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 .
Claims 22-33 are pending as amended 6/21/24 and are considered herein.
Formalities
The drawings of 2/28/24 are accepted.
The specification as amended 6/21/24 is accepted.
The IDS filings and references therein of 5/8/26; 9/30/25; and 6/21/24, have been considered and a signed copy of each is provided herewith.
Applicant’s priority is noted to be as follows:
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Double Patenting
It is noted that the parent Application to the present Application evolved into US PAT NO 11,959,084, and is drawn to nucleic acid constructs in a more generic fashion, with two ORFs separated by the TRM and cleavage site, and even contains limitations to CARs as being one of the ORFs. However, there is no claim to IL-12 and given the number of possible molecules which could be used, even just for cytokines, and the lack of predictability that they would achieve physiological levels of use, in this context, the Artisan would not have chosen IL-12. Therefore, no NSDP rejections were made thereto.
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 32 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 32 is drawn to increasing T cell survival in a tumor microenvironment, however, all that is done is to administer a cell with a CAR recognizing a tumor-specific antigen on the tumor. Thus, it is not clear how this increases T cell survival, as no T cells are required to be present.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 31-33 are to generically blocking immune-suppressive signalling in a tumor microenvironment in a subject, increasing T cell survival in a tumor microenvironment in a subject, and treating a solid tumor in a subject, where a cell is administered, the cell expressing the construct of Claim 22.
The separate claiming of blocking signaling, increasing T cell survival, and treating a solid tumor, indicates that they can each be performed separately, through some sort of difference in the methods. However, as the examiner will show below, all rely on the presence of IL-12 to increase T cell survival, block immune-suppression by the tumor, and treat the solid tumor.
The specification teaches that IL-12 is a cytokine that enhances the cytotoxic activity of NK and cytotoxic T cells (p. 19, penultimate paragraph), stimulates growth and function of T cells (e.g., Id., paragraph 6), and stimulates production of IL4, thereby stopping suppression of IFN-gamma (e.g., Id.). Thus the CAR-T cells are made to express molecules that block immune-suppression in a tumor and enable survival in hostile tumor microenvironment (e.g., p. 3, paragraph 2). Therefore, from this, we can see that all three occur together, i.e., the CAR-T cells attack the tumor, and survival is increased through IL-12 suppression of the tumor response and increasing the CAR-T cell survival, thereby potentiating the attack on the solid tumor. This is further backed by the teachings in Applicant’s Example 8, recognizing all of what has been said above, then demonstrating potentiated survival of the immune cells in mice.
The Art teaches all of these things through the presence of IL-12. To wit, Yeku, et al. (2016) “Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumor efficacy”, Biochemical Society Transactions, 44(2): 412-18, teaches all of these same aspects (e.g., pp. 413-414).
Thus, the Artisan would not have understood Applicant to have been in possession of each of these claims separately, as the components all act in concert, i.e., you are doing all three when you add the cell expressing the CAR and the IL-12.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 31-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are generic for the cell that expresses the CAR and IL-12/Flexi-IL-12 through the TRM. In Claim 31, it blocks immune suppressive signalling in a tumor microenvironement, increases T cells survival in the tumor microenvironment in Claim 32, and treats a solid tumor in Claim 33.
The specification teaches that the expression of IL-12 stinulates IFNgamma and TNFalpha from T and NK cells, and reduces IL-4 suppression by IFNgamma. Further, It enhances these cells (e.g., 20). Fruther, it is taught that IL-12 is positive for the NK cell and CAR-t cells (pp. 19-20, paragraph bridging). Moreover, the CAR is taught in the context of tumors, as being expressed in the cytotoxic T cells (e.g., Example 8).
Thus, from the specification, the cell types appear to be limited to cytotoxic T cells. However, the mention of NK cells and the positive effects of IFNgamma, is further backed by the prior art, for CAR-NK cells and therapy of cancers (e.g., Hu, et al. (2018) “Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy”, Acta Pharmacologica Sinica, 39: 167-76, ABSTRACT). Hence, while it is not ready for therapy in humans, it is certainly disclosed for use