991); Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993); Fiddes v. Baird, 30 USPQ2d 1481 (BPAI 1993) and Regents of the Univ. Calif. v. Eli Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)) that an adequate written description of a compound requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the compound itself. It is not sufficient to define a product solely by its principal biological property, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any peptide with muscle cell tropism with that biological property. Naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. When one is unable to envision the detailed constitution of a complex chemical compound having a particular function, such as a biomolecule so as to distinguish it from other materials, as well as a method for obtaining it, conception has not been achieved until reduction to practice has occurred, i.e., until after the molecule has been isolated. This is complicated as insertion sites are limited due to the impact of the insertion on the structural integrity of the capsid. As well, the secondary structure does not naturally allow for any site within the capsid to be available. Claiming any AAV in any site and even AAVrh74 in any site or amino acids 587-591 furthermore with deletions of 588-590 is nothing more than a wish list to possess AAV that achieve a result without defining what means will do so is not in compliance with the description requirement. Rather, it is an attempt to preempt the future before it has arrived. Also, where a claim purports to cover all capsid insertion sites and the specification discloses but a single known to do work in the desired fashion, the situation is analogous to a single means claim and does not meet the enablement requirement under para. 1 ' of§112.
As set forth above, the specification does not provide adequate guidance of the structural requirements and hence the claims also lack Written Description such that a person of skill in the art would recognize that they were in possession of the genus of methods and resulting microbeads made according to the more specific embodiments in the disclosure. The MPEP teaches, “However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative. Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971). (see MPEP 2164.08(b)). Given the large size and diversity of biocompatible polymers, curing methods and means to that are related by 98% to SEQ ID NO: and the inability to determine which will also have the essential element, it is concluded that the invention must be empirically determined. In an unpredictable art, the disclosure of no species would not represent to the skilled artisan a representative number of species sufficient to show applicants were in possession of claimed genus.
It is newly noted, claim 4 recites that the modified AAV capsid polypeptide is an AAV9 capsid polypeptide. This reads on a large genus of polypeptides in that first, the claims refer to “an” AAV9 capsid polypeptide. This reads on partial sequences. Even should it not be intended to read on partial sequences and should read on the whole of AAV9 capsid, the sequence is wild type and cannot be also modified.
Response to Arguments
Applicants argue that the intent of the rejection was enablement. However, this is not the case, the claims recite a broad genus of structures by functional properties that are not reasonably supported by the disclosure. The structure of the capsids is one that can effectively “target a muscle cell” and comprise the amino acid of SEQ ID NO:32. This is a function inadequately supported by the disclosure which only teaches, and is not further elucidated by the art, the n-mer of SEQ ID NO;32 inserted into the VR-VIII domain. The claims further recite that amino acids are replaced by those of the n-mer. However, the disclosure does not teach any other structure than that of AAV9. As well, the art does not complement this claim. As applicants state, “Written description is assessed from the perspective of a person of ordinary skill in the art ("PHOSITA") as of the priority date” and there is no evidence that the full scope of claims 1, 2, 4, 9 and 12-20 is described in the specification or the art.
Applicants argue that the disclosure names serotypes and links the structure to other named serotypes and indicates that the first 1-4 amino acids of the n-mer can replace the 1-4 amino acids of the polypeptide. As to these teachings, the issue is two-fold. First, it is aptly noted that the Federal Circuit has decided that a generic statement that defines a genus of substances by only their functional activity, i.e., the ability to specifically bind a polypeptide and inhibit its function, does not provide an adequate written description of the genus. See the Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Here, simply indicating that the n-mer can be inserted into the capsid is not sufficient to satisfy the written description in order to satisfy the written description requirement. Secondly, applicants invoke language in the claims regarding replacing amino acids of rh74 and do not provide the actual description thereof. Hence, applicants have not described this species claimed.
As to the relationship with Amgen, applicants argue that the molecules were known. However, applicants cite to any insertion and replacement of any amino caid in rh74 and these are neither known nor taught in the disclosure. Applicants claims are nothing more than a wish to know the identity of any capsid with the claimed biological properties.
Conclusion
SEQ ID NO:32 is free of the prior art outside of applicants’ own application history.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached on 8 am - 5 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/
Primary Examiner, Art Unit 1633
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