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 .
Claim status
Claims 1-14, 16-18, 20-22 are pending.
Claims 12-14, 16-18, 20-22 are withdrawn.
Claims 15 and 19 are cancelled.
Claims 1-11 are under examination.
Election/Restrictions
Applicant's election without traverse of invention group 1, drawn to recombinant self-complementary adeno-associated virus (scAAV) vector, claims 1-11, in the reply filed on 3/9/2026 is acknowledged.
Applicant elected the species C. Eukaryotic promoter, hybrid chicken beta actin (CBh) recited in claim 4, and AAV2 recited in claim 7.
Claims 12-14, 16-18, 20-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species/invention.
Claims 15 and 19 are cancelled.
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 4-6 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 4-6, the phrase "for example" or “e.g.” renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Therefore the claims 4-6 and the dependent claim 11 which is dependent on claim 6 are rejected under 135 U.S.C. 112 b.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 5-9, 11 are rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez-Estevez et al., Gene therapy 27.3 (2020): 127-142, in view of Bass et al.(US 2020/0261550 A1).
Regarding claim 1, Rodriguez-Estevez, teaches a double-stranded self-complementary, adeno-associated virus (scAAV) (abstract, page 127and introduction page 128, first two lines), comprising capsid protein that can be used to treat intraocular pressure (IOP ) and glaucoma resulting from dysfunction of trabecular meshwork (TM) of the eye in humans (abstract, page 127).
Rodriguez-Estevez also teaches a scAAV2 viral genome comprising dominant-negative RhoA which can effectively reduce IOP in IOP elevated models of rat and sheep (introduction, paragraph 1, page 128).
Rodriguez-Estevez does not teach an eukaryotic promoter operably linked to a polynucleotide encoding dominant negative RhoA.
Bass teaches that dominant-negative RhoA gene can be operably linked to eukaryotic or prokaryotic promoters (paragraph 0114-0116), and the design of the expression vectors carrying dominant-negative RhoA gene, and its’ promoter will be a choice of those skilled in the art that design them and depends on the targeted tissue of anticipated expression (0114).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to modify the above-mentioned teachings of Rodriguez-Estevez that teaches a self-complementary, adeno-associated virus (scAAV), comprising an AAV capsid protein and dominant-negative RhoA polynucleotide, with Bass that teaches a eukaryotic promoter operably linked to a polynucleotide encoding dominant negative RhoA. One of Ordinary skill in the art would have been motivated to combine the teachings of Rodriguez-Estevez and Bass to produce a scAAV particle carrying dominant negative RhoA polynucleotide that can transduce ocular tissue, for effective gene therapy for IOP and glaucoma as taught by Rodriguez-Estevez. There would be a reasonable expectation of success to combine the teachings of Rodriguez-Estevez and Bass, because Rodriguez-Estevez teaches a method of producing a scAAV particle with a AAV capsid that can effectively transduce ocular tissue and Bass teaches the selection of a eukaryotic promoter customized to targeted tissue and the combined knowledge of Rodriguez-Estevez and Bass can be used to design a scAAV particle that can transduce ocular tissue with high efficiency.
Regarding claim 4, Bass teaches a recombinant scAAV particle comprising a polynucleotide encoding dominant negative RhoA linked to an eukaryotic promoter (paragraph 0114-0116, see claim 1 rejection). The recited limitations inside parenthesis in appear to be examples of promoter lengths and were not given patentable weight (please see 112b rejection). Since the specific promoters were recited as optional embodiments, they were not considered for the purposes of this art rejection.
Regarding claim 6, Rodriguez-Estevez teaches scAAV particles optimized for expression in ocular tissue, particularly in the TM (abstract, page 127).
Regarding claim 7, Rodriguez-Estevez teaches scAAV particle wherein the said particle comprises AAV2. scAAV2 showed the highest transduction efficiency in primary human TM cells compared to other serotypes (abstract, page 127, fig.1, page 129) .
Regarding claim 8, Rodriguez-Estevez teaches a scAAV particle wherein the capsid protein comprises one or more amino acid mutations or Y to F mutations that resulted in higher transduction efficiencies (results, capsid mutations of the highest transduction serotype increased transduction and viral entry, paragraph 1, page 130-131).
Regarding claim 9, teaches scAAV particle wherein one or three amino acid substitution mutations comprising either single Y444F or triple Y500F, Y730F, Y444F mutations respectively, numbered according to VP1 capsid are generated in scAAV2 particle (fig.3, page 131). scAAV2 is a known sequence in the art and VP1 is the largest of the three capsid proteins.
Regarding claim 11, Rodriguez-Estevez teaches scAAV particle that can be used to transduce the ocular tissue comprising trabecular meshwork or TM (abstract, page 127).
Regarding claims 2 and 3, Bass teaches methods of treating cancer using dominant negative RhoA polypeptide. Said dominant negative RhoA forms contain at least one amino acid mutation, particularly the said mutation is threonine to asparagine at position 19 or T19N (0005).
Hence, the claimed invention as a whole was prima facie obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez-Estevez and Bass as applied to claims 1-3, 5-9, and 11 above, and further in view of Seo, Hee et al., " BMC biotechnology 10.1 (2010): 69.
Teachings of Rodriguez-Estevez and Bass are as relied above.
Rodriguez-Estevez and Bass do not teach the eukaryotic promoter hybrid chicken beta -actin (CBh).
