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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/12/2025 has been entered.
Claim Status
Claims 5, 9, 11, 17-18, 22, 27-28, 36, and 44 are cancelled. Claims 1-4, 6-8, 10, 12-16, 19-21, 23-26, 29-35, 37-43, and 45-46 as filed on 12 July 2025 are pending and under examination.
Rejections Withdrawn
Rejection of claims 13-14 under 35 U.S.C. 112(b) is withdrawn with amendment of claims.
Applicant’s arguments, see rejection under 35 USC 103, filed 07/12/2025, with respect to the teaching of the sequence have been fully considered and are persuasive. The rejection of claims 1-4, 6-8, 10, 12, 15-16, 19-21, 23-26, 29-35, 37-43, and 45-46 has been withdrawn. New rejections have been made below with New Art so no response to arguments related to previous art rejections.
Rejection of claims 1-2, 4, 6-8, 10, 12, 15, 19-21, 23-26, 29-35, 37-43, and 45-46 under 35 U.S.C. 112(a) is withdrawn with amendment of claims.
New Rejections
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 1-4, 6-8, 10, 12-16, 19-21, 23-26, 29-35, 37-38, 43, and 45-46 are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107082813 A) (PTO-892) and Shiku (US 9175308 B2) (PTO-892).
Dong as attached is a combination of 3 files: a machine translated copy of the document, a Chinese copy of the original document, and a human translated copy of Figure 2. All were used in the rejection.
Sequences:
Instant SEQ ID NO: 12 the PD-L1 ligand is taught in Dong’s SEQ ID NO: 1 starting in page 10 in the second to last line to page 12 second line of the untranslated document.
Dong teaches SEQ ID NO: 3 on pages 12-13 of untranslated document that matches the CD8 alpha hinge sequence of instant SEQ ID NO: 13 required by claims 1-3, and 6.
Dong teaches SEQ ID NO: 5 ([0005] and page 13 of untranslated document) which matches instant SEQ ID NO: 21 which is 4-1BB intracellular domain as required by claims 1-3 part c, 10, and 12.
Regarding claims 1-4, Dong teaches a chimeric antigen receptor comprising an extracellular region peptide, a transmembrane peptide, and an intracellular domain and further teaches the extracellular region peptide comprises an anti-PD-1 scFv, a joining peptide, and the PD-L1 extracellular region (abstract and claim 1). Dong further teaches the transmembrane domain is a CD28 transmembrane domain or CD8 transmembrane domain and a CD8 hinge (claim 2). Dong further teaches the intracellular domain is selected from 4-1BB, CD28, or CD3 zeta (claim 3).
Regarding the sequence of claim 4, Dong teaches CD8 alpha in the extracellular segment in Figure 2 (untranslated document page 1 and translated figure added to the end of the document). Further instant SEQ ID NO: 14 and 15 are within the sequence of PD-L1 so Dong by teaching instant SEQ ID NO: 12 in the extracellular domain teaches instant SEQ ID NO: 14 and 15.
Regarding claims 15, 19-21, and 23-26, Dong teaches a vector comprising a nucleic acid sequence that encodes the chimeric antigen receptor (claims 6-7) and further teaches a cell comprising that vector including T cell or NK cell (claims 9-10) and teaches the use of autologous cells which would be from humans (page 5 in last line onto page 5 in par 1-4).
Regarding claims 29 and 31, Dong teaches the administration of the recombinant cells to mice by tail vein this would inherently be in a pharmaceutical composition (page 7 under “Anti-Tumor Activity”).
Regarding claims 30 and 32, the amounts recited would necessarily be present as the cells are expressing the chimeric antigen receptor of their invention.
Regarding claims 33-35, Dong teaches the isolation of autologous cells from a patient and the transfection of these isolated cells to produce the chimeric antigen receptor of Dong including the cell culture to expand said isolated and transformed cells (page 4 in last 4 lines, all of page 5 and page 6 to par 8).
Regarding claims 37-38, Dong teaches a vector comprising a nucleic acid sequence that encodes the chimeric antigen receptor (claims 6-7) and further teaches a cell comprising that vector including T cell or NK cell (claims 9-10) and teaches the use of autologous cells which would be from humans (page 5 in last line onto page 5 in par 1-4).
