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 .
Applicant’s election without traverse of group I and the species: a first and second virus, Cas nuclease, cardiac progenitor cell, under 30 years of age, and AAV serotype 9 in the reply filed on 1/29/24 is acknowledged.
It is noted that the claims have been amended to be directed to a method in any postnatal subject.
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 (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 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.
Claim(s) 1, 5, 9, and 11 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Schneider et al. (WO 2016/196350 A1)
It is noted that instant claim 11 recites an outcome rather than a method step and the outcome is considered to necessarily flow from the method steps.
Schneider et al. teach: [0045] As described in more detail below, compositions according to the present invention are useful in gene therapy, which includes both ex vivo and in vivo techniques. Thus, host cells can be genetically engineered ex vivo with a nucleic acid molecule (or polynucleotide), with the engineered cells then being provided to a patient to be treated. Delivery of the active agent of a composition described herein in vivo may involve a process that effectively introduces a molecule of interest {e.g., AUF1 protein or a functional fragment thereof) into the cells or tissue being treated
Schneider et al. teach: [0063] The present invention also contemplates the intracellular introduction of the polynucleotide (i.e., encoding AUF1 protein or a functional fragment thereof) and subsequent incorporation within host cell DNA for expression by homologous recombination using techniques described above or by use of genome editing or alteration. Such techniques for targeted genomic insertion involve, for example, inducing a double stranded DNA break precisely at one or more targeted genetic loci followed by integration of a chosen transgene or nucleic acid molecule (or construct) during repair. Such techniques or systems include, for example, zinc finger nucleases ("ZFN"), transcription activator-like effector nucleases ("TALEN"), clustered regularly interspaced short palindromic repeat ("CRISPR")-associated endonucleases (e.g., CRISPR/ CRISPR-associated ("Cas") 9 systems) (instant claim 5).
Schneider et al. teach: [0064] Another aspect of the present invention relates to a composition comprising a muscle satellite cell population, where the cell population comprises a transgene exogenous to the satellite cells and encoding AUF1 protein or a functional fragment thereof.
Schneider et al. teach: [0076] Accordingly, in one embodiment, the nucleic acid molecule encodes an endonuclease for targeted alteration of genes encoding a target (e.g., MMP-9, Twistl, cyclin Dl, IL17, MMP-8, IL10, FGR, TREMl, CCR2, ADAM8, or ILlb). In one embodiment, the nucleic acid molecule encodes an endonuclease for targeted alteration of genes encoding MMP-9, Twistl, cyclin Dl, or a combination thereof. The nucleic acid molecule may encode an endonuclease for targeted alteration of the gene encoding IL17, MMP-8, IL10, FGR, TREMl, CCR2, ADAM8, or ILlb. The endonuclease may be a ZFN, TALEN, or CRISPR-associated endonuclease.
Schneider et al. teach: [0114] A further aspect of the present invention relates to a method of causing satellite- cell mediated muscle generation in a subject. This method involves selecting a subject in need of satellite-cell mediated muscle generation and administering to the selected subject (i) a composition of the present invention, (ii) a cell population of the present invention, (iii) AUF1 protein, a functional fragment of AUF1 protein, an AUF1 protein mimic, or a combination thereof , or (iv) a combination of (i), (ii), and (iii), under conditions effective to cause satellite- cell mediated muscle generation in the selected subject. In one embodiment, the administering is carried out by injection of (i), (ii), (iii), or (iv) into the muscle.
Schneider et al. teach: [0118] Therapeutic applications include administering a composition to a subject in need of regeneration of lost or damaged muscle tissue, for example, after muscle injury, or in the treatment or management of diseases and conditions affecting muscle. In some embodiments, the disease or condition affecting muscle may include a wasting disease (e.g., cachexia), muscular attenuation or atrophy (e.g., sarcopenia), ICU-induced weakness, prolonged disuse (e.g., coma, paralysis), surgery-induced weakness (e.g., following joint replacement), or a muscle degenerative disease (e.g., muscular dystrophies or other myopathies).
Schneider et al. teach: [0121] The subject may be a mammal. In one embodiment, the subject is a human. In another embodiment, the subject is a rodent.
Schneider et al. teach: [0129] Another aspect of the present invention relates to a method of treating a subject in need thereof with Syndecan 4.sup.+/PAX7.sup.+ or Syndecan 4.sup.+/ PAX7.sup." muscle satellite cells expressing exogenous AUF1 . This method involves administering Syndecan 4.sup.+/PAX7.sup.+ or Syndecan 4.sup.+/ PAX7.sup." muscle satellite cells transformed or transfected with a nucleic acid molecule encoding exogenous AUF1 or a functional fragment thereof, where the Syndecan 4.sup.+/PAX7.sup.+ or Syndecan 4.sup.+/ PAX7.sup." muscle satellite cells express the exogenous AUF1 or the functional fragment thereof in an in vitro or an in vivo model.
Therefore, Schneider et al. teach delivery of a nucleic acid molecule that encodes an endonuclease for targeted alteration of a gene, wherein the endonuclease is a ZFN, TALEN, or CRISPR-associated endonuclease to satellite cells. Schneider et al. teach that the method can be practiced in vivo in a postnatal subject. Schneider et al. teaches a method of intracellular introduction of the polynucleotide (i.e., encoding AUF1 protein or a functional fragment thereof) (meeting the instant limitation of donor template) and subsequent incorporation within host cell DNA for expression by homologous recombination using techniques described above or by use of genome editing or alteration (instant claim 1).
Schneider et al. teach that the satellite cells are PAX7+ ([0148], [0167],[0170], [0172])(instant claim 9).
Schneider et al. teach that the virus is an adenovirus or adeno-associated virus (claims 11 and 12).
Therefore, the claims are anticipated by Schneider et al.
