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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The present application is drawn from PCT/US2021/64408, filed 12/20/2021; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 63/129340, filed 12/22/2020.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 1-3, 5-6, 8-10 and 14-15, in the reply filed on 3/20/2026 is acknowledged. Claims 16-20 and 25-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II and III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/20/2026. Applicant’s election of species is acknowledged; applicants elected the extracellular domain of SEQ ID NO: 12, the transmembrane domain of SEQ ID NO: 5, the signaling domain of SEQ ID NO: 1, the full CAR construct of SEQ ID NO: 36 and nucleic acid of SEQ ID NO: 35. Claims 2 and 9-10 are withdrawn as they do not read on the elected species.
Status of Claims
Claims 1-3, 5-6, 8-10, 14-20 and 25-29 are pending; claims 2, 9-10, 16-20 and 25-29 are withdrawn; claims 1, 3, 5-6, 8 and 14-15 are being examined on the merits.
Claim Objections
Claims 3, 5-6, 8 and 14-15 objected to because of the following informalities: Claim 1 introduces the acronym “CAR” in reference to a “chimeric antigen receptor”; however, each of claims 3, 5-6, 8 and 14-15 recite a “chimeric antigen receptor” and do not use the acronym. If the acronym is introduced, it should be used thereafter for consistency. Appropriate correction is required.
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.
Claims 1, 3, 5-6, 8, 14, and 15 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.
Claim 1 recites an antibody domain having an antibody-binding portion of a polypeptide with a sequence selected from the group consisting of SEQ ID NOs: 12, 16, 19, 22, 25, 28 and 31. It is unclear what the “antibody-binding portion” of an undefined amino acid sequence is. The skilled artisan would not have a clear definition of which polypeptide “portions” would infringe upon the claim because the antibody-binding amino acid residues are not defined within the larger polypeptide. It is unclear if only the amino acid residues that contact an antibody are required, or if the antibody-binding portion is a reference to, for example, an extracellular domain of a structure defined by the polypeptide sequence. Thus, the limits of the required sequence of the binding domain of the CAR is unclear. As the metes and bounds of the claim are unclear, claim 1 is rejected for indefiniteness. As claims 3, 5-6 and 8 depend from claim 1, but fail to explicitly define the “portion sequence” that is the antibody-binding domain of the CAR, those claims are also rejected for indefiniteness.
Claims 1, 3, 5-6, 8, 14, and 15 recite amino acid sequences “having” a SEQ ID NO or an amino acid sequence that “has” a SEQ ID NO. It is unclear whether the terms “having” or “has” mean “comprising” or “consisting of” or “consisting essentially of.” As such the metes and bounds of the claims are unclear. Applicant is suggested to amend the claims to recite “comprising” or “consisting of” or “consisting essentially of” language.
Regarding claim 6, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Specifically, it is unclear if claim requires that the second signaling domain is distinct from the first signaling domain, or what makes them distinct from each other. As the metes and bounds of the claim is unclear, claim 6 is rejected for indefiniteness.
Claim Rejections - 35 USC § 102
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 1 and 3 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Hwang et al., (US 2019/0336533; published 11/7/2019).
Claims 1, 3, 5-6, 8 and 14-15 are drawn to a chimeric antigen receptor (CAR) comprising and extracellular domain of CD16, which binds to an antibody Fc region, a transmembrane domain (TM) of human CD28, and an intracellular signaling domain (ICD) of FcεRIγ. In the elected instant embodiment of the CAR, the CD16 extracellular domain is derived from the CD16 polypeptide of SEQ ID NO: 12, specifically amino acids 1-206 of SEQ ID NO: 12; the TM domain is SEQ ID NO: 5, and the ICD signaling domain is SEQ ID NO: 1. Thus the amino acid sequence of the CAR construct of instant claim 14 (SEQ ID NO: 36), is the combination of SEQ ID NO: 12 (residues 1-206) + SEQ ID NO: 5 + SEQ ID NO: 1.
Regarding claims 1 and 3; Hwang et al. teaches CARs and natural killer (NK) cells expressing the CARs (abstract). Hwang teaches the CAR may include an Fc receptor as the extracellular domain and thus may be used to associate with different antibodies depending on cell types of cancer to be treated; the Fc receptor may be any one selected from CD16, CD32, CD64, CD23 and CD89; and specifically, may be the whole or portion of the CD16 V158 variant (pg. 4, para. 0077). Hwang teaches the TM domain may include the whole of a portion of CD8α or CD28 (pg. 4, para. 0080). Hwang teaches the CAR may comprise one or more intracellular signaling domains, linked in various orders, and which may include the whole, of portions of, well known ICs such as OX40, CD28, 4-1BB or CD3zeta (pg. 4, para. 0083; pg. 5, para. 0084). Specifically, Hwang teaches the CD16V amino acid sequence of SEQ ID NO: 5 (pg. 9, Table 2) which is 100% identical to the first 206 amino acids of instant SEQ ID NO: 12, as well as the first 206 amino acids of the full embodiment of the CAR of instant SEQ ID NO: 36. Hwang teaches the CD28 TM domain sequence of SEQ ID NO: 11, which comprises the amino acid sequence of instant SEQ ID NO: 5 with 100% sequence identity. Hwang teaches various embodiments of a CAR comprising the CD16V ECD, a CD28 TM and 2-3 alternative IC signaling domains (see Table 1, pg. 7). Thus, each of the embodiments of the CAR of Hwang SEQ ID NOs: 33, 41, 43, 45, 47, 49 and 51 (see Table 2, pg. 9; pg. 86, claim 60), which comprise the “CD16V-28” ECD-TM domains, also comprise the ECD (i.e. antibody-binding portion) of the first 206 amino acids of instant SEQ ID NO: 12, as well as the TM of instant SEQ ID NO: 5; or together, the ECD-TM portions (amino acids 1-234) of CAR of instant SEQ ID NO: 36.
