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 .
Application Status
The amended claims filed with the Response to the non-final Office Action on March 31, 2026 are acknowledged. Claims 49, 53-55, 57-64, and 66-70 are pending. Claims 49, 62-63, and 70 are amended. Claims 57-58 and 66-67 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 49, 53-55, 59-64, and 68-70 are under consideration herein.
WITHDRAWN OBJECTIONS AND REJECTIONS
The prior grounds of objection over claims 62-63 and 70 are withdrawn in view of Applicant's claim amendments thereto.
The prior grounds of rejection over claim 63 under 35 U.S.C. § 112(b) are withdrawn in view of Applicant's claim amendment.
The rejection of claim 62 under 35 U.S.C. § 112(d) is withdrawn in view of Applicant's amendments to claim 49.
Applicant’s arguments, see Remarks at pages 9-13, filed March 31, 2026, with respect to the unexpected experimental results disclosed by Gang (Blood (2020) 136(20): 2308-2318; cited in IDS) have been fully considered and are persuasive. The rejections of claims 49, 52-55, 59-64, and 68-70 under 35 U.S.C. § 103 have been withdrawn.
Rejoinder
Claims 49, 53-55, 59-62, 64, and 68-70 are allowable. Claims 57-58 and 66-67, previously withdrawn from consideration as a result of an Election of Species requirement, require all the limitations of an allowable claim (in particular, claims 49 and 54). Pursuant to the procedures set forth in MPEP § 821.04(a), the Election of Species requirement, as set forth in the Office action mailed on May 22, 2024, is hereby withdrawn and claims 57-58 and 66-67 are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
In view of the withdrawal of the Election of Species requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
NEW OBJECTIONS AND REJECTIONS NECESSITATED BY CLAIM AMENDMENT
AND/OR REJOINDER
Claim Objections
Claim 66 is objected to for at least the following informalities:
The third step of the method (at line 6) recites “transducing the chimeric antigen receptor (CAR) of claim 49”. However, claim 49 is drawn to a “chimeric antigen receptor (CAR) memory-like natural killer (ML NK) cell”, which comprises a CAR construct. It is suggested that the preamble of the method claim could be amended to recite the CAR-ML NK cell of claim 49 instead.
It is suggested that “CAR-expressing ML NK (CARML NK cells)” in line 11 be amended for clarity and/or to address redundancy. It is noted that the preamble of the claim already recites that “CARML NK” refers to chimeric antigen receptor memory-like natural killer (CARML NK) cells.
Applicant's careful consideration and correction of the claimed method is requested.
Claim Rejections - 35 USC § 112(b)
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 57-58 and 63 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. This is a new rejection necessitated by claim amendment and/or rejoinder.
Claim 57 recites the limitation “the one or more integrins” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 49, from which claim 57 depends, does not recite “one or more integrins” to which the claimed limitations may refer.
In the interest of promoting compact prosecution, the Examiner suggests canceling claim 57.
Claim 58 recites transmembrane domains including “FCγRIIIa” (in lines 4-5), “NKp44” (in line 8), “NKp46” (in lines 9-10), “actKIR” (in line 11), and “NKG2C” (in line 12). Claim 58 further recites “a transmembrane domain and adapter combination”. There is insufficient antecedent basis for these limitations in the claim. With respect to the transmembrane domains, earlier claim 49 recites that the transmembrane domain is selected from CD8α, NKp30, and NKG2D. With respect to the “transmembrane domain and adapter combination”, earlier claims 49 and 54 recite that the CAR construct comprised in the CAR ML NK cell comprises an anti-CD19 scFv, a transmembrane domain, at least one intracellular signaling domain, and a hinge, but does not recite that the construct comprises a transmembrane adapter.
In the interest of promoting compact prosecution, the Examiner suggests canceling claim 58.
Claim 63 recites the limitation “the CD8α hinge” in lines 13 and 15. There is insufficient antecedent basis for these limitations in the claim. Neither claim 49 nor claim 53 earlier recite that the CAR construct comprised in the CAR ML NK cell comprises “a hinge” or “a CD8α hinge”.
In the interest of promoting compact prosecution, the Examiner suggests amending claim 63 to recite “a CD8α hinge” in place of “the CD8α hinge”.
Allowable Subject Matter
Claims 49, 53-55, 59-62, 64, and 67-70 are allowable.
The instantly claimed chimeric antigen receptor (CAR) memory-like natural killer (ML NK) cell of claim 49, comprising a CAR construct comprising (i) a targeting antibody fragment that is an anti-CD19 scFv, (ii) a transmembrane domain selected from CD8α, NKp30, and NKG2D, and (iii) at least one intracellular signaling domain selected from CD137, IL-15R, DNAM1, and 2B4, is found to be non-obvious over the cited prior art references of record. Applicant has presented persuasive Remarks and post-filing experimental evidence (Gang, supra) showing that a CAR-ML NK cell commensurate in scope with the instantly claimed invention shows significantly enhanced functional activity against NK-resistant lymphoma cell lines relative to conventional CAR-NK cells. In particular, Gang (supra) teaches that anti-CD19 CAR-expressing ML NK cells induce greater IFN-γ and CD107a responses and elicit significantly higher specific killing of CD19+ tumor cell lines compared to conventional anti-CD19 CAR-expressing NK cells (e.g., Gang at Results; Figures 1-4). These experimental findings could not have been predicted based on the teachings of Campana (US 2013/0266551 A1; cited in IDS), Shah (US 2019/0111080 A1; cited in PTO-892), or June (US 2015/0283178 A1; cited in PTO-892), further in view of Fehniger (Trends in Immunology (2016) 37(12): 877-888; cited in PTO-892).
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 Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
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