DETAILED ACTION
The amendments to the claims in the response filed 8/21/2023 are acknowledged and entered into the record.
Claims 1-8, 11-13 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 5-8 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.
Claims 5-8 recite “preferably” rendering the claim indefinite because the claim includes elements not actually disclosed, thereby rendering the scope of the claim unascertainable.
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.
Claim(s) 1-8, 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Tamada et al. (US Patent 10,316,102) in view of Craddock et al. (J Immunother. 2010 October; 33(8): 780-788, cited on IDS filed 8/21/2023) as evidenced by the instant specification.
The claims are drawn to a fusion protein comprising a chimeric antigen receptor, wherein the fusion protein comprises a chimeric antigen receptor comprising a scFv targeting GD2, a 2A peptide, IL-7, a 2A peptide and CCR2b which are sequentially linked in series. The claims are further drawn to a T-cell expressing said fusion protein and a method of treatment comprising administering said T-cell or composition comprising said T-cell. It is noted the SEQ ID NOs recited in the claims are “preferably” and therefore not a required limitation.
Tamada et al. teach a chimeric antigen receptor (CAR) expression vector, comprising a CAR, a 2A peptide, IL-7, a 2A peptide, and CCL19 sequentially connected in series (see figure 2), wherein IL-7 and CCL19 are immunological function-promoting factors, and can improve the migration capability of CAR-T to tumor cells and methods of treatment comprising administering said CAR-T-cells. Tamada et al. teach IL-7 comprising SEQ ID NO: 3, which has 100% identity to instantly claimed SEQ ID NO: 2. Tamada et al. disclose “chimeric protein in which a single chain antibody that recognizes a cell surface antigen on a cancer cell is fused with a signal transduction region that induces the activation of a T cell.” Tamada et al. teach wherein the cell surface antigen for example is GD2. Tamada et al. further disclose the CAR consisting of a transmembrane domain, a 4-1BB costimulatory intracellular signal region and a CD3ζ intracellular signal region. Tamada et al. further disclose a human CD8 hinge region. Tamada et al. does not teach the chemokine receptor CCR2b. This deficiency is made up for by Craddock et al.
Craddock et al. teach tumor trafficking of activated T cells (ATCs) bearing a chimeric antigen receptor specific to the tumor antigen GD2 can be enhanced by means of the co-expression of CCR2b. Craddock et al. teach CCR2b can improve the migration capability of CAR-T cells to tumor sites because GD2-CAR transduced activated t-cells lacked expression of CCR2b, which directs migration toward CCL2, a chemokine produced by many tumors. Craddock et al. teach single-chain variable fragment (scFv), derived from GD2-recognizing antibody 14g2a, which is the same GD2 targeting antibody recited in the instant specification having instant SEQ ID NO:1.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make and use a T-cell expressing a chimeric antigen receptor comprising a scFv targeting GD2, a 2A peptide, IL-7, a 2A peptide and CCR2b in sequence based on the teachings of Tamada et al. and Craddock et al. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Tamada et al. that cytokines, chemokines, and signal regulatory proteins which are factors enhancing the immune functions of T cells, and constructed a vector for the co-expression of CAR and the factors enhancing the immune functions of T-cells, to replace the CCL19 with the chemokine CCR2b as taught by Craddock et al. to promote the trafficking of CAR-T cells to tumors because GD2-CAR transduced activated t-cells lacked expression of CCR2b, which directs migration toward CCL2, a chemokine produced by many tumors.
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 1-8 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Tamada et al. and Craddock et al. as applied to claims 1, 2, 4-8, 11-13 above, and further in view of Liu and Jin (CN108728460, published 11/2/2018, cited on IDS filed 8/21/2023).
The claims are drawn to a fusion protein comprising a chimeric antigen receptor, wherein the fusion protein comprises a chimeric antigen receptor comprising a scFv targeting GD2 (having SEQ ID NO:1), a 2A peptide (having SEQ ID NO: 4), IL-7 (having SEQ ID NO: 2), a 2A peptide (having SEQ ID NO: 4) and CCR2b (having SEQ ID NO: 3) which are sequentially linked in series and CD8α hinge region (having SEQ ID NO:5). The claims are further drawn to a T-cell expressing said fusion protein and a method of treatment comprising administering said T-cell or composition comprising said T-cell.
The teachings of Tamada et al. and Craddock et al. are presented above. Tamada et al. and Craddock et al. do not teach all of the preferred SEQ ID NOs. This deficiency is made up for by Liu and Jin.
Liu and Jin disclose the amino acid sequences of the GD2 single-chain antibody, the CD8α hinge region, the CD8 transmembrane region, the 4-1BB intracellular region and the CD3ζ intracellular region. Liu and Jin teach 100% identity to instantly claimed SEQ ID NOs: 5, 6, 7, and 8 (see alignment attached).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make and use a T-cell expressing a chimeric antigen receptor comprising a scFv targeting GD2, a 2A peptide, IL-7, a 2A peptide and CCR2b sequentially, having the instantly claimed sequences, which are all well known components known in the CAR-T prior art. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on conventional experiments to substitute suitable amino acid sequences of CCR2b, other types of transmembrane regions and intracellular signal regions to arrive at the instantly claimed CAR-T fusion protein based on the teachings of Tamada et al., Craddock et al., and Liu and Jin for a more effective CAR-T therapeutic.
Conclusion
Claims 1-8 and 11-13 are rejected.
No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEERA NATARAJAN whose telephone number is (571)270-3058. The examiner can normally be reached M-F 9AM - 5PM.
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, JULIE WU can be reached at 571-272-5205. 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.
/Meera Natarajan/Primary Examiner, Art Unit 1643