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 .
Claims 1, 4, 5, 7-12, 14-18, 20, 21 and 24 are pending in the application. Claims 10-12, 14-18, 20, 21 and 24 are withdrawn. Claims 1, 4, 5, 7-9 are currently under examination.
This office action is in response to the amendment filed on 7/7/2026.
All previous rejection not reiterated in this office action is withdrawn.
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.
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) 1, 4, 8 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cathomen, in view of Maeder (WO 2015/148670). This rejection is necessitated by amendment.
Cathomen teaches introducing nucleic acid reagents encoding CCR5 sequence specific reagents into hematopoietic primary cells, alone or in combination with exogenous coding sequences, to make those cell resistant to HIV infection. Cathomen teaches vectors, polynucleotides and polypeptides encoding CCR5 specific reagents and resulting primary cells anti-HIV therapy (page 4, last paragraph, and page 5, 1st paragraph). Cathomen teaches the expression of CCR5 in hematopoietic stem cell (HSC) is reduced by more than 50%-75% (page 16-17 bridging paragraph). Cathomen teaches a preferred embodiment of the engineered cells are primary immune cells such as NK cells or T cells that are CCR5 negative (page 31, lines 6-12). Cathomen teaches using CRISRP-Cas9 and gRNA listed in Table 1, or TALEN for generating CCR5 with reduced expression (page 13, 1st and 2nd paragraph, and Table 1). It is well known that nucleases that results using NHEJ pathway would introduce indels (small insertion or deletion) which meets the limitation of deletion of at least one nucleotide and/or insertion of at least one nucleotide. Cathomen teaches the sequence specific reagents of their invention overcome most limitations of former reagents by targeting specific allelic sequence encoding the N-terminal region of CCR5 (page 4, lines 29-31). As shown in Figure 1, the T3 target site is within the first 15 amino acids of CCR5, which is encoded by exon 2.
However, Cathomen does not teach gRNA having sequence as SEQ ID NO: 1, 2 and 3 as claimed.
Maeder teaches gRNAs that target CCR5 domains that comprises sequences having 100% homology with SEQ ID NO: 1-3. Maeder teaches new guide RNA molecule comprises a targeting domain which is complementary with a target domain from CCR5 gene, SEQ ID NO: 503 (complementary to SEQ ID NO: 1), SEQ ID NO: 421 (complementary to SEQ ID NO: 2), and SEQ ID NO: 491 (complementary to SEQ ID NO: 3) (see attached alignment) (page 94-86, Table 1C).
It would have been obvious to an ordinary skilled in the art to use prior art known gRNA to target CCR5 with CRISPR/Cas9 because Maeder teaches they can be used with a Cas9 molecule that gives double stranded cleavage. Maeder teaches the 3 gRNA sequences are selected based on their close proximity to the start codon (page 92, 1st paragraph). Using prior art known gRNAs for their intended purpose would have been obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 4, Cathomen teaches reagents that introduces stable and inheritable mutations into CCR5 alleles and also reagents preventing expression, transcription or translation of CCR5 (page 12, line 6-9), wherein reagents prevents transcription inherently decreases mRNA encoding CCR5.
Regarding claim 8, Cathomen teaches chimeric antigen receptor (CAR) can be expressed into the primary hematopoietic cells in which the expression of CCR5 has been reduced or inactivated, wherein the polynucleotide sequence encoding CAR can be inserted at the CCR5 locus (page 17, line 26-30). Cathomen teaches expressing CAR directs or improve specificity of primary immune cells such as T cells and NK cells toward tumor of infected cell (page 17, lines 7-10).
Regarding claim 9, Cathomen teaches a therapeutic composition that comprises said modified cell and carrier (page 34, 2nd paragraph).
Claim(s) 5 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cathomen, in view of Maeder as applied to claims 1, 4, 8 and 9, in further view of Moriarity (US 2020/0208111, IDS). This rejection is necessitated by amendment.
The teaching from Cathomen and Maeder has been discussed above.
However, Cathomen and Maeder does not teach modification of NK cell further comprises a heterologous nucleic acid encoding CXCR4, CCR7, CXCR3 or combination thereof (claim 5), which result increased expression of said chemokine receptor. Cathomen does not teach further reduce expression of CXCR6, CCR1 or CD38 or a combination thereof in NK cells (claim 7).
Moriarity teaches genome edited primary NK cell that includes editing a gene for at least one of an activating receptor, an inhibitory receptor, a cytokine, a chemokine receptor…etc (paragraph [0009]). Moriarity teaches one embodiment is that a modification that alters cytokine or chemokine production relative to non-edited primary cell (page 3, paragraph [0050]). Morirarity teaches said modification may include a modification including CCR1, CCR4, CCR5, CCR7 and CXCR3, CXCR6 (paragraph [0051]).
It would have been obvious to an ordinary skilled in the art that the NK cells rendered obvious by Cathomen and Maeder may be further modified to include modification to chemokine receptor taught by Moriarity including CCR1, CCR4, CCR5, CCR7 and CXCR3, CXCR6 (paragraph [0051]). The ordinary skilled in the art would make such modification to alter the production of a particular chemokine (claims 5, increase production vs. claim 7, reduce production) as suggested by Moriarity. Since both Cathomen, Maeder and Moriarity provides reagents and methods for making such modification, an ordinary skilled in the art would have reasonable expectation of success to make such modification in NK cells as claimed. Therefore, the claimed invention of claims 5 and 7 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Conclusion
THIS ACTION IS MADE FINAL. 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 CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CELINE X QIAN/ Primary Examiner, Art Unit 1637
Prosecution Insights