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 .
Claim Status
Claims 1-21 are currently pending in this application.
Election/Restrictions
Election was made with traverse of Group I, claims 1-4, and without traverse the species of SEQ ID NO: 12 or 18, position 587, polypeptide and retinal cell disease in the reply filed on April 24, 2026. Because SEQ ID NO: 12 and 18 were elected as species in the alternative, the election is interpreted as electing the first mentioned SEQ ID NO: 12.
The traversal is on the grounds that the claims have been amended such that there would not be a serious burden. This is not found persuasive because burden is immaterial to a finding of lack of unity of invention pursuant to Rule 13.1 (see MPEP 1893.03(d)). In view of Schaffer disclosing an AAV capsid protein comprising an insertion of SEQ ID NO: 12 or 18 ([0090], [00116], [0180]), the restriction is made final. Upon further consideration, the restriction has been modified to group claims 11-13 into Group I and completely withdraw Group III. Thus, claims 5-10 and 14-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected subject matter, there being no allowable generic or linking claim. Claims 1-4 and 11-13 as a unified group have been considered on the merits.
Objections to the Disclosure
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiencies – This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on FIG. 1 and 2 of the Drawings but are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Regarding the Drawings
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claim 4 recites a list of SEQ ID NOs separated by commas, which as opposed to being drafted with standard Markush language, uses nonstandard language which is suggested to be rewritten with an ‘and’ or ‘or’ between the list two items in the list. Appropriate correction is required.
Claim Interpretation
In claim 1, the term “polypeptide” is interpreted as being any length as defined in the specification (see [0154]).
In claim 2, the term “VP1” is interpreted as referring to a gene (Cap) or ORF (Cap ORF), whether naturally occurring or synthetic (see instant [0131]-[0132], [0140], [0147]).
In claim 3, the term “mutation” includes substitutions, deletions and/or additions, and thus the term point mutation is interpreted as any one of a single substitution or deletion so long as the residue present has changed relative to the AAV2 capsid protein set forth in SEQ ID NO: 1 or a another AAV serotype capsid protein having correspondence thereto to the residue recited at the recited position, such as determined by a sequence alignment.
In claim 4, the protein according to claim 1 having the amino acid sequence is interpreted as “consisting of,” and similarly, the protein according to claim 1 having “at least 90% or 95% sequence identity” to any one of “SEQ ID NOs: 4, 9, 23” is interpreted as meaning the protein over its full length has at least 90% sequence identity (see [0146]).
In claim 12, the term “vector” is interpreted as used in the specification as including a polynucleotide (e.g., capable of transforming a host cell) or phage or virion particle comprising such a polynucleotide (e.g., plasmid or viral genome) (see [0137], [0143], [0145], [0156]).
Claim Rejections - 35 USC § 112(a), Written Description
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 1-4 and 11-13 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 for failing to particularly point out and distinctly claim the subject matter. 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.
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 applicant’s 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 making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. The invention of claim 1 or 11 is an AAV capsid protein comprising an insert of instant SEQ ID NO: 12 or any polynucleotide encoding the aforementioned.
Inserted Polypeptide (relative to parental)
Claim 1 is broad in that said insert polypeptide merely “comprises” an expressly recited sequence while the term “polypeptide” can be of any length without limit as defined in the specification (see [0154]).
The preamble of “adeno-associated virus (AAV) capsid protein” implies the limitation that the protein must somehow function as an AAV capsid protein (e.g., a parental AAV capsid protein) despite variations therefrom. The instant specification only describes in detail inserts wherein the size of the insert is no larger than 11 amino acid residues ([0011]). However it must be emphasized that the scope the claims encompasses insertions with no limitation in sequence nor length/size so long as the insertion comprises at least one recited sequence so long as the AAV capsid protein possesses at least one known AAV capsid protein functionality.
The instant application describes putative examples of species of such proteins related to a parental protein wherein the insertions have a length of 7-10 amino acids inserted at position 588 (VP1 AAV2) or 589 (VP1 AAV9) and verified to retain a partial (e.g., minimal) AAV capsid protein activity of a known AAV capsid protein (e.g., a VP1 capsid protein function) (Table 1, Example 2; SEQ ID NO: 4, 9 and 23).
Regardless, the instant specification describes prophetic embodiments comprising longer inserts and differing insert positions, with no upper limit. Because it is too unpredictable for a functional AAV capsid protein (VP1, VP2, or VP3 capsid protein) to tolerate insertions of unlimited size and at any position.
The prior art teaches that insertions of peptides as small as 6 and/or 8-10 amino acids into AAV2 capsid proteins at various positions can destroy protein function (Wu et al., J Virol 74: 8635-47 (2000) at Table 2; Fig. 3). The prior art teaches that insertions of peptides having 6 and/or 8-10 amino acids (HIS, AU, FLAG, HA, or Ser) into AAV2 capsid proteins at various positions inhibited virion production or produced defective virions (e.g., at position 10, 24, 39, 76, 84, 150, 178, 203, 328, 454, 522, 526, 547, 553, 562, 638, 664, or 682) (Wu et al. (2000) at Fig. 1, Table 1). For example, these insertions resulted in “noninfectious” virions having an infectivity 5-logs lower compared to wild-type due to being unable to make capsids or failing to make stable capsids (class 4b) or being defective in a host cell binding, internalization, and/or uncoating step(s) (class 4a or 4d) (Wu at Table 2; Fig. 3). In another example, while some prior art teaches position 587 the capsid proteins of AAV2 are permissive for insertions, other prior art shows unpredictability at just this single site with NLS insertions causing a six-fold reduction in capsid assembly, ten-fold drop in packaging efficiency, loss of host cell binding, and a drastic reductions in infectivity (Douar et al. Virology 309: 203-9 (2003); at Abstract; Table 1; Fig. 2-3C; pg. 206, left col., last para., to right col., 2nd para.).
Thus not any position in an AAV capsid protein can tolerate a peptide insertion and it is not predictable which positions will or will not tolerate a given peptide sequence as an insert. As the prior art does not teach any predictable pattern for permissive insertion sites, these aspects must be described to a reasonable extent so that one of the ordinary skills in the art would recognize that Applicant was in possession of these insertion sites at the effective filing date of the claimed invention. Furthermore, as the prior art teaches away specifically from positions 39, 150, 454, and 587, more convincing evidence may be required to sufficiently describe to one of skill in the art that Applicant was in possession of these specific insertion sites in view of the prior art.
Thus, the genus of insertions comprising any sequence with no upper size limit is not sufficiently described by a representative number of species. Protein function is too unpredictable in general and in particular the functioning of AAV capsid protein in particular is too easily perturbed as taught by the art. Therefore in the instant case, empirical evidence is needed to show possession for inserts larger than about 11 amino acid residues or at any insertion position as the skilled artisan cannot envision the full scope of claim 1 predictably providing AAV capsid protein functionality.
As explained by the Federal Circuit, “(1) examples are not necessary to support the adequacy of a written description; (2) the written description standard may be met … even where actual reduction to practice of an invention is absent; and (3) there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure. However, the claimed invention itself must be adequately described in the written disclosure and/or the drawings, such as using identifying structural characteristics (e.g., structural motifs or consensus sequences) or combinations of characteristics (e.g., a motif and overall hydrophobicity, polarity or charged side chains or a structural motif conferring an importin receptor binding activity) (see MPEP 2163).
Conclusion
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116). As discussed above, the skilled artisan cannot envision the structure(s) of the insertions regarding both sequence and length which allow for preservation of at least partial AAV capsid protein function based on the information provided in the instant application, and therefore conception is not achieved until reduction to practice has occurred, 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 potential and generic ways of modifying an AAV capsid protein via insertion of undefined amino acid sequences at virtually any location. The compound 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.
Therefore, the claims contain 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 inventors, at the time the application was filed, had possession of the full scope of the invention as claimed.
Claim Rejections - 35 USC § 112(b)
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 1-3 and 12-13 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 the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 and 2 each recites an inserted polypeptide relative to a “parental” AAV capsid protein, which is indefinite for being relative to the term “parental” such protein unanchored to any reference or consensus protein (e.g., a sequence, protein family, or species/virus specific subtype thereof) as neither the claim nor the specification provides a standard or means for determining a boundary for an insert in a “parental” protein to inform the skilled artisan of the metes and bounds of this limitation. Claims 2-3 and 11-13 are included in this rejection for depending from indefinite claim 1.
Claim 2 recites the term “the VP1 encoded amino acid sequence of the parental AAV2 capsid protein,” which both lack sufficient antecedent basis in the claim or in claim 1.
Claim 2 and 3 each recites the phrase “or at a corresponding position of other parental AAV serotype capsid proteins,” which is indefinite for using the relative term “a corresponding position” of any other parental AAV serotype capsid protein that is unanchored to any reference or consensus protein (e.g., a sequence, species, virus type, etc.) as neither the claim nor the specification provides a standard or means for determining a boundary for a corresponding position in any other “parental” protein regardless of serotype to inform the skilled artisan of the metes and bounds of this limitation.
Claim 12 recites a vector comprising the “isolated” polynucleotide, which is incoherent and unclear as to how a polynucleotide is simultaneously both isolated and in the presence of a vector according to the ordinary meaning of the term “isolated.” Perhaps the vector is “isolated” instead. Claim 13 is included in this rejection for depending from indefinite claim 12 and presents similar issues for the such a vector.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 11-13 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Schaffer (US 20140294771 A1).
The claims are interpreted as set forth in a previous section.
Regarding claims 1 and 2, Schaffer discloses an adeno-associated virus (AAV) capsid protein (VP1) comprising SEQ ID NO: 12 inserted after position 588 ([0090], [00116], [0180], as described in “Formula IV”; [0103]). In the formula, where X1X2X3X4X5X6X7 is consensus sequence wherein X1 is selected from Leu, Asn, Arg, Ala, Ser, and Lys; X2 is selected from Gly, Glu, Ala, Val, Thr, and Asp; X3 is selected from Glu, Thr, Gly, Asp, or Pro; X4 is selected from Thr, Ile, Gly, Lys, Asp, and Gln; X5 is selected from Thr, Ser, Val, and Ala; X6 is from Arg, Val, Lys, Pro, Thr, and Asn; and X7 is selected from Pro, Gly, Phe, Asn, and Arg, this consensus discloses instant SEQ ID NO: 12.
Regarding claims 11-13, Schaffer discloses an isolated polynucleotide, AAV virion, or host cell comprising a polynucleotide encoding said protein ([0168], [0185]-[0187]).
Thus, Schaffer anticipates the claimed invention.
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.
Claims 1-3 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffer in view of AAS99264 (GenBank Accession No. AAS99264 (2004)).
As set forth fully above, Schaffer anticipates claims 1-2 and 10-13, and thus, renders obvious the subject matter of claims 1-2 and 10-13.
Regarding claim 3, Schaffer teaches wherein the VP1 capsid protein comprises an amino acid sequence having zero or 1 to about 25 amino acid mutations outside the insertion compared to a parental capsid protein ([0094]), such as AAS99264 ([0074]) which comprises 34A as shown below.
98.7% identity in 746 residues overlap; Score: 3934.0; Gap frequency: 1.3%
Sequence9 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD
AAS99264 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD
************************************************************
Sequence9 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ
AAS99264 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ
************************************************************
Sequence9 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE
AAS99264 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE
************************************************************
Sequence9 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI
AAS99264 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI
************************************************************
Sequence9 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR
AAS99264 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR
************************************************************
Sequence9 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH
AAS99264 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH
************************************************************
Sequence9 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV
AAS99264 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV
************************************************************
Sequence9 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP
AAS99264 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP
************************************************************
Sequence9 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS
AAS99264 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS
************************************************************
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to create a VP1 capsid protein insert variant comprising the point mutation 34A relative to a parental protein. One of ordinary skill in the art would be motivated to use any equivalent capsid protein backbone expressly taught by Schaffer ([0074]), such as 34A as taught by AAS99264. Furthermore, there is no evidence that 34A has any functional difference.
Claims 1-2, 4, and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Schaffer in view of Chalberg (US 20180066022 A1).
As set forth fully above, Schaffer anticipates claims 1-2 and 10-13, and thus, renders obvious the subject matter of claims 1-2 and 10-13.
Regarding claim 4, Schaffer does not expressly teach wherein the AAV capsid protein comprises a sequence having at least 90% or 95% sequence identity to SEQ ID NO: 4, 9, or 23.
However Chalberg teaches an AAV VP1 capsid protein (SEQ ID NO: 19) having over 95% sequence identity to SEQ ID NO: 4 or 23 as shown below.
Query Match 99.9%; Score 4039; Length 745;
Best Local Similarity 99.7%;
Matches 743; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDTLSEGIRQWWKLKPGPPPPKPAERHKDDSRGLVLPGYKYLGPFNGLD 60
Qy 61 KGEPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRVLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDAD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRVLEPLGLVEEPVKTAPGKKRPVEHSPVEPDSSSGTGKAGQQPARKRLNFGQTGDAD 180
Qy 181 SVPDPQPLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPLGQPPAAPSGLGTNTMATGSGAPMADNNEGADGVGNSSGNWHCDSTWMGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISSQSGASNDNHYFGYSTPWGYFDFNRFHCHFSPRDWQRLI 300
Qy 301 NNNWGFRPKRLNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NNNWGFRPKRLNFKLFNIQVKEVTQNDGTTTIANNLTSTVQVFTDSEYQLPYVLGSAHQG 360
Qy 361 CLPPFPADVFMVPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPF 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CLPPFPADVFMVPQYGYLTLNNGSQAVGRSSFYCLEYFPSQMLRTGNNFTFSYTFEDVPF 420
Qy 421 HSSYAHSQSLDRLMNPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 HSSYAHSQSLDRLMNPLIDQYLYYLSRTNTPSGTTTQSRLQFSQAGASDIRDQSRNWLPG 480
Qy 481 PCYRQQRVSKTSADNNNSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 PCYRQQRVSKTSADNNNSEYSWTGATKYHLNGRDSLVNPGPAMASHKDDEEKFFPQSGVL 540
Qy 541 IFGKQGSEKTNVDIEKVMITDEEEIRTTNPVATEQYGSVSTNLQRGNLALGDTTRPARQA 600
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Db 541 IFGKQGSEKTNVDIEKVMITDEEEIRTTNPVATEQYGSVSTNLQRGNLALGETTRPARQA 600
Qy 601 ATADVNTQGVLPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKN 660
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Db 601 ATADVNTQGVLPGMVWQDRDVYLQGPIWAKIPHTDGHFHPSPLMGGFGLKHPPPQILIKN 660
Qy 661 TPVPANPSTTFSAAKFASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSINV 720
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Db 661 TPVPANPSTTFSAAKFASFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYNKSVNV 720
Qy 721 DFTVDTNGVYSEPRPIGTRYLTRNL 745
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Db 721 DFTVDTNGVYSEPRPIGTRYLTRNL 745
Although Chalberg does not teach wherein the AAV capsid protein comprises the insert comprising instant SEQ ID NO: 12, instead teaching LGETTRP, Chalberg does provide a variant AAV VP1 backbone for inserting a 5-11 amino acid peptide insert into the GH loop at position at position 590 or a protein 85%, 90%, 95% or 97& or more to SEQ ID NO: 16 (7m8) shown above ([0081]). Further, Schaffer teaches in the peptide insert in an adeno-associated virus (AAV) capsid protein (VP1) consisting of SEQ ID NO: 12 (as described in “Formula IV” and set forth above in the 102 section; [0090], [00116], [0180], [0103]). Schaffer teaches at position X3 of the insert the amino is selected from either Glu or Asp while Chalberg teaches Glu.
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to create a VP1 capsid protein insert consisting of instant SEQ ID NO: 12 with X3 as ASP in the parental protein SEQ ID NO: 16 as taught by Chalberg. One of ordinary skill in the art would be motivated to use any equivalent capsid protein backbone expressly taught in the prior art. When there is a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options of the prior art within her technical grasp to reach a workable configuration (see MPEP 2144.05 (II)). Furthermore, there is no evidence that position E592D in this context has any functional difference. Thus, the claimed invention as a whole is prima facie obvious before the effective filing date in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/ERIC J ROGERS/
Examiner, Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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