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 preliminary amendments of 12/15/2023 have been entered in full. Claims 1,2,5-8,10,12-14, 16, 19-21, 23, 25-27, and 30 are pending.
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.
Claim 8 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 8 is dependent from claim 1 and it recites “wherein the CAR comprises a myc tag (SEQ ID NO: 15)”. The recitation of SEQ ID NO: 15 is confusing. The sequence listing identifies SEQ ID NO: 15 as a nucleic acid sequence which encodes an entire CAR, CAR2-63, not a myc tag. It appears that the correct sequence for the myc tag should be SEQ ID NO:10.
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.
Claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 25, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20180186878 (Rosenthal).
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. 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 91.1% identity to SEQ ID NO:2, thereby conforming to the sequence limitations of pending claims 1, 2, and 7. The anti-CD19scFV component is CD19 is 99.5% identical to SEQ ID NO:12, which is encompassed by pending claim 4. 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.
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 5, 6, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180186878 (Rosenthal) as applied to claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 25, and 30 above, and further in view of US 20190135937 (Zhang) and US 20200399393 (Ji).
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. 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.
Claims 20, 21, 23, 26, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180186878 (Rosenthal) as applied to claims 1, 2, 4, 7, 8, 13, 14, 16, 19, 25, and 30 above, and further in view of US 20190135937 (Zhang) and US 20210060073 (Trager).
As noted above, Rosenthal teaches retroviral vectors comprising a promoter, and host cells expressing the CAR, and methods of treating cancer by administering cells expressing the CAR, as in pending claims 19, 25 and 30. In Rosenthal, the host cells are myeloid cells, not T cells as in claims 20, 21, 23, 26, and 27.
Like both Rosenthal and the instant application, Zhang discloses a CD19-based chimeric antigen receptor [0007]. Zhang summarizes the state of the art which identifies CD19 as a target for the effective and safe treatment of hematological malignancies in B lymphocytes [0003-0004]. All of the prior work employed CAR-T cells, i.e. T cells engineered to express a chimeric antigen receptor specific for CD19. Zhang likewise teaches anti-CD19 CAR-T cells. The Zhang construct comprises an CD28 intracellular signal transduction domain, SEQ ID NO:8 [0024], which is identical to SEQ ID NO:7, recited in pending claim 1. Zhang teaches that the CD28 intracellular signal transduction domain and the CD3-ζ domain function in T cells [0003][0024].
Like both Rosenthal and the instant application, Trager discloses a CAR comprising an anti-CD19 moiety, a CD8a hinge domain, a CD28 signaling domain, and a CD3-ζ domain (among other domains; [0184]. Trager teaches T cells expressing the CAR [0267-0268] as well as methods of treating cancer, specifically leukemia, by administering the CAR-T cells [0256][0265][0272].
In view of Zhang and Trager, it would be obvious to use an anti-CD19 CAR similar to that of Rosenthal to make CAR-T cells for the treatment of cancers, especially leukemias. Therefore, the choice to engineer T cells instead of myeloid cells in not an inventive distinction between the instant claims and Rosenthal.
Conclusion
No claim is allowed.
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 9:00 am-5:30pm, EST. 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.
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/DANIEL C GAMETT/Primary Examiner
Art Unit 1647