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 .
Response
Applicant’s response and claims amendment filed on 08/13/2025 are acknowledged.
Claims 13-14, 16, 19 and 25 are amendment. New claim 34 is added.
Claims 13-19, 25 and 34 are considered.
Claims 20-24 and 26-32 are withdrawn from consideration.
Claim Rejections - 35 USC § 102
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.
Claims 13-15, 17-19 are still rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Gao et al. (J. Virol. 78:6381-6388(2004) potentiated by Li et al. (Cellular & Molecular Biology , 2014, Vol 6 (1): 6-11). Moreover, claims 25 and new claim 34 are also rejected as claims amended as well as new claims necessitated by Applicants’ amendment under 35 U.S.C. 102 (a) (1) as being anticipated by Gao et al. (J. Virol. 78:6381-6388(2004) potentiated by Li et al. (Cellular & Molecular Biology , 2014, Vol 6 (1): 6-11) and Savy et al. (HUMAN GENEW THERAPY METHODS, VOLUMN 28, NUMBER 5, , 2017, PAGES 277-289).
In the response, Applicants amendment claims and submit that the cited reference by Gao et al. do not teach the newly added limitations that Gao et al. do not teach a promoter that is active in insect cells a or the new claim 34 with a intended or a potential function of the nucleic acid construct with same structural characteristics of five mutations of A67E, Q81R, K84D, A85S and R92K refereeing to the SEQ ID NO: 1.
Applicants’ amendment and argument have been respectfully considered; however, they are not persuasive to overcome the rejection with the following reasons:
1). The VP1 protein encoded by the nucleic acid construct of the recombinant AAV viral vector disclosed by Gao comprises the same identical five mutations at the same corresponding amino acid residues. This was presented by the last office action and restated herein:
Please see detail the underlined amin acids at positions A67E, Q81R, K84D, A85S and R92K referenced to the SEQ ID NO: 1
61 KGEPVNEADAAALEHDKAYDXQLXXGDNPYLXYNHADAEFQERLQEDTSFGGNLGRAVFQ 120
||||||||||||||||||||:||::||||||:||||||||||||:|||||||||||||||
GEPVNEADAAALEHDKAYDRQLDSGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
2). Gao et al. also teach using a promoter namely cytomegalovirus-enhanced chicken -actin promoter, which can officially drives heterologous gene expression in Sf6 insect cells as evidenced by Li et al. (Cell Mol. Biol, 2014, 60(1): 6-11).
Moreover, because WT ITRs are symmetrical 145-nucleotide sequences that flank the ends of the single stranded DNA genome of AAV in the native virus, which is a key element of AAV involved in the viral replication and encapsulation of the AAV genome as evidenced by Savy et al. (HUMAN GENEW THERAPY METHODS, VOLUMN 28, NUMBER 5, , 2017, PAGES 277-289). Therefore, while Gao et al. do not explicitly teaches the ITR is contained in the AAV6 viral vector, the vector inherently contains ITR in addition to mutations of A67E, Q81R, K84D, A85S and R92K refereeing to the SEQ ID NO: 1
As described above, the cited reference by Gao et al. still inherently anticipates claims 13-15, 17-19, 25 and 34.
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.
Claims 13-19, 25 and 34 are still rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (J. Virol. 78:6381-6388, 2004) as applied to claims 13-15 and 17-19 above, and further in view of US Patent No. 7,271,002 to Kotin et al.
In the response, Applicants traverse the rejection by asserting there is no motivation to combine using promoter taught by Kotin et al. with the AAV virus vector taught by Gao et al. because there is no expectation of the success based on the case law of KSR.
Applicants’ argument has been respectfully considered, however it is not found persuasive.
The case law about KSR International Co. v. Teleflex Inc.– conclude that Ordinary Innovation is obvious. In KSR, the Supreme Court did not entirely reject the “teaching, suggestion, or motivation” test, but the Court ruled that any teaching, suggestion or motivation does not need to be explicit and courts can take into account the inferences and creative steps that a person of ordinary skill in the art may employ: “A person of ordinary skill is also a person of ordinary creativity, not an automaton.” In order to determine whether there was a reason for one skilled in the art to combine known elements in a manner claimed by the patent, courts must analyze the interrelated teachings of prior art references, the effects of known demands in the marketplace, and the background knowledge possessed by a person of ordinary skill in the art. The Supreme Court stated that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results, and further indicated that any of the following may provide a “reason” for combining these known elements: a need or problem known in the field of endeavor at the time of invention and addressed by the patent; an obvious use of familiar elements beyond their primary purposes; or a design need or market pressure to solve a problem (Morrow et al. The case law about KSR International Co. v. Teleflex Inc.– conclude that Ordinary Innovation is Obvious, published in the internet website: www.fewick.com, 2007, pages 1-2).