Regarding claim 4, Seo teaches CBh promoter for effective transgene expression in animal cells (Background, page 2). The CBh promoter consist of cytomegalovirus (CMV) enhancer/promoter and CAG (CMV enhancer with chicken beta-actin transcription start site and a rabbit beta-globin intron) which is about 1.3kb or 1300 nucleotides in length as evidenced by Miyazaki et al.1989.
The recited limitations inside parenthesis appear to be examples of promoter lengths and were not given patentable weight (please see 112b rejection).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to modify the above mentioned teachings of Rodriguez-Estevez that teaches a self-complementary, adeno-associated virus (scAAV), comprising an AAV capsid protein and dominant-negative RhoA polynucleotide, Bass that teaches an eukaryotic promoter operably linked to a polynucleotide encoding dominant negative RhoA, with Seo that teaches the use of eukaryotic CBh promoter for transgene expression in animal cells. One of ordinary skill in the art would have been motivated to combine the teachings of Rodriguez-Estevez, Bass and Seo to produce scAAV2 carrying dominant negative RhoA operably linked to a eukaryotic CBh promoter, for the efficient expression of dominant negative RhoA in animal cells, leading to an effective gene therapy for IOP and glaucoma as taught by Rodriguez-Estevez. There would be reasonable expectation of success to combine the teachings of Rodriguez-Estevez, Bass, and Seo because their combined knowledge teaches how to design a scAAV2 particle carrying dominant negative RhoA linked to an operable eukaryotic promoter that can be expressed in wide range of eukaryotic cells.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez-Esteve and Bass as applied to claims 1-3, 5-9, 11 above, and further in view of Fath, Stephan, et al., PloS one 6.3 (2011): e17596.
Teachings of Rodriguez-Esteve and Bass are as relied on above.
Rodriguez-Esteve and Bass do not teach a recombinant scAAV with codon optimized dominant negative RhoA polynucleotide to express in humans.
Regarding claim 5, Fath teaches a method of codon optimization in various candidate genes to express in mammalian cells including human HEK293T cell line (abstract, page e17596,). Fath obtained human gene sequences from NCBI GeneEntrez database and the coding regions were optimized using a software and the optimized sequences were synthesized using synthetic oligonucleotides prior to sequence verification (materials and methods, construct design and optimization, page, e17596).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to modify the above mentioned teachings of Rodriguez-Estevez that teaches a self-complementary, adeno-associated virus (scAAV), comprising an AAV capsid protein and dominant-negative RhoA polynucleotide, Bass that teaches an eukaryotic promoter operably linked to a polynucleotide encoding dominant negative RhoA, with Fath that teaches codon optimization to express genes in human cells. One of ordinary skill in the art would have been motivated to combine the teachings of Rodriguez-Estevez, Bass and Faith to produce scAAV2 particles carrying dominant negative RhoA polynucleotide optimized for expression in humans to effectively treat IOP and glaucoma. There would be a reasonable expectation of success to combine the teachings of Rodriguez-Estevez, Bass, Fath because their combined knowledge teaches how to design a scAAV2 particles that can efficiently transduce human ocular tissue, and effectively express dominant negative RhoA polynucleotide in the said tissue.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez-Esteve and Bass as applied to claims 1-3, 5-9, 11 above, and further in view of Petrs-Silva, Hilda, et al.,
Molecular therapy 17.3 (2009): 463-471.
Teachings of Rodriguez-Esteve and Bass are as relied on above.
Rodriguez-Esteve and Bass do not teach scAAV particles with one more amino acid mutations resulting in reduced immunogenicity and/or increased expression of the dominant negative RhoA.
Petrs-Silva teaches the use of tyrosine to phenylalanine mutant AAV particles such as AVV2, Y444F in lower titers to achieve efficient levels of transduction which enables reduced immunological response against the viral capsid (discussion, last paragraph, page 469).
Rodriguez-Estevez teaches high transduction efficiency in Y to F single or triple mutant scAAV2 particles (fig.4, page 132). Therefore it will be possible to use low titer Y to F mutant scAAV2 to achieve the desired transduction efficiency and reduce the associated immunogenicity.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to modify the above mentioned teachings of Rodriguez-Estevez that teaches a self-complementary, adeno-associated virus (scAAV), comprising an AAV capsid protein and dominant-negative RhoA polynucleotide, Bass that teaches an eukaryotic promoter operably linked to a polynucleotide encoding dominant negative RhoA, with Petrs-Silva teaches the use of Y to F mutant AAV particles such as AVV2, Y444F in lower titers to achieve efficient levels of transduction which enables reduced immunological response against the viral capsid. One of ordinary skill in the art would have been motivated to combine the teachings of Rodriguez-Estevez, Bass and Petrs-Silva to produce scAAV2 with desired Y to F mutations to achieve efficient transduction with lower titers that result in reduced immunogenicity, leading to effective gene therapy for IOP and glaucoma. There would be a reasonable expectation of success to combine the teachings of Rodriguez-Estevez, Bass, Petrs-Silva because their combined knowledge teaches how to design a scAAV2 particles with desired Y to F mutations that can transduce ocular tissue with high efficiency, and low immunogenicity.
Hence, the claimed invention as a whole was prima facie obvious.
Conclusion
No claim was allowed.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/ Examiner, Art Unit 1632
/PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632
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