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 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.
Claim(s) 2-4, 12, 13, 16-22, 25, and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schneider et al. (WO 2016/196350 A1) as applied to claims 1, 9, and 11, above, and further in view of Chew et al. (Nature Methods, 2016, 13, 10, 868-879), and Tabebordbar et al. (Science, 2016, 351, 6271, 407-411), Zhang (US 2017/0152528 A1), and Kamdar et al. (Journal of the American College of Cardiology, 67, 21, 2016, 2533-2546).
The Tabebordbar et al., Zhang, and Kamdar et al. references are of record and previously cited.
It is noted that instant claims 11 and 26 recite outcomes rather than a method step and the outcomes are considered to necessarily flow from the method steps.
Schneider et al. teach delivery of a nucleic acid molecule that encodes an endonuclease for targeted alteration of a gene, wherein the endonuclease is a ZFN, TALEN, or CRISPR-associated endonuclease to satellite cells. Schneider et al. teach that the method can be practiced in vivo in a postnatal subject. Schneider et al. teaches a method of intracellular introduction of the polynucleotide (i.e., encoding AUF1 protein or a functional fragment thereof) (meeting the instant limitation of donor template) and subsequent incorporation within host cell DNA for expression by homologous recombination using techniques described above or by use of genome editing or alteration (instant claim 1).
However, Schneider et al. does not specifically disclose: wherein the one or more viruses comprise a first virus which transduces a nucleic acid sequence encoding a sequence-targeting nuclease and a donor template; wherein the one or more viruses comprise a first virus which transduces a nucleic acid sequence encoding a sequence-targeting nuclease, and a second virus which transduces a donor template; or wherein the one or more viruses comprise a first virus which transduces a nucleic acid sequence encoding a sequence-targeting nuclease, and a second virus which transduces a donor template and one or more gRNAs (instant claims 2-4).
It would have been a matter of design choice for the nucleic acid sequence encoding a sequence-targeting nuclease and a donor template to be delivered via a single vector or two separate vectors. It is routine in the field to deliver functional sequences encoding the intended product, as evidenced by the nucleic acid encoding the nuclease of Schneider et al.
For example, Zhang teaches: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition (abstract). Zhang teaches that the vector can be an AAV vector [0032].
[0179] Single Virus Vector:
[0180] Vector containing two or more expression cassettes:
[0181] Promoter-Cas9 coding nucleic acid molecule-terminator
[0182] Promoter-gRNA1-terminator
[0183] Promoter-gRNA2-terminator
[0184] Promoter-gRNA(N)-terminator (up to size limit of vector)
[0185] Double Virus Vector:
[0186] Vector 1 containing one expression cassette for driving the expression of Cas9
[0187] Promoter-Cas9 coding nucleic acid molecule-terminator
[0188] Vector 2 containing one more expression cassettes for driving the expression of one or more guide RNAs
[0191] To mediate homology-directed repair. In addition to the single and double virus vector approaches described above, an additional vector is used to deliver a homology-direct repair template.
Zhang teaches: [0208] Viral delivery: The CRISPR enzyme, for instance a Cas9, and/or any of the present RNAs, for instance a guide RNA, can be delivered using adeno associated virus (AAV), lentivirus, adenovirus or other viral vector types, or combinations thereof. Cas9 and one or more guide RNAs can be packaged into one or more viral vectors.
Zhang is therefore evidence that one or ordinary skill in the art would have known to deliver more than one of the components could be contained within a single vector or two vectors. Therefore, it would have been obvious to deliver sequences encoding the Cas9 and donor template in the same virus vector; to deliver sequences encoding the Cas9 and the donor template in separate vectors, or to deliver a sequence encoding Cas9 in one vector and sequences encoding the donor template and a gRNA in another virus with expectation of successful delivery to the target cell.
With regards to the addition of a gRNA and the AAV serotype being AAV9, Chew et al. teach AAV9 delivery of Cas9:gRNA for genome editing. Therefore, it would have been obvious to select AAV9 and incorporate a gRNA with the expectation of effective activity (instant claims 4 and 12).
In view of Schneider et al., it was known to deliver the instant construct in a postnatal subject. Selection of a subject that is a juvenile is considered to be a matter of design choice as the age of the subject would depend upon the age of the patient that needs to be treated (instant claim 13).
Additionally, selection of a cardiac cell or a specific species of cardiac cells is considered to be a matter of design choice because the method of Schneider et al. of editing a genome could be applied to cardiac cells if the desired target is in a cardiac cell, as evidenced by Tabebordbar et al. who evidences targeting cardiac cells with Cas9/gRNAs via AAV9 for DMD.
It would have been obvious for the cardiac cell to by a cardiomyocyte or precursor thereof because Kamdar et al. teaches that cardiac muscle is also a subtype of striated muscle and is similarly affected in many of the muscular dystrophies. Kamdar et al. teach that cardiomyopathies associated with dystrophinopathies are an increasingly recognized manifestation of these neuromuscular disorders and contribute significantly to their morbidity and mortality. Kamdar et al. teach that recent studies suggest that these patient populations would benefit from cardiovascular therapies, annual cardiovascular imaging studies, and close follow-up with cardiovascular specialists. Kamdar et al. teach that moreover, patients with DMD and BMD who develop end-stage heart failure may benefit from the use of advanced therapies. Kamdar et al. teach that this review focuses on the pathophysiology, cardiac involvement, and treatment of cardiomyopathy in the dystrophic patient (abstract). Kamdar et al. teach skeletal muscle and heart lacking functional dystrophin are mechanically weak, and contraction of the cell (skeletal myocytes and cardiac myocytes) leads to membrane damage (page 2534).
This is evidence of a scenario when these cell types would be selected for the method of Schneider et al.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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