Regarding claims 39, 42-43, and 45, Dong teaches the anti-tumor activity against glioblastoma U251 cells and study in a mouse where administrations is by tail vein which would be intravenous(page 7 in par 7-8)
Dong does not teach the CD28 transmembrane domain of SEQ ID NO: 16 or 17 with 0 to 3 substitutions in the sequences. Dong does not teach the decreasing of TFH cells of CD4 T cells in an animal model.
This deficiency is filled by Shiku.
Shiku teaches the CD28 transmembrane domain for use in a chimeric antigen receptor of SEQ ID NO: 39 which matches instant SEQ ID NO: 17 (Abstract and col 57-60). This is with a CD8 hinge (Figure 1). Shiku teaches multiple equivalent transmembrane domains including CD28, CD8 and others (col 8 in lines 43-60).
It would have been obvious at the time the application was filed to substitute the CD28 transmembrane domain of the chimeric antigen receptor of Dong with the CD28 transmembrane domain of Shiku to arrive at the fusion protein of the instant claims. Dong and Shiku are teaching chimeric antigen receptors comprising CD28 transmembrane domains and both teach the substitution of transmembrane domains and that they are art equivalent for use in chimeric antigen receptor. Dong and Shiku teach the transmembrane domains as art equivalents making their substitution obvious and likely to succeed when substituted.
The combination of Dong and Shiku would render the fusion of instant SEQ ID NO: 32 obvious as they teach all of the elements of the sequence.
Regarding claim 45, as Dong and Shiku teach the administration of the cell of claim 24 to human and animals it would be expected that the biological effect of decreasing TFH and CD4 T cells would occur since the chimeric polypeptide administered have the same targets and therefore the biological effect would be the same.
Claims 1, 24, and 39-41 are rejected under 35 U.S.C. 103 as being unpatentable over Dong (CN 107082813 A) (PTO-892), Shiku (US 9175308 B2) (PTO-892), Sung (US 20170189476 A1) (PTO-892), and Gianchecchi et. al. Autoimmunity Reviews 12:1091-1100. (2013) (PTO-892).
The teachings of Dong from the previous art rejection are incorporated here in full.
Dong does not teach the CD28 transmembrane domain of SEQ ID NO: 16 or 17 with 0 to 3 substitutions in the sequences. Dong does not teach the treatment of systemic lupus erythematosus.
These deficiencies are filled by Shiku, Sung, and Gianchecchi.
The teachings of Shiku from the previous art rejection are incorporated here in full.
Sung teaches the use of a fusion proteins comprising the extracellular domain of PD-L1 in the treatment of autoimmune disease including systemic lupus erythematosus (abstract and [0138]). Sung teaches its fusion proteins comprise PD-L1 (Figure 17). Sung further teaches inhibition of T cell proliferation (Figures 24 and 28).
Gianchecchi teaches the use of PD-1/PD-L1 in controlling immune response in multiple autoimmune disease including insulin dependent diabetes, rheumatoid arthritis, and systemic lupus erythematosus (abstract).
It would have been obvious at the time the application was filed to combine the method of treating cancer with PD-1/PD-L1 modulation of Dong with its fusion protein with the method of treating autoimmune diseases including systemic lupus erythematosus taught by Sung. One of skill in the art would have been motivated by Sung and Gianchecchi to explore further applications of the chimeric antigen receptor of Dong. The chimeric antigen receptor of Dong is a fusion protein taught to act on PD-1/PD-L1 and be tolerated as a pharmaceutical, Sung and Gianchecchi teach modulation of PD-1/PD-L1 in the patient population of autoimmune disease in general and systemic lupus erythematosus specifically teaching a new potential new application for the fusion of Dong. There would have been a reasonable expectation of success as Sung teaches the use of a fusion protein comprising an extracellular domain of PD-L1 in the treatment of systemic lupus erythematosus and the fusion of Dong comprises an extracellular domain of PD-L1 which is a tolerated pharmaceutical.
Conclusion
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/F.E./ Examiner, Art Unit 1643
/Meera Natarajan/ Primary Examiner, Art Unit 1643