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 .
DETAILED ACTION
This application is in response to the papers filed on September 30, 2025. Claims 1-3, 5-6, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 81-82, 88, 92-94, 107-108, 116 and 121-122 are currently pending of which claims 3, 5, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 81-82, 92-94, 107, 116, and 121-122 have been amended, and claims 4, 7, 10-13, 16-33, 35-40, 43-52, 55-64, 66-68, 71-80, 83-87, 89-91, 95-106, 109-115, 117-120, and 123-125 have been cancelled in Applicant’s amendment filed on October 5, 2022.
Applicant’s election without traverse of the invention of Group I, e.g., claims 1-3, 5-6, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 82 and 93-94, drawn to a polynucleotide, a recombinant vector encoding said polynucleotide, and an isolated host cell comprising said recombinant vector, in the reply filed on September 30, 2025 in response to the restriction requirement filed on September 10, 2025 is acknowledged.
Claims 81, 88, 92, 107-108, 116 and 121-122 are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution. The requirement for restriction between Groups I-VIII is maintained for reasons of record, and hereby made FINAL. Applicant timely responded to the restriction (election) requirement in the paper filed on September 30, 2025.
Therefore, claims 1-3, 5-6, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 82 and 93-94 are currently /TERESA E KNIGHT/Primary Examiner, Art Unit 1634 under examination to which the following grounds of rejection are applicable
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No. PCT/US2021/025932, filed on April 6, 2021. Applicant’s claim for the benefit of a prior-filed parent provisional application 63/005,824 filed on April 6, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is April 6, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 5, 2022 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being 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)(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 1 is rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by Novartis. (US-2016/0340406-A1).
Regarding Claim 1, Novartis teaches a polynucleotide (“Accordingly, in one aspect, the invention provides a T cell comprising nucleic acid, e.g., exogenous nucleic acid” (par 0006)) encoding a) a 4-1 BB ligand (4-1 BBL) or a functional portion thereof (“(b) the nucleic acid comprises a second nucleic acid sequence encoding a polypeptide which enhances T cell priming,” (par 0008); “In an embodiment, the costimulatory molecule ETP is selected from the group consisting of ... CD137L (4-1BBL)” (par 0028)), and b) a chimeric antigen receptor (CAR) comprising an extracellular target-binding domain comprising a B7-H3-binding moiety, a transmembrane domain and a cytoplasmic domain comprising a signaling domain (“(a) the nucleic acid comprises a first nucleic acid sequence encoding a chimeric antigen receptor (CAR) comprising an extracellular domain, a transmembrane domain, and an intracellular signaling domain,” (par 0007); Accordingly, the present invention provides CARs that target the following cancer associated antigens (tumor antigens): ... B7H3, (par 0170)).
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.
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.
Claims 1-3, 5-6, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 82 and 93-94 are rejected under 35 U.S.C. 103 as being unpatentable over Mackall et al. (US 10,562,952 B2) in view of Ma et al. (US 2018/0162939 A1).
Claim 1 is directed to a polynucleotide encoding a 4-1BB ligand ( 4-lBBL) or a functional portion thereof, and a chimeric antigen receptor (CAR) comprising an extracellular target-binding domain comprising a B7-H3-binding moiety, a transmembrane domain and a cytoplasmic domain comprising a signaling domain.
Mackall teaches a CAR comprising an extracellular target-binding domain comprising a B7-H3-binding moiety (“The CARs of the invention have antigen specificity for CD276 (also known as B7-H3)” (col 5, par 2)), a transmembrane domain (“In an embodiment of the invention, the CAR comprises a transmembrane (TM) domain.” (col 6, par 6)) and a cytoplasmic domain comprising a signaling domain (“In an embodiment of the invention, the CAR comprises an intracellular T cell signaling domain.” (col, par 2)).
Mackall does not teach a polynucleotide encoding a 4-1BB ligand (4-1BBL) or a functional portion thereof.
Ma teaches a polynucleotide that encodes a CAR construct with a 4-1BBL (CD137L) enhancer linked by a P2A peptide, further stating , “Upon cleavage of this P2A peptide, A CAR construct with 4-1BBL splits to a CAR polypeptide and the full length of 4-1BBL protein… 4-1BBL provides a synergistic effect of T cell activation or anti-tumor activity with CD28 or 4-1BB. CAR is more powerful when equipped with 4-1BBL.” (par 0366).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the nucleotide that encodes a CAR as taught by Mackall et al. to further include a nucleotide sequence encoding 4-1BBL as taught by Ma because it would have been obvious to combine prior art elements according to known methods to yield predictable results. The CAR taught by Mackall includes an extracellular target-binding domain comprising a B7-H3-binding moiety, but lacks a sequence for 4-1BBL, but by incorporating this sequence there is a reasonable expectation there would an increased T cell activation or anti-cancer activity as described by Ma when using the 4-1BBL enhancer.
Regarding claim 2, dependent on claim 1, Ma teaches wherein the functional portion of 4-1BBL comprises an ectodomain of the 4-1BBL as seen in the claim 1 rejection because the enhancer is the full length of the polypeptide.
