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 .
The amendments of 05/12/2026 have been entered in full. Claims 1, 2, 4-8, 10, 12, 13, 16, 19-21, 23, 25-27, 30, and 32 are pending.
All prior objection/rejections not specifically maintained in this Office action are hereby withdrawn in view of Applicants’ amendment and/or arguments filed 05/12/2026.
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.
Claims 1, 2, 4-8, 10, 12, 13, 16, 19-21, 23, 25-27, 30, and 32 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.
As amended on 05/12/2026, claim 1 recites “wherein the scFv antibody comprises a heavy chain variable (VL) domain….and a light chain variable (VH) domain comprising…” That is, the amendments intended to o correctly identify SEQ ID NO:1 as corresponding to the VL sequence and SEQ ID NO:2 as corresponding to the VH sequence changed the abbreviations but not the words describing the domains, resulting in a conflict. The remaining claims are unclear as they depend from claim 1.
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.
Claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 20, 21, 23, 25-27, 30, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180186878 (Rosenthal; of record) taken together with US 20150050729 (June).
The pending claims are drawn to a chimeric antigen receptor (CAR) nucleic acid construct, comprising sequences encoding a signal peptide, an scFV comprising variable heavy and light antibody domains specific for CD19, a hinge region, a transmembrane domain, and intracellular domains derived from the intracellular domains of CD28 and CD3-ζ. In claim 1, the scFv comprises a light chain variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:1 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:2. Claim 32 recites an embodiment wherein the VL domain comprises SEQ ID NO:1. The scFv comprising both antibody domains and a peptide linker is further defined in claim 4 as comprising the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence having at least 95% identity to SEQ ID NO:12.
Rosenthal discloses a CAR comprising signal, anti-CD19scFV, hinge, transmembrane, CD28 and CD3-ζ components ([0295] SEQ ID NO:21). The signal peptides are generic in both Rosenthal and pending claim 8. SEQ ID NO:21 of Rosenthal comprises 100% identity to SEQ ID NOs 1, 3, 6, 7, 8, and 99.1% identity to SEQ ID NO:2, differing from SEQ ID NO:2 by the conservative substitutions of TT for SS at the carboxyl terminus. These two substitutions are the only differences between the complete scFv of the present claims (SEQ ID NO:12; claim 4) and that of Rosenthal (SEQ ID NO:21). One of skill in the art would not expect the conservative substitutions of SS for TT at the carboxyl terminus of the VH domain would have functional consequences for the construct. The instant specification does not assert any functional significance for the final two amino acids of the VH domain.
Furthermore, scFvs having SS, as in SEQ ID NO: 2 and SEQ ID NO: 12, are well known in the art and have been used in similar CAR constructs. An example is disclosed in June. The CAR disclosed in June is similar that of the instant claims as it comprises a CD19 antigen binding domain, a transmembrane domain, and a CD3 zeta signaling domain (claim 90). The a CD19 antigen binding domain comprises a scFv comprising the amino acid sequence of SEQ ID NO: 20 (claim 96), which is 100% identical to SEQ ID NO: 12 recited in instant claim 4. In view of June, it would be obvious for one of skill in the art to substitute a sequence having SS at the carboxyl terminus for the trivially different sequence disclosed in Rosenthal when building a CAR.
Rosenthal teaches encoding nucleic acids, lentiviral vectors, retroviral vectors comprising a promoter, and host cells expressing the CAR [0210-0218], as in pending claims 13, 14, 16, and 19. Rosenthal teaches methods of treating cancer, including non-Hodgkin's lymphoma and chronic lymphocytic leukemia [0009], as in pending claims 25 and 30. In Rosenthal, the host cells are myeloid cells, not T cells as in claims 20, 21, 23, 26, and 27. However, June teaches that the CD19-specific CAR is to be use to modify T cells for therapeutic administration (Abstract, claim 90).
The products of the instant claims are collections of known components, each performing the function for which they are known in the prior art. Therefore, the products and methods of claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 20, 21, 23, 25-27, 30, and 32 are prima facie obvious in view of Rosenthal and June.
Claims 5, 6, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180186878 (Rosenthal) and US 20150050729 (June), as applied to claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 20, 21, 23, 25-27, 30, and 32 above, and further in view of US 20190135937 (Zhang; of record) and US 20200399393 (Ji; of record).
As noted above, Rosenthal teaches a CAR having the same CD19 antigen binding and intracellular signaling domains as in the instant claims. The CAR amino acid sequences of pending claims 10 (SEQ ID NO:24 and 12 (SEQ ID NO:14) are, respectively 93.0% and 91.2% identical to SEQ ID NO:21 of Rosenthal. Thus, Rosenthal does not teach the 95% identity limitations of claims 10 and 12. The differences lie in the respective signal peptide and hinge regions. SEQ ID NO:14 further differs by the presence of a myc tag, having the sequence DIEQKLISEEDL.
The signal peptide in SEQ ID NO:24 and SEQ ID NO:14 is SEQ ID NO:9. The instant disclosure teaches SEQ ID NO:9 as exemplary, and acknowledges that other species of signal peptide are useable. This is reflected in the recitation of a generic signal peptide in pending claim 8. Furthermore, the SEQ ID NO:9 signal peptide is known for use in the art of making chimeric antigen receptors. For example, see Zhang, Table 1, SEQ ID NO: 19, which is 100% identical to SEQ ID NO:9. Therefore, the signal peptide differences between the presently claimed CAR and SEQ ID NO:21 of Rosenthal indicate obvious design alternatives known to persons of skill in the art.
Both the present application and Rosenthal generically describe the hinge region as “CD8 hinge”. The hinge region in Rosenthal includes stretches of sequence identity to amino acids 4-46 of SEC ID NO: 4 and amino acids 2-40 of SEQ ID NO:5, both of which are also present in SEQ ID NO: 13. Similarly, June teaches a CD8a hinge [0056]. The present disclosure does not assert any functional difference attributable to the hinge sequence differences that do exist relative to the prior art. Furthermore, the use of structurally similar CD8 hinges in the making of chimeric antigen-binding constructs is known in the art. For example, Ji discloses a hinge sequence (SEQ ID NO: 19) that is 100% identical to SEQ ID NO: 13. Therefore, the hinge differences between the presently claimed CAR and SEQ ID NO:21 of Rosenthal indicate obvious design alternatives known to persons of skill in the art.
The inclusion of a myc tag to facilitate identification and purification of recombinant proteins is well known the art. Relevant examples are found in Ji [0134][0344] and Zhang [0139][0142]. It would be obvious for one of skill in the art to modify the anti-CD19 CAR of Rosenthal to include a my tag. Therefore, the presence of a myc tag in SEQ ID NO:14 is not an inventive distinguishing feature relative to SEQ ID NO:21 of Rosenthal.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W. Please note the examiner’s part-time schedule. 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, Joanne Hama can be reached on 5712722911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DANIEL C GAMETT/Primary Examiner
Art Unit 1647
Prosecution Insights