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 with traverse of Group I, claims 1-2, and 4-28 in the reply filed on November 14, 2025 is acknowledged. The traversal is on the ground(s) that there would not be a serious burden on the Examiner if all the species of the pending claims were searched together and to examine all the claims together. This is not found persuasive because there was not a species election requirement in the restriction mailed on September 16, 2025. Examiner also notes that the claims were restricted due to lack of unity of invention, because the special technical feature was disclosed in the prior art as discussed in the Office action below.
Claims 1, 4, 5, 7-28 are under examination in this Office action. Claims 29-31, and 35 are withdrawn as being drawn to non-elected invention.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 11, 2022, November 3, 2023, April 12, 2024, June 4, 2024 and November 19, 2024 have been considered by the examiner.
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)(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, 4, and 8 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kim et al. (WO2016/054520).
Kim et al. teach effector cells expressing engineered cell surface protein comprising extracellular domain comprising CD3 fusion protein and a bispecific T cell activating element comprising a tumor antigen recognition region, a CD3 epitope, a transmembrane domain, an intracellular domain, comprising a sequence of an intracellular signaling protein, wherein the engineered cell surface protein is engineered by combining the CD3 epitope with a protein other than CD3 and wherein the CD3 is CD3 epsilon domain, costimulatory domain 4IBB signaling domain, CD28 signaling domain, ICOS signaling domain, CD30 signaling domain, NKG2D signaling domain (see claims 1-118, page 2, paragraph [004], page 3, paragraph [005], page 4, paragraph [006], page 7, paragraph [011], page 32 paragraph [068], page 55, paragraph [0125], paragraphs [0146-0147] and Figures 1-6).
Thus, by this disclosure Kim et al. anticipate the present claims.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 4, 5, 7-28 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (WO2016/054520) in alternative with Huehls et al. (Immunology and Cell Biology, 2015, p. 290-296) in view of June et al. (US Patent 9,499,629), and further in view of Kodandapani et al. (US Patent 9,683,985), Sadelain et al. (US Patent 7,446,190) and Miao et al. (US Patent Application Publication US 2023/0002503).
Regarding present claims 1, 4, 5, 8, and 11. Kim et al. teach effector cells expressing engineered cell surface protein comprising extracellular domain comprising a CD3 epitope, a transmembrane domain, an intracellular domain, comprising a sequence of an intracellular signaling protein, wherein the engineered cell surface protein is engineered by combining the CD3 epitope with a protein other than CD3 and wherein the CD3 is CD3 epsilon domain, costimulatory domain 4IBB signaling domain, CD28 signaling domain, ICOS signaling domain, CD30 signaling domain, NKG2D signaling domain (see claims 1-118, page 2, paragraph [004], page 3, paragraph [005], page 4, paragraph [006], page 7, paragraph [011], page 32 paragraph [068], page 55, paragraph [0125] and Figures 1-6). Kim et al. teaches effector cells with engineered CD3e expression and bispecific T cell engager (BiTE) (see Figure 4).
Regarding present claims 1, 4-5, 12-14, 17, 18. Huehls et al. teach Bispecific T cell engagers comprising HER2 tumor antigen recognition region (see page 8 and Figures 1-2). Huehls et al. teach that BiTEs, enhance the patient’s immune response to tumors by retargeting T cells to tumor cells and are constructed of two single chain variable fragments (scFv) connected in tandem by a flexible linker (see pages 4-8). Huehls et al. teach that scFv binds to a T cell-specific molecule, usually CD3, while the second scFv binds to a tumor-associated antigen and specificity allows a BiTE to physically link a T cell to a tumor cell, ultimately stimulating T cell activation, tumor killing and cytokine production (see Abstract).
Regarding present claims 1 and 21-28. Kim et al. teaches a pharmaceutical composition comprising a pharmaceutically acceptable carrier, vector comprising the nucleic acid comprising the cell surface protein comprising extracellular domain comprising a CD3 epitope, a transmembrane domain, an intracellular domain, comprising a sequence of an intracellular signaling protein, wherein the engineered cell surface protein is engineered by combining the CD3 epitope with a protein other than CD3 and wherein the CD3 is CD3 epsilon domain, costimulatory domain 4IBB signaling domain, CD28 signaling domain, ICOS signaling domain, CD30 signaling domain, NKG2D signaling domain (see Example in paragraphs [0170-0177]. The ration of claim 27 would have been a routine optimization that a skilled artisan can readily perform.
