DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 12/18/2025.
Claims 1, 4, 7-11, 15-17, 19, 30, 32, 33, 43, 45-51, 55 and 59 are pending.
This application claims priority under 371 to PCT/US2021/055315 filed 10/15/2021 which claims priority to provisional application 63/092,433 filed 10/15/2020.
Information Disclosure Statement
An IDS filed 12/17/2025 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action. The document under Foreign Patent Documents was crossed off and not considered. It lists as a corresponding publication WO 2014197748. But this latter document was not located in the file.
Response to Amendments
The substitute drawings sufficient to overcome the objections to the drawings. As well, objections to the claims have been overcome by amendment.
Claim Objections
Claims 4 are objected to because of the following informalities: claim 4 has a number of abbreviations that should be spelled out in full such as GLT, GRP, TANG, and SEC.
Claim 19 repeats lines 7-8 in lines 9-10. These are new observations.
Claim Rejections - 35 USC § 112, second paragraph
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, 4, 7-11, 15-17, 19, 30, 32, 43, 45-51, 55 and 59 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.
The dependent claims are included in the rejection because they fail to address or clarify the basis of the rejection as discussed in detail for the independent claims.
This is a new rejection necessitated by applicants’ amendment.
Claim 1 recites the limitation "the targeted gene" in line 5. There is insufficient antecedent basis for this limitation in the claim. There are references to “two or more targeted genes” and claim 27 does not clarify if it is all or only one and if one which one. Clarification should be further provided in the claims by reciting in line 12—wherein the two or more targeted genes are one or more--. The last 2 lines in the claim appear to be redundant as well with line 5. MPEP 2173 Clear Notice Requirement “Optimizing patent quality by providing clear notice to the public of the boundaries of the inventive subject matter protected by a patent grant ... “’“ ... to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent.”
This rejection is maintained.
Claim 4 recites that the cell is engineered to perform CRISPRa. It is unclear how a cell can perform CRISPRa. CRISPR is an enzyme that must be expressed to function with Cas and gRNA. Bit, the cell in the claim performs CRISPRa. It is unclear how this is mediated. This is true of claim 4. This issue is also initiated by the recitation in claim 19(b) that the cell “becomes capable” of expressing said dCas9 activator. It is not clear how the cell becomes capable. It appears elements are missing from the claims.
This rejection is maintained.
Claims 15, 16, 19, 30, 55 and 59 are vague and indefinite in that the metes and bounds of the term “derived from” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of a cell. The term implies a number of different steps that may or may not result in a change in the functional characteristics of from the source that it is “derived from”.
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 4 and 19 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection is maintained.
Claim 4 recites that the cell is engineered to perform CRISPRa. It is unclear how a cell can perform CRISPRa. CRISPR is an enzyme that must be expressed to function with Cas and gRNA. Bit, the cell in the claim performs CRISPRa. It is unclear how this is mediated. This issue is also initiated by the recitation in claim 19(b) that the cell “becomes capable” of expressing said dCas9 activator. It is not clear how the cell becomes capable. It appers elements are missing from the claims.
The disclosure teaches construction of a lentivirus or vectors encoding CRISPRa and Cas9 that are transduced or transfected into cell and the sequences are linked to a promoter. This is how the cell “performs” the CRISPRa. This transduction or transfection of vectors encoding the sequences comprising promoters is the only way that the cell completes the tasks as claimed. The gRNA is also encoded by a vector under control of a promoter. In some cases, the cells are integrated into the cell but these sequences still require promoters to mediate expression such that the event can be performed and the cell is capable of expression.
To this end, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
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 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.
Claims 1, 10, 11, 16, 17, 19, 32, 33, 43, 55 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Bowles et al (U.S. 20210380975) in view of Kuroda and Murata (each from the IDS filed 12/17/2025). This rejection is necessitated by applicants IDS’.
