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
Election/Restrictions
1. Applicant’s election of Group I claims 1-11, 16, and 17 in the reply filed on December 15, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
2. Claims 1-20 are pending.
3. Claims 12-15 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
4. Claims 1-11, 16, and 17 are currently under consideration.
Priority
5. 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, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/391,566 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of July 24, 2023 for claims 1-3, 7-11, 16 and 17 because the claims as currently constituted recite i) a fusion protein, comprising at least one single chain antibody fragment (scFv), and a cancer antigen or marker, or a fragment thereof, wherein the scFv is capable of selectively binding to a cytokine released by chimeric antigen receptor (CAR) expressing cell, and wherein the cancer antigen or marker comprises extracellular domain of CD19 and ii) a fusion protein, comprising at least single chain antibody fragment (scFv), and a cancer antigen or marker, or a fragment thereof, wherein the scFv is capable of selectively binding to a cytokine released by an immunotherapy cell and a review of the parent Application does not reveal support for the claimed fusion proteins. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
Claims 4-6 have a priority date of July 22, 2022 based on the disclosure of Application No. 63/391,566.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
6. Claim 11 is 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 11 is drawn to the fusion protein of claim 9, wherein the fusion protein comprises the nucleotide sequence of SEQ ID NO: 14. Claim 11 is unclear and indefinite because it is unclear how the fusion protein can comprise the nucleotide sequence of SEQ ID NO: 14 or if claim 11 is drawn to a fusion protein or a nucleotide sequence encoding the fusion protein.
Amendment of claim 11 to, e.g., the fusion protein of claim 9, wherein the fusion protein is encoded by the nucleotide sequence comprising SEQ ID NO: 14, would help to obviate this rejection.
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.
7. Claim(s) 1-4, 7-9, 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over US 20201/0017271 A1 (Tan et al. Jan. 21, 2021, IDS), “Tan”, in view of US 2021/0079060 A1 (Lobb et al. Mar. 18, 2021), “Lobb” in view of US 2018/0044423 A1 (Ebersbach et al. Feb. 15, 2018, IDS), “Ebersbach”.
Tan teaches transgenic T cells expressing membrane-bound anti-IL6 (mb-aIL6) single chain variable fragment (scFv).
Tan teaches the transgenic T cells are useful for suppressing proliferation of IL-6-dependent cells, reducing IL-6 concentration, or both. In one embodiment, the vector is a bicistronic construct encoding the mb-aIL6 and an anti-CD19-41 BB-003ζ chimeric antigen receptor (CAR). In another embodiment, an anti-IL-6 scFv can be linked to a 41 BB and CD3ζ domains to form an anti-IL-6 CAR. The transgenic T cells expressing said constructs can reduce the risk of cytokine release syndrome (CRS) in cancer patients being treated with CAR T cell. See abstract and ¶¶ 007-0011 and claims 1-20.
Tan teaches that the scFv can also be directed to a wide variety of cytokines, such as IL-6 (e.g., anti-IL-6), (TNF)-α (e.g., anti-TNF-α), IL-1β (e.g., anti-IL-1β), IL-12 (e.g., anti-IL-12), IL-17 (e.g., anti-IL-17), IL-18 (e.g., anti-IL-18), IFNγ (e.g., anti-IFNγ), and others. See ¶¶ 0008, 0023, 0041, and 0044.
Tan teaches using linkers, like (Gly4Ser)3, for coupling the domains of the membrane-bound anti-cytokine constructs. See ¶¶ 0041-0043, 0053, 0056 and 0057.
Tan teaches as set forth above, but does not that the anti-cytokine scFv is fused to the extracellular domain of CD19.
Lobb teaches CD19 variants comprising the extracellular domain of CD19 that have the ability to bind anti-CD19 antibodies and improved stability. See abstract and ¶¶ 0003, 0021, 0032 and 0125-0130.
Lobb teaches fusion proteins of the CD19 variants and scFv antibodies. See ¶¶ 0010, 0039-0047 and 0163.
Lobb teaches killing of Her2, CD20, and EGFR positive cells by a CAR19 due to bridging by C-terminal scFv/ CD20, and EGFR -CD19 variant fusion proteins. See ¶¶ 0044, 0041, 0049, 0052, 0054, 0057 and 0058 and Examples 11-13, and 15.
