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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/173,662 on 04/12/2021.
All claims are given the priority date of 04/12/2021.
Application Status
Receipt is acknowledged of amendment, filed 06/05/2024. Claims 1-3, 5-7, 16, 19-21, 23-25, 27, 30-34 and 36 are currently pending.
Election/Restriction
Applicant’s election of Group II, drawn to claims 19-21, 23-25, 27 and 30-34, in the reply filed on 06/01/2026 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Claims 1-3, 5-7, 16 and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/01/2026.
Therefore, claims 19-21, 23-25, 27 and 30-34 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 01/18/2024 have been received and all references have been considered.
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 31-33 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.
Claim 31 is vague and indefinite in that the metes and bounds of the phrase “the gRNA comprises, consists essentially of, or consists of a nucleic acid sequence of 10-30 or 15-25 consecutive nucleotides of the sequence or a nucleotide sequence of 10-30 or 15-25 nucleotides capable of specifically hybridizing to an equal-length portion of the sequence” are unclear. The phrase is unclear in that it is unknown if the sequences provided are required for the structure or function of the gRNA of the invention. It would be remedial to replace the phrase as currently claimed with the specific sequence of the gRNA being claimed or the specific sequence of the MYO7A gene wanting to be targeted.
Claim 32 is vague and indefinite in that the metes and bounds of the phrase “the gRNA comprises, consists essentially of, or consists of a nucleic acid sequence of, or capable of specifically binding to any one of the sequences” are unclear. The phrase is unclear in that it is unknown if the sequences provided are required for the structure or function of the gRNA of the invention. It would be remedial to replace the phrase as currently claimed with the specific sequence of the gRNA being claimed or the specific sequence of the MYO7A gene wanting to be targeted.
Claim 33 is vague and indefinite in that the metes and bounds of the phrase “the gRNA comprises, consists essentially of, or consists of a nucleic acid sequence of 10-30 or 15-25 consecutive nucleotides of the sequence or a nucleotide sequence of 10-30 or 15-25 nucleotides capable of specifically hybridizing to an equal-length portion of the sequence” are unclear. The phrase is unclear in that it is unknown if the sequences provided are required for the structure or function of the gRNA of the invention. It would be remedial to replace the phrase as currently claimed with the specific sequence of the gRNA being claimed or the specific sequence of the MYO7A gene wanting to be targeted.
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.
Claims 19-21, 27, 30 and 32 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Glucksmann et al (US 2021/0040506 Al; Published: 02/21/2021).
Regarding claim 19, Glucksmann teaches a composition comprising a CRISPR-associated endonuclease (Cas9), a guide RNA and a template nucleic acid wherein the gRNA targets a MYO7A gene ([1545 and 1559]; Claims 259 and 277).
Regarding claims 20 and 21, Glucksmann teaches the composition is delivered in a delivery vehicle wherein the delivery vehicle is a secretory exosome [1037].
Regarding claim 27, Glucksmann teaches a composition comprising a CRISPR-associated endonuclease (Cas9), a guide RNA and a template nucleic acid wherein the gRNA targets a MYO7A gene ([1545 and 1559]; Claims 259 and 277).
Regarding claim 30, Glucksmann teaches the template nucleic acid comprises a nucleotide that corresponds to a nucleotide of the target position from a sequence of a gene, MYO7A [0019, 1545 and 1559].
Regarding claim 32, the claim is interpreted that “a sequence” means two or more consecutive amino acids/nucleotides and not the entirety of the sequence.
Glucksmann teaches the guide RNA sequence of SEQ ID NO: 5 is 100% identical to two or more consecutive nucleotides to instant SEQ ID NO: 17 (See Appendix I and [0419]).
Claims 19, 27 and 30-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang et al (Stem Cells Transl Med. 2016 May;5(5):561-71).
Regarding claims 19 and 27, Tang teaches one MY07A mutation locus (c.4118C> T) in the iPSCs induced from the patient was genetically corrected using the CRISPR-Cas9 system to establish a new iPSC line (Page 562, Column 1). Tang teaches gRNAl was selected for all subsequent experiments because of its relatively higher disorder peak rate and because its cutting site was only 8-base pair (bp) from the site to be corrected (Page 563, Column 2 bridging Page 564, Column 1).
