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 .
Election/Restrictions
Applicant’s election of Group I in the reply filed on 2/2/2026 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)).
Accordingly, claims 10-12, 14-18, 20, 21 and 24 are withdrawn from consideration for being directed to non-elected subject matter. Claims 1-9 are currently under examination.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more. The claim(s) recite(s) a modified ex vivo expanded natural killer cell (NK) comprising reduced expression of CCR5 compared to an unmodified ex vivo expanded NK cell. The closest counterpart of said NK cell is a cell that has reduced expression CCR5 because it has homozygous defect in CCR5 allele (Liu et al., Cell, 1996, vol. 86, pages 367-377, see abstract). This judicial exception is not integrated into a practical application because the claim does not recite any application of said NK cell. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because it only differs from the naturally occurring NK cell for being ex vivo expanded. However, ex vivo expansion does not result a significant structural difference between the claimed NK cell and the naturally occurring NK cell that has homozygous deletion of the allele. Similarly, placing the NK cell into a pharmaceutical carrier, for example, media, would not result in a significant structural difference. Therefore, the claimed NK cell of claims 1-3 and 9 is not eligible under 101.
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) 1-4, 8 and 9 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Cathomen (WO2018/189360, IDS).
Claim 1 is drawn to a modified ex vivo expanded natural killer (NK) cell comprising reduced expression of C-C chemokine receptor 5 (CCR5) compared to an unmodified NK cell.
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). Therefore, the teaching from Cathomen anticipates the claimed invention of claim 1.
Regarding claim 2, 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.
Regarding claim 3, 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.
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 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) 5-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cathomen, in view of Moriarity (US 2020/0208111, IDS).
The teaching from Cathomen has been discussed above.
However, Cathomen 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 (claim 6). 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 taught by Cathomen 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 and 6, increase production vs. claim 7, reduce production) as suggested by Moriarity. Since both Cathomen 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 5-7 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
No claims are allowed.
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).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637