Regarding claim 3, dependent on claim 1, Ma teaches wherein the 4-1BBL comprises the amino acid sequence of SEQ ID NO: 1 as seen in the STIC sequence search provided wherein the sequence alignment is 100% for Result #6 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image1.png
1035
701
media_image1.png
Greyscale
Regarding claims 5 and 6, both dependent on claim 1, Mackall teaches wherein the B7-H3-binding moiety is an anti-B7-H3 single chain variable fragment (scFv), and furthermore, wherein the anti-B7-H3 scFv is derived from antibodies MGA271, 376.96, 8H9, or humanized 8H9 (“The antigen binding domain may comprise any antigen binding portion of the MGA271 antibody. For example, the antigen binding domain may be a… single-chain variable region fragment (scFv). In a preferred embodiment, the antigen binding domain is an scFv.” (col 5, par 5)).
Regarding claim 8, dependent on claim 5, Mackall teaches wherein the anti-B7-H3 scFv comprises a heavy chain variable region (VH) comprising an amino acid sequence of SEQ ID NO: 5 as seen in the STIC sequence search provided below in which the sequence alignment is 100% for Result #4 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image2.png
871
638
media_image2.png
Greyscale
Regarding claim 9, dependent on claim 8, Mackall teaches wherein the polynucleotide comprises a nucleotide sequence encoding the anti-B7-H3 heavy chain variable region (VH) comprising the nucleotide sequence of SEQ ID NO: 6, or a nucleotide sequence having at least 80% sequence identity thereof as seen in the STIC sequence search provided below in which the sequence alignment is 89% for Result #1 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image3.png
122
813
media_image3.png
Greyscale
Regarding claim 14, dependent on claim 5, Mackall teaches wherein the anti-B7-H3 scFv comprises the amino acid sequence of SEQ ID NO: 27 as seen in the STIC sequence search provided below in which the sequence alignment is 100% for Result #1 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image4.png
104
775
media_image4.png
Greyscale
Regarding claim 15, dependent on claim 14, Mackall teaches wherein the polynucleotide comprises a nucleotide sequence encoding the anti-B7-H3 scFv comprising the nucleotide sequence of SEQ ID NO: 28, or a nucleotide sequence having at least 80% sequence identity thereof as seen in the STIC sequence search provided below in which the sequence alignment is 87% for Result #1 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image5.png
97
776
media_image5.png
Greyscale
Regarding claim 34, dependent on clam 1, Mackall teaches wherein the transmembrane domain is derived from CD8 or CD28 (col 6, ln 62-66) and the signaling domain is derived from CD3ζ (col 7).
Regarding claim 41, dependent on claim 1, Ma teaches wherein the extracellular target-binding domain further comprises a hinge domain between the single-chain variable fragment (scFv) region and the transmembrane domain (Fig. 96A; par 0178).
Regarding claim 42, dependent on claim 41, Ma teaches wherein the hinge domain is derived from CD8a stalk, CD28 or IgG1 (par 0261-0263).
Regarding claims 53 and 54, both dependent on claim 1, Mackall teaches wherein the cytoplasmic domain further comprises one or more costimulatory domains, and wherein the one or more costimulatory domains are derived from CD28, 4-1BB, CD27, CD40, CD134, CD226, CD79A, ICOS, or MyD88, or any combination thereof (“In an embodiment of the invention, the CAR comprises an intracellular T cell signaling domain. The intracellular T cell signaling domain may comprise an intracellular T cell signaling domain of any one or more of CD28, 4-1 BB, and CD3 zeta (ζ).” (col 7, par 2)). Moreover, Ma teaches “CAR also has costimulatory domain (including, but not limited to, CD28 or 4-1BB) and intracellular signaling, CD3 zeta chain while 4-1BBL does not bear these components.” (par 0178).
Regarding claim 65, dependent on claim 1, Mackall teaches wherein the CAR comprises the amino acid sequence of any of SEQ ID NOs: 41, 43, or an amino acid sequence having at least 80% sequence identity thereof as seen in the STIC sequence search provided below in which the sequence alignment is around 87% for Result to instant SEQ ID NO: 41, and respectively around 95% for instant SEQ DI NO: 43 (A longer version of the STIC Search will be provided in the Office Action).
PNG
media_image6.png
125
774
media_image6.png
Greyscale
PNG
media_image7.png
111
772
media_image7.png
Greyscale
Regarding claims 69 and 70, both dependent on 1, Ma teaches wherein the sequence encoding the 4-lBBL or a functional portion thereof is operably linked to the sequence encoding the CAR via a sequence encoding a self-cleaving peptide and/or an internal ribosomal entry site (IRES) (Figure 96A (“P2A”), par 0178; par 0440, 01172).
Regarding claim 82, 93 and 94, all dependent on claim 1, the rejection to claim 1 above is applied herein. In particular, Mackall states, “Further embodiments of the invention provide related nucleic acids, recombinant expression vectors, host cells,” (col 1).
Conclusion
Claims 1-3, 5-6, 8-9, 14-15, 34, 41-42, 53-54, 65, 69-70, 82 and 93-94 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634