Bowles et al teaches an engineered cell (fibroblast) that is engineered with dCas9, one or more gRNAs wherein at least one targets COL2A1 with CRISPRa (see abstract and ¶ 0040, 0087, 0105). The effect is to upregulate collagen type II (see e.g. ¶0104).
Kuroda provided by applicants teach that collagen I and II are increased by the presence of TGF-b1 (see page 6, col 2). Murata also teach TGF-b3 increased collagen production up to 200% (see abstract). Hence, one would look to activation of this molecule to increase collagen biosynthesis in the system of Bowles et al. As Bowles teaches a need to upregulate collagen and both Kuroda and Murata teach use of TGF-b1 and TGF-b3 for this purpose, the combination of references makes obvious claim 1 of the instant claims.
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to include as one of the one or more gRNAs to enhance collagen. As noted above: 1) Bowles et al teach modifications of cells to increase collagen production by use of gRNAs; 2) Kuroda et al teach that collagen is increased with an increase (activation) of TGFb1 and 3) Murata et al teach that collagen is increased with an increase (activation) of TGFb3. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded method would allow improved collagen production.
As recited in claim 10 and 11, Bowles teaches use of VPR with dCAS9 (see ¶0106).
As regards claim 16, Bowles teaches the cell is from a subject in need thereof (see e.g. ¶0140). Alternatively, the cell can be from a cell culture as recited in claim 17 (see ¶0155). As recited in claim 19, the cell can be a fibroblast. A kit is included as are medical devices (see e.g. ¶0143) as recited in claims 32, 33 . As recited in claims 55 and 59, The cell is administered for treating a subject with lower back pain or arthritis. As cosmetic needs are not explicitly defined, it would appear that a person with any musculoskeletal deformity would meet the needs of a cosmetic therapy (see e.g., ¶0057).
Claims 15, 30, and 45-51 are rejected under 35 U.S.C. 103 as being unpatentable over Bowles et al (U.S. 20210380975) in view of Kuroda and Murata (each from the IDS filed 12/17/2025) as applied to claims 1, 7, 10, 11, 16, 17, 19, 32, 33, 43, 55 and 59 above, and further in view of Masoumi et al (US 20200085877) and Conrad et al (US 20020019349) and Shanks (US 20200331984). This rejection is necessitated by applicants IDS’.
Claims 15 and 30 require an engineered cell that is derived from a human corneal fibroblast. Shanks teaches that collagen increase is needed in defective human corneal fibroblasts (¶0168). Hence, these would be an ideal target for reprogramming.
Masoumi teaches a bioreactor for production of collagen that uses a modulat9or such as IGF and mechanical strain with scaffold (see e.g. ¶0031, 0039 and 0108) as recited in claims 45, 46, 50 and 51. This production like the cells of Bowles is to treat subjects with artificial tissues and such. Hence, one would look to the improved cell components of Bowles as a producer cell.
Growth conditions known for collagen include ascorbate and aminopropionitrile (see ¶0176, Conrad) as recited in claims 47-49.
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate cell of Bowles et al in view of Kuroda et al and Murata et al for the production of collagen with known conditions as set forth by Masoumi, Shanks and Conrad. Such a modification would have resulted in a method encompassed by the claims. As noted above: 1) Bowles et al teach modifications of cells to increase collagen production; 2) Kuroda and Murata direct one to create gRNA for TGFb1 3) Masoumi et al teach bioreactors to maximize collagen production 4) Conrad teaches growth conditions known for collagen production 5) one directs you to human corneal fibroblasts. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the expanded method would allow improved treatment.
Conclusion
Claim 4 and 7-9 are rejected but free of the art.
It is noted that sequences listed in claim 7 are found in the art (see sequences 243,499 which is SEQ ID NO:8 of the instant claims and 382,508 which is SEQ ID NO:11 in U.S. 20230042624). However, there is not indication that these sequences are designed specifically to target COL1A2 and TGF-b3.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 12/17/2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634