Lobb teaches detecting C-terminal scFv/CD20, and EGFR -CD19 variant fusion proteins. See ¶¶ 0040-0042, and 0045. Examples 13 and 15.
Ebersbach teaches that CAR T cell activity can be regulated by having CAR cells express receptors like CD19 or their extracellular domains that can be targeted by antibodies that can eliminate the CAR cells by inducing antibody dependent cell-mediated cytotoxicity (ADCC) or compliment-induced cell death.. See ¶¶ 00486.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Tan, Lobb, and Ebersbach and fuse the CD19 extracellular domains of Lobb or Ebersbach to the anti-cytokine scFv constructs of Tan because Lobb teaches the CD19 extracellular domains have increased stability, can be detected by CD19 antibodies, and allow CD19 CAR cell directed killing. One would have been motivated to fuse the CD19 extracellular domains of Lobb or Ebersbach to the anti-cytokine scFv constructs of Tan to allow detection of the CD19 scFv fusion constructs and regulate CAR cell activity by targeting the CD19 extracellular to eliminate the CAR cells with an anti-CD19 antibody as taught by Ebersbach or anti-CD19 CAR T cells as taught by Lobb.
8. Claim(s) 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over US 20201/0017271 A1 (Tan et al. Jan. 21, 2021, IDS), “Tan”, in view of US 2021/0079060 A1 (Lobb et al. Mar. 18, 2021), “Lobb” in view of US 2018/0044423 A1 (Ebersbach et al. Feb. 15, 2018, IDS), “Ebersbach” as applied to claims 1-4, 7-9, 16 and 17 above, and further in view of WO 2023/201237 A1 (Brady et al. Oct. 19, 2023, effectively filed April 11, 2022), “Brady”.
Tan, Lobb, and Ebersbach teach as set forth above, but do not teach the anti-IFNg scFv of SEQ ID NO: 1 or the fusion proteins of SEQ ID NO: 3 or SEQ ID NO: 5.
Tan additionally teaches that the scFv can have the signal peptide of SEQ ID NO: 2, MALPVTALLLPLALLLHAARP, which is the signal peptide of the claimed SEQ ID NO: 5. See ¶ 0042 and p. 10-Sequences.
The CD19 SEQ ID NO: 2 of Lobb is comprised by the claimed SEQ ID NOs: 3 and 5. See Appendix.
Brady teaches macromolecules comprising a first binding domain linked to a second binding domain, wherein (a) the first binding domain specifically binds a disease signature ligand in a biological sample; and (b) the second binding domain specifically binds an effector ligand in the biological sample and induces a cellular effector function upon binding to the effector ligand. See p. 1-lines 14-17/
Brady teaches the disease signature ligand can be an IFNg which is bound by an scFv. See p. 2-lines 8-11 and paragraph bridging pp. 13-14 and Fig. 8A.
The IFNg scFv of Brady is SEQ ID NO: 5, which comprises the claimed SEQ ID NO: 1. See p. 53-Table 2, p. 55-line 37, and Appendix.
Brady teaches the IFNg scFv of SEQ ID NO: 5 effectively binds to IFNg. See Example 3A and Fig. 8.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Tan, Lobb, Ebersbach and Brady and use the IFNg scFv of SEQ ID NO: 5 of Brady in the CD19 scFv fusion constructs of Tan, Lobb, and Ebersbach linked by (Gly4Ser)3 linkers of Tan because Brady teaches the IFNg scFv of SEQ ID NO: 5 effectively binds to IFNg. One would have been motivated to use IFNg scFv of Brady in the CD19 scFv fusion constructs of Tan, Lobb, and Ebersbach given its effectiveness in binding IFNg.
Conclusion
9. Claims 1-9, 11, 16, and 17 are rejected. Claim 10 is 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.
No claims allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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, Janet L Epps-Smith can be reached at 571-272-0757. 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.
/PETER J REDDIG/ Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 1 with SEQ ID NO: 5 of Brady
ID BNW59418 standard; protein; 249 AA.
XX
AC BNW59418;
XX
DT 14-DEC-2023 (first entry)
XX
DE Anti-IFN gamma single chain antibody, SEQ ID 5.
XX
KW IFN-gamma; Interferon gamma ligand; cell cycle; single chain antibody;
KW therapeutic.