Therefore, suggestion or motivation does not need to be explicit and courts can take into account the inferences and creative steps that a person of ordinary skill in the art may employ. “A person of ordinary skill is also a person of ordinary creativity, not an automaton.” Furthermore, the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.
Hence, absence of an unexpected result to the contrary, the claimed invention as a whole is prima facie obvious absence unexpected results.
As it is described clearly above, Gao et al. teach the well know AAV serotype 6, which inherently comprises a nucleic acid sequences encoding the gene of VP1 protein that comprises all same five amino acid mutations at the same amino acid residues of A67E, Q81R, K84D, A85S, and R92K , and are capable of being constructed as a recombinant expression VECTOR as a common science and technical knowledges for any person with an ordinarily skilled in the art to use for expressing a heterologous sequence used for a GENE THERAPY (See Abstract and Materials and Methods, Figures 1-4). While Gao is silence for using special baculoviral vector promoter, this is not exclusively required by the rejected claims.
Kotin et al. teach a method of producing an adeno-associated virus (AAV) in an insect cell comprising (i) providing at least one insect cell-compatible vector, which is a baculovirus inherently comprising a first nucleotide sequence of at least one AAV ITR nucleotide sequence, a second nucleotide sequence containing an open reading frame encoding AAV VP1, VP2, and VP3 capsid proteins, a third nucleotide sequence comprising a Rep52 or a Rep40 coding sequence, and a fourth nucleotide sequence comprising a Rep78 or a Rep68 coding sequence, (ii) introducing the at least one insect cell-compatible vector into an insect cell, and (iii) maintaining the insect cell under conditions such that AAV is produced. Kotin et al. also describes a recombinant AAV made in accordance with the method, insect cell-compatible vectors, i.e. a baculoviral vector , and insect cells comprising nucleotide sequences for production of AAV in an insect cell. For instance, the method of producing an adeno-associated virus (AAV) in an insect cell, comprising: (i) providing at least one insect cell-compatible vector comprising a first nucleotide sequence comprising at least one AAV inverted terminal repeat (ITR) nucleotide sequence, a second nucleotide sequence comprising an open reading frame (ORF) comprising nucleotide sequences encoding AAV VP1, VP2, and VP3 capsid proteins operably linked to at least one expression control sequence for expression in an insect cell, a third nucleotide sequence comprising a Rep52 or a Rep40 coding sequence operably linked to at least one expression control sequence for expression in an insect cell, and a fourth nucleotide sequence comprising a Rep78 or a Rep68 coding sequence operably linked to at least one expression control sequence for expression in an insect cell, wherein said fourth nucleotide sequence comprises an expression control sequence selected from an immediate early 1 gene (IE-1) promoter, a ΔIE-1 promoter, a promoter substantially homologous to the IE-1 promoter, and a promoter substantially homologous to the ΔIE-1 promoter, wherein said at least one vector is a baculoviral vector, a viral vector or a plasmid, (ii) introducing said at least one insect cell-compatible vector into an insect cell, and (iii) maintaining said insect cell under conditions such that AAV is produced, wherein said insect cell is Sf9 (Claim 30).
Therefore, it would have been obvious for a person with an ordinarily skilled in the art to be motivated by the cited reference to use the method taught by Kotin et al. for producing a recombinant AAV vector using the a baculovirus vector to express the VP1 disclosed by Gao et al. to produce a recombinant AAV vector with a reasonable expectation of successful result. Hence, the claimed invention as a whole is prima facie obvious absence unexpected result. The rejection is maintained.
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.
The rejection of Claims 13, 15, 16, 17 and 18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph are moot in view of the new ground of rejection.
Claims 25 and 33 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. In the instant case, the explanation of the ground of rejection for claim 25 will be the same as the one explained in the previous office action on paragraphs 72-79. The full scope of the claim 25 read on using any or all amino acid residue to replace or substitute the original amino acid resides located at position 64, 81, 84, 85 and 92 does not meet the written description under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
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.
/BAO Q LI/Primary Examiner, Art Unit 1671