Regarding claim 30, Tang teaches iPSCs were generated from the urinary cells of the deaf patient with compound heterozygous MY07A c.1184G>A and c.4118C>T mutations (P-iPSCs), the patient's asymptomatic father with a MY07A c.1184G>A mutation (CF-iPSCs), and a healthy donor with normal MY07Awt/wt (C-iPSCs) (Page 562, Column 1).
Regarding claim 31, Tang teaches one MY07A mutation locus (c.4118C> T) in the iPSCs induced from the patient was genetically corrected using the CRISPR-Cas9 system to establish a new iPSC line (Page 562, Column 1). Tang teaches gRNAl was selected for all subsequent experiments because of its relatively higher disorder peak rate and because its cutting site was only 8-base pair (bp) from the site to be corrected (Page 563, Column 2 bridging Page 564, Column 1). Tang teaches the sequence of sgRNA 1 which is 100% complementary to at least 15 consecutive nucleotides of instant SEQ ID NO: 7 (See Appendix II; Page 30, Table S1).
Regarding claim 32, the claim is interpreted that “a sequence” means two or more consecutive amino acids/nucleotides and not the entirety of the sequence.
Tang teaches the sequence of sgRNA1 which is 100% identical to two or more consecutive nucleotides of instant SEQ ID NO: (See Appendix III; Page 30, Table S1).
Regarding claim 33, Tang teaches one MY07A mutation locus (c.4118C> T) in the iPSCs induced from the patient was genetically corrected using the CRISPR-Cas9 system to establish a new iPSC line (Page 562, Column 1). Tang teaches gRNAl was selected for all subsequent experiments because of its relatively higher disorder peak rate and because its cutting site was only 8-base pair (bp) from the site to be corrected (Page 563, Column 2 bridging Page 564, Column 1). Tang teaches the sequence of sgRNA 1 which is 100% complementary to at least 15 consecutive nucleotides of instant SEQ ID NO: 1 (See Appendix IV; Page 30, Table S1).
Regarding claim 34, Tang teaches one MY07A mutation locus (c.4118C> T) in the iPSCs induced from the patient was genetically corrected using the CRISPR-Cas9 system to establish a new iPSC line wherein the MYO7A gene is a human MYO7A gene (Page 561, Abstract and Page 562, Column 1). Tang teaches gRNAl was selected for all subsequent experiments because of its relatively higher disorder peak rate and because its cutting site was only 8-base pair (bp)
from the site to be corrected (Page 563, Column 2 bridging Page 564, Column 1).
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.
Claims 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Glucksmann et al (US 2021/0040506 Al; Published: 02/21/2021) in view of Bosch et al (Sci Rep 6, 36162 (2016); Pgs. 1-11).
The teachings of Glucksmann are as described and applied above.
Regarding claims 23-25, Glucksmann does not teach the use of a destabilizing agent associated with the extracellular vehicle, specifically that the destabilizing agent is a disaccharide, more specifically, trehalose.
Bosch teaches trehalose as a natural, non-toxic dispersion agent and cry oprotectant to preserve stability of ELV suspensions using protein, PSD, cryo-electron tomography, zeta potential, and cytokine secretion analyses (Page 5, Paragraph 5). Bosch teaches TRE (25 mM) is simply added to extracellular vesicle isolation which generates a significantly higher particle count with reduced mean size and spread as shown by NTA, compared to PBS (Page 5, Paragraphs 5-6 bridging Page 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Glucksmann to include the destabilizing agent, trehalose, with the exosome as taught by Bosch because Glucksmann teaches it is within the ordinary skill in the art to use a composition comprising a CRISPR-associated endonuclease (Cas9), a guide RNA and a template nucleic acid wherein the gRNA targets a MYO7A gene wherein the composition is delivered in a delivery vehicle wherein the delivery vehicle is a secretory exosome and Bosch teaches trehalose as a natural, non-toxic dispersion agent and cry oprotectant to preserve stability of ELV suspensions using protein, PSD, cryo-electron tomography, zeta potential, and cytokine secretion analyses.
One would have been motivated to make such a modification in order to receive the expected benefit of trehalose as a destabilizing agent with exosome delivery for higher particle count and preserve stability of ELV suspensions as taught by Bosch.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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