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 11/4/2025.
Claims 16, 17, 19, 21-26, 31-34 and 36-39 are pending. Claims 32-34 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Claims 16, 17, 19, 21-26, 31 and 36-39 are under examination.
This application is continuation of International Application No. PCT/US2021/018868 filed February 19, 2021, which claims the benefit of U.S. Provisional Application Nos.: 62/979,309 filed February 20, 2020; 63/044,597 filed June 26, 2020; and 63/136,134 filed January 11, 2021.
Information Disclosure Statement
An IDS filed 11/4/2025 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through.
Response to amendments
Applicants amendments are sufficient to overcome the objections to the specification. The amendments are sufficient to overcome the previous objections as well as rejections under 35 USC 112, second and the rejection based upon double patenting as the copending claims do not claim an intracellular domain from LIR1.
Claim Objections
Claim 1 is objected to because of the following informalities: for consistency, reference to “the intracellular signaling domain” in claims 19, 34 and 36 should be amended to recite as in claim 16 –at least one of the one or more intracellular signaling domains--.
As well, due to the amendment, the term “target tumor” should recite –tumor targeted by the chimeric receptor--. The receptor is on a cell that targets a tumor more properly. These are new observations.
Appropriate correction is required.
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 16, 17, 19, 21-25, 26, 31 and 36-37 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kamb et al (WO 2021/119489). This is a new rejection necessitated by applicants amendment.
Kamb et al provide details of the instant invention as amended. Figure 13B depicts hinge, transmembrane and intracellular domains from LIR-1 also known as LIR1 or LILRBA (see ¶0063, ¶0281 and Figure 13). The sequences are part of an inhibitory CAR (see ¶0015), of an inhibitory CAR NK cells (see page 1, ¶0003 also relevant for claim 26). The construct comprises an extracellular LBD as well (see page 4, ¶0013). The construct blocks activation (¶0288)
[0285] A variety of potential inhibitor (blocker) receptor constructs were screened, and the LIR-1 blocker constructed was discovered to have stronger blocking properties than PD-i and CTLA-4. This blocker receptor includes the intracellular, transmembrane (TM) and hinge domains of the LIR-1 (LILRB1) receptor, one of several LIR-family molecules encoded by the human genome. The LIR-1 blocker (henceforth referred to as LIR-1) fused to the NY-ESO-1 LBD mediated an EC50 shift of >5,000x (FIG. 14B, FIGS. 17A-17D).
The disclosure has the option of using an extracellular domain not from LIR1 which means the use of an extracellular domain from LIR1 is encompassed in the alternative.
As to claim 19, the sequence is 100% related to SEQ ID NO:50 (see page 61). This encompasses claim 36.
unnamed protein product
Sequence ID: Query_2551363Length: 168Number of Matches: 1
Range 1: 1 to 168GraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Method
Identities
Positives
Gaps
339 bits(869)
2e-126
Compositional matrix adjust.
168/168(100%)
168/168(100%)
0/168(0%)
Query 1 LRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKHTQPE 60
LRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKHTQPE
Sbjct 1 LRHRRQGKHWTSTQRKADFQHPAGAVGPEPTDRGLQWRSSPAADAQEENLYAAVKHTQPE 60
Query 61 DGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTE 120
DGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTE
Sbjct 61 DGVEMDTRSPHDEDPQAVTYAEVKHSRPRREMASPPSPLSGEFLDTKDRQAEEDRQMDTE 120
Query 121 AAASEAPQDVTYAQLHSLTLRREATEPPPSQEGPSPAVPSIYATLAIH 168
AAASEAPQDVTYAQLHSLTLRREATEPPPSQEGPSPAVPSIYATLAIH
Sbjct 121 AAASEAPQDVTYAQLHSLTLRREATEPPPSQEGPSPAVPSIYATLAIH 168
As well, and as recited in claim 21, the transmembrane domain comprises SEQ ID NO:59 This encompasses claim 37.
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605
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The extracellular domain such as an antigen binding domain as recited in claim 23 can bind to an antigen not on cancer cells (see e.g. ¶0168) as recited in claim 22.
Claim 24 requires a spacer between the extracellular protein binding domain and the transmembrane domain. The spacer is from CD8, CD4, CD7, CD28, IgG1, IgG4, FCgRIIIa, LNGFR, PDGFR. To this end, a hinge is a spacer region. Kamb et al teach a hinge that is CD28 or CD8a (see e.g., 0125). between the extracellular domain and the transmembrane domain (see e.g. ¶ Figure 2)
The inhibitory based CAR can also targets TCR as recited in claim 25 (see Figure 12B wherein KRAS is targeted).
Pharmaceutical compositions are encompassed (see ¶0222).
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 16, 17, 19, 21-26, 31 and 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Kamb et al (WO 2021/119489) in view of Boroughs et al (US 20220170097). This is a new rejection necessitated by applicants amendment.
Kamb does not provide teachings of a spacer between the TM and the intracellular domain. However, such linkage was known and used in the art. For example, Boroughs teaches use of a number of the claimed spacers between these domains, see ¶0177 and 0207.
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 the known sequences used for similar compositions in the iCARs of Boroughs in the constructs of Kamb. Such a modification would have resulted in a inhibitory receptor cells of claims 38 and 39. As noted above: 1) Boroughs et al teach the claimed iCARs but do not include spacers between the iCAR TM and ISD 2) Boroughs teaches insertion of such a sequence is known and predictably successful. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the inclusions of such sequences would have been obvious.
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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634
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