XX
OS Unidentified.
XX
CC PN WO2023201237-A1.
XX
CC PD 19-OCT-2023.
XX
CC PF 11-APR-2023; 2023WO-US065640.
XX
PR 11-APR-2022; 2022US-0329747P.
PR 11-APR-2022; 2022US-0329753P.
XX
CC PA (FLAG ) FLAGSHIP PIONEERING INNOVATIONS V INC.
XX
CC PI Brady JR, Yang SY, Mendlein JD;
XX
DR WPI; 2023-B0381P/090.
XX
CC PT New macromolecule comprising first binding domain linked to second
CC PT binding domain, which specifically binds disease signature ligand, and
CC PT effector ligand in biological sample, used e.g. to induce cellular
CC PT effector function in cell.
XX
CC PS Example 1; SEQ ID NO 5; 86pp; English.
XX
CC The present invention relates to a novel macromolecule. The macromolecule
CC comprising (i) a first binding domain linked to a second binding domain,
CC where (a) the first binding domain specifically binds a disease signature
CC ligand in a biological sample, and (b) the second binding domain
CC specifically binds an effector ligand in the biological sample and
CC induces a cellular effector function upon binding to the effector ligand,
CC the macromolecule is capable of forming a multimer in the presence of the
CC disease signature ligand, and induction of the effector function by the
CC macromolecule is conditional upon each member of the multimer binding the
CC disease signature ligand. The invention further discloses: (1) a pair of
CC macromolecules; (2) a nucleic acid encoding the macromolecule; (3) a pair
CC of nucleic acids encoding the pair of macromolecules; (4) a vector
CC comprising the nucleic acid; (5) a vector or pair of vectors comprising
CC the pair of nucleic acids; (6) a host cell comprising the nucleic acid or
CC pair of nucleic acids or the vector or pair of vectors; (7) a multimer
CC comprising either at least two of the macromolecule, or at least one copy
CC of each of the pair of macromolecules; (8) a macromolecule complex or
CC macromolecule or the nucleic acid or pair of nucleic acids; (9) a method
CC for modulating the state of a cell, or inducing a cellular effector
CC function in a cell; (10) a method for determining the state of a cell;
CC and (11) a method for inducing a cellular effector function in a cell.
CC The macromolecule, pair of macromolecules, nucleic acid, pair of nucleic
CC acids, vector or pair of vectors, host cell, multimer or macromolecule
CC complex is useful for modulating the state of a cell, or inducing a
CC cellular effector function in a cell, determining the state of a cell,
CC and treating disease.
XX
SQ Sequence 249 AA;
Query Match 100.0%; Score 1327; Length 249;
Best Local Similarity 100.0%;
Matches 249; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDGSSGWYVPHWFDPWGQGTLVT 120
Qy 121 VSSGGGGSGGGGSGGGGSNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSSGGGGSGGGGSGGGGSNFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPG 180
Qy 181 SSPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDGSNRWMF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SSPTTVIYEDNQRPSGVPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDGSNRWMF 240
Qy 241 GGGTKLTVL 249
|||||||||
Db 241 GGGTKLTVL 249
Alignment of SEQ ID NO: 3 with SEQ ID NO: 2 of Lobb
RESULT 1
AASEQ2_02032026_171744
Query Match 48.5%; Score 1424; DB 1; Length 272;
Best Local Similarity 100.0%;
Matches 260; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 286 PEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLA 345
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 PEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLA 60
Qy 346 IWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNR 405
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNR 120
Qy 406 SSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS 465
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS 180
Qy 466 CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKY 525
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKY 240
Qy 526 YCHRGNLTMSFHLEITARPV 545
||||||||||||||||||||
Db 241 YCHRGNLTMSFHLEITARPV 260
Alignment of SEQ ID NO: 5with SEQ ID NO: 2 of Lobb
RESULT 1
AASEQ2_02032026_171855
Query Match 50.2%; Score 1424; DB 1; Length 272;
Best Local Similarity 100.0%;
Matches 260; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 PEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLA 60
Qy 61 IWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNR 120
Qy 121 SSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLS 180
Qy 181 CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKY 240
Qy 241 YCHRGNLTMSFHLEITARPV 260
||||||||||||||||||||
Db 241 YCHRGNLTMSFHLEITARPV 260