Regarding present claims 8 and 9. June et al. teach 4-1BB-derived costimulatory signal molecule identical with present SEQ ID NO: 10 (see SEQ ID NO: 58 in June et al.). June et al. teach a method of treating a human having a disease, disorder or condition associated with an elevated expression of a tumor antigen, the method comprising administering to the human an effective amount of a cell genetically modified to express a CAR wherein the CAR comprises a CD19 antigen binding domain, a transmembrane domain, a costimulatory signaling region comprising 4-1BB, and a CD3 zeta signaling domain (see claims 1-15).
Present SEQ ID NO: 10 and SEQ ID NO: 23 in June et al.
Query Match 100.0%; Score 232; Length 42;
Best Local Similarity 100.0%;
Matches 42; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
||||||||||||||||||||||||||||||||||||||||||
Db 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
Regarding present claim 7. Kodandapani et al., teach an antibody fragmentCD3 epsilon chain domain having a sequence identical with present SEQ ID NO: 4 (see SEQ ID NO: 58 in Kodandapani and a sequence alignment below).
Present SEQ ID NO: 4 and SEQ ID NO: 53 in Kodandapani et al.
Query Match 100.0%; Score 572; Length 104;
Best Local Similarity 100.0%;
Matches 104; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHL 60
Qy 61 SLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMD 104
||||||||||||||||||||||||||||||||||||||||||||
Db 61 SLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMD 104
Regarding present claim 10. Sadelain et al. teach nucleic acids encoding chimeric T cell receptors comprising a cytoplasmic signaling CD3 zeta, sequence identical with present SEQ ID NO: 12 (see SEQ ID NO: 14 in Sadelain et al. and sequence alignment below).
Present SEQ ID NO: 12 and SEQ ID NO: 14 in Sadelain).
Query Match 100.0%; Score 593; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
Qy 61 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
Regarding present claims 14 and 15. Miao et al. teach tumor antigen recognition region H-YE-232 identical with present SEQ ID NO: 18 (see SEQ ID NO: 19 in Miao and sequence alignment below) and teaches CAIX target tumor antigen (see Example 4).
Present SEQ ID NO: 18 and SEQ ID NO: 19 in Miao).
Query Match 100.0%; Score 602; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQESGGGLVQPGGSLRLSCAASGNSANIFSFASVAWYRQAPGKQRELVAVITSAGGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQESGGGLVQPGGSLRLSCAASGNSANIFSFASVAWYRQAPGKQRELVAVITSAGGT 60
Qy 61 KYSDSVKGRFTISRDNAKNTILLQMNSLKPEDTAVYYCNVDYLQDYWGQGTQVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KYSDSVKGRFTISRDNAKNTILLQMNSLKPEDTAVYYCNVDYLQDYWGQGTQVTVSS 117
It would have been prima facie obvious to provide a nucleic acid molecule of either Kim and/or Huehls, comprising the fusion protein of present formula I and comprising the T cell activating element of present formula II, wherein the CD3e and the T cell activating element are expressed in a single cell, because Huehls teaches expressing both, the CD3 and the T cell activating element in a single cell for the purpose of simultaneous binding to T cell and to the tumor cell (see Figure 2 in Huehls).
It would have been prima facie obvious to provide a nucleic acid molecule of either Kim and Huehls, further comprising June’s 4-1BB-derived costimulatory signal molecule identical with present SEQ ID NO: 10, because June teaches that 4-1BB costimulatory molecule expressed together with anti-CD19 CAR including both CD3-zeta undergo a robust in vivo T cell expansion and can establish CD19-specific memory cells that persist at high levels for an extended amount of time in blood and bone marrow (see column 10).
It would have been prima facie obvious to provide a nucleic acid molecule of either Kim and Huehls, further comprising Kodandapani et al. antibody fragment CD3 epsilon chain domain having a sequence identical with present SEQ ID NO: 4 because Kodandapani et al. teaches CD3 epsilon as a surrogate target for cancer therapeutics (see under Assay and Detect Binding in column 55).
It would have been prima facie obvious to provide a nucleic acid molecule of either Kim and Huehls, further comprising Sadelain et al. chimeric T cell receptors comprising a cytoplasmic signaling CD3 zeta, comprising a sequence identical with present SEQ ID NO: 12 because Sadelain et al. teaches that CD3 zeta cytoplasmic domain, delivers a potent signal in the absence of the remaining components of the TCR-CD3 complex and is well suited for activating cytolytic functions (see column 5).
It would have been prima facie obvious to provide a nucleic acid molecule of either Kim and Huehls, further comprising Miao et al. tumor antigen recognition region H-YE-232 identical with present SEQ ID NO: 18, because Miao teaches that the SEQ ID NO: 18 binds CAIX tumor antigen (see Example 5).
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Claims Objection
Claim 16, 17 and 20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
SEQ ID NO: 65, 66, 67 and 73 are free of prior art.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648