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 .
Election/Restrictions
Applicant’s election of Group I, claims 73-89 in the reply filed on 5/21/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 90-98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/21/2026.
Claims 73-89 are examined in the instant application.
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.
Claims 73-89 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 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.
When the claims are analyzed in light of the specification, the instant invention encompasses a capsid polypeptide comprising any sequence having at least 95% sequence identity to SEQ ID NO: 7 (AAV9 wild-type VP1) or any portion of VP2 or VP3 and comprising nine mutations set forth in (a)-(i) of claim 73.
Regarding function, the claims recite that a nucleic acid will encode a capsid polypeptide and the structural limitation of the claims is that the encoded polypeptide will form and function as a viral capsid.
However, the specification provides no description of any amino acid sequence, other than for an amino acid sequence which is 100% identical to SEQ ID NO: 7 and comprises the mutations set forth in (a)-(i) in claim 73, that would indicate possession at the time of filing for an amino acid sequence that forms and functions as a viral capsid. 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 structure. In the instant case, only an amino acid sequence which is 100% identical to SEQ ID NO: 7 and comprises the mutations set forth in (a)-(i) in claim 73 and forms a viral capsid, is sufficiently described to indicate possession of the claimed capsid polypeptide and nucleic acid encoding said capsid polypeptide. The specification does not provide any disclosure as to what the complete structure would be of any other amino acid sequence other than the one disclosed in the specification that would form a viral capsid and function as claimed. There is no general knowledge in the art about regarding viral capsids and comprising the nine mutations set forth in (a)-(i) in claim 73 to suggest that general similarity of structure confers the activity.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only characteristic described, is that when SEQ ID NO: 7 comprises the nine mutations set forth in (a)-(i) of claim 73, a viral capsid is formed. The specification does not teach any other identifying characteristics such as domains relating to function/activity or any other related sequences that would guide the artisan to contemplate other sequences other than one that is 100% identical to SEQ ID NO: 7 and comprises the nine mutations set forth in (a)-(i) of claim 73.
The specification teaches that the combination of nine mutations were observed after performing high-throughput AAV9 screening in a variety of tissues (see Example 2 starting on pg. 219). Specifically, the specification teaches:
“AAV capsid variant V1 showed an increase in biodistribution to skeletal and cardiac
muscle tissues and a decrease in biodistribution to the liver relative to biodistribution associated with wildtype AAV9 in these tissues (Table 7B). AAV capsid variant V1 also displayed increased transduction in skeletal and cardiac muscle tissues, relative to transduction associated with wildtype AAV9” (parag. 313 lines 1-4); and
“The results show that many variants containing one or more of mutations of V1 target liver less than WT AAV9, target heart (e.g., primate heart or murine heart) more than WT AAV9, target muscle (e.g., primate muscle or murine muscle) more than WT AAV9, and/or target spleen (e.g., primate spleen or murine spleen) less than WT AAV9 with respect to biodistribution and/or transduction. Some evaluated mutations, e.g., H584K, Q588Y, and/or W595A are important for in vivo muscle targeting. The results further show that some evaluated mutations, e.g., Q579T, are important for liver detargeting. The results further show that some evaluated mutations, e.g., R550H, S576A, and/or I601V, are important for capsid productivity. The results further suggest that some evaluated mutations, e.g., V596L and/or N598S, are important for in vitro muscle targeting of relevant human muscle cell lines (FIGS. 2A-20, 3A-30, 4A-40, and 5A-5O). Furthermore, for some evaluated properties, variant capsids with up to an edit distance of 2, 3, 4, 5, 6, 7, or 8 amino acids showed comparable or improved function relative to WT AAV9 (FIGS. 6A-60).” (parag. 315).
However, while the specification contemplates and the claims encompass an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 7 or any portion of VP2 or VP3, the specification does not provide any support for any sequence other an amino acid sequence which is 100% identical to SEQ ID NO: 7 and comprises the mutations set forth in (a)-(i) in claim 73.
This is significant since the specification does not teach what the structure of a modified capsid, comprising nine mutations in any portion of VP2 or VP3 and would result in forming a capsid as required by the claims. SEQ ID NO: 7 is 736, VP2 is 601 and VP3 is 533 amino acids in length. 5% of SEQ ID NO: 7 is 36.8 amino acids, and encompasses deletion of the first ~36 amino acids of SEQ ID NO 7. Further, the claims encompass any portion of VP2 or VP3 that also comprise the nine mutations set forth in (a)-(i). This encompasses a range of amino acids from just 550 to 601, i.e the range of mutations in VP2 or VP3. The specification does not providing a limiting definition for what is encompassed by a portion of VP2 or VP3 and this is significant since the art teaches that mutations in a capsid can prevent the capsid from forming in an AAV and alter the function of an AAV (see Choi et al, 2005, Curr. Gene Ther., Vol. 5(3), pgs. 299-310, specifically pg. 12 parag. 4). Thus the claims encompass “A capsid polypeptide comprising an amino acid sequence having at least a VP3 portion thereof and comprising” the mutations (a)-(i). Since any portion of VP2 or VP3 that comprises the mutation (a)-(i) is encompassed by the claims, the teachings of Choi are particularly applicable since no capsid will be formed by the encoded polypeptide, since the polypeptide will only be 11 amino acids in length.
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of variants of an rAAV that would comprise an insertion of a heterologous peptide anywhere in the GH loop at the time of filing.
Applicants' attention is directed to the decision in Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, which clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed." (See page 1117.) 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).
With the exception of the sequences referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed polynucleotides, and therefore conception is not achieve regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an amino acid sequence which is 100% identical to SEQ ID NO: 7 and comprises the mutations set forth in (a)-(i) in claim 73 meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In conclusion, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that applicant is in possession of the genus of capsid polypeptides thereof as embraced by the claims.
Conclusion
No claims are allowed. The claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
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