Thus, the CAR constructs of Hwang et al. comprise the ECD and TM domains of instant SEQ ID NOs: 12 (re. claim 1) and 5 (re. claim 3), respectively, and include one or more ICD signaling domains. Thus the CAR constructs of Hwang anticipate that of instant claims 1 and 3.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, 5-6, 8 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hwang et al., (US 2019/0336533; published 11/7/2019) and Patakas et al., (US 2020/0289564; published 9/17/2020) .
Claims 1, 3, 5-6, 8 and 14-15 are drawn to a chimeric antigen receptor (CAR) comprising and extracellular domain of CD16, which binds to an antibody Fc region, a transmembrane domain (TM) of human CD28, and an intracellular signaling domain (IC) of FcεRIγ. In the elected instant embodiment of the CAR, the CD16 extracellular domain is derived from the CD16 polypeptide of SEQ ID NO: 12, specifically amino acids 1-206 of SEQ ID NO: 12; the TM domain is SEQ ID NO: 5, and the IC signaling domain is SEQ ID NO: 1. Thus the amino acid sequence of the CAR construct of instant claim 14 (SEQ ID NO: 36) is the combination of SEQ ID NO: 12 (residues 1-206) + SEQ ID NO: 5 + SEQ ID NO: 1.
Hwang et al. teaches CAR constructs comprising a CD16 ECD (i.e. the antibody binding portion of instant SEQ ID NO: 12) and the CD28 TM domain of instant SEQ ID NO: 5, as described above. However, the CAR constructs of Hwang do not comprise the IC signaling domain of instant SEQ ID NO: 1.
Patakas et al. teaches modified CAR T cells, including gamma-delta T cells or NK cells, which express a CAR incorporating the signaling domain of a FCγ receptor (abstract). Patakas teaches CAR constructs comprise a cancer antigen specific scFv ECD, and further comprise a CD28 TM domain and a Fcγ common chain activation domain (Figure 1). Patakas teaches that common CAR constructs utilize similar signaling domains as alpha beta T cells; however, the effector functions of gamma-delta T cells and NK cells are unlike alpha beta T cells, and instead are linked to molecules such as FcγRs. Thus, the inventors determined that gamma delta T cells or NK cells expressing a CAR that includes stimulatory domains of Fcγ receptor common chain will result in increased effector functions (pgs. 1-2, paras. 0007-0008). Patakas teaches the CARs may comprise an intracellular signaling domain of SEQ ID NO: 1 or functional variants or fragments thereof (pg. 2, para. 0017). Patakas SEQ ID NO: 1 comprises the amino acid sequence of instant SEQ ID NO: 1 with 100% sequence identity; specifically the last 41 amino acids of Patakas SEQ ID NO: 1 are identical to instant SEQ ID NO: 1. Patakas teaches a CAR construct comprising an anti-CD19 scFv ECD, a CD28 TM domain and a Fcγ receptor IC signaling domain, of SEQ ID NO: 5 (pg. 4, para. 0044). Patakas SEQ ID NO: 5 comprises the CD28 TM domain of instant SEQ ID NO: 5 and the Fcγ receptor IC signaling domain of instant SEQ ID NO: 1, with 100% amino acid sequence identity, with no gaps or inserts. That is, the last 69 amino acids of Patakas SEQ ID NO: 5 are the combination of instant SEQ ID NO: 5 (TM) + SEQ ID NO: 1 (ICD) exactly. Thus, the CAR constructs of Patakas et al. comprise the TM-IC signaling domains of instant SEQ ID NOs: 5 and 1, respectively.
It would have been obvious to one of skill in the art to modify the CAR constructs comprising a CD16V ECD and CD28 TM domain, of Hwang et al., to comprise a Fcγ receptor IC signaling domain, of Patakas et al. One would have been motivated to do so given that expression of CAR constructs in NK cells, whereby the intracellular signaling domain is a Fcγ receptor IC signaling domain imparts increased effector functions to the CAR-expressing NK cells. There would have been a reasonable expectation for success given that the CD16V ECD is taught with 100% identity in a CAR construct by Hwang et al., the FcγR ICD is taught with 100% identity in a CAR construct by Patakas et al., and both Hwang and Patakas teach the CAR constructs comprise the CD28 TM domain with 100% identity, and both Hwang and Patakas teach the CAR constructs for expression in NK cells. Thus, the invention as a whole was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding instant claims 1, 3, 5-6, 8 and 14-15. The combination CAR of Hwang and Patakas comprises a CD16V antibody-binding portion as the ECD, a CD28 TM domain and a FcγR ICD; whereby the CD16V ECD comprises the antibody-binding portion of instant SEQ ID NO: 12, the TM comprises instant SEQ ID NO: 5 and the ICD comprises instant SEQ ID NO: 1 with 100% identity. Further, the combination CAR of Hwang and Patakas encodes the CAR of instant SEQ ID NO: 36 with 100% sequence identity. Thus the combination CAR of Hwang and Patakas make obvious the CAR of instant claims 1, 3, 5, 8 and 14, as well as the nucleic acid sequence encoding the CAR of instant SEQ ID NO: 35, of claim 15. Regarding claim 6, Patakas teaches the CAR may comprise one or more Fcγ receptor signaling domains (pg. 21, claim 1); and thus makes obvious instant claim 6.
Conclusion
No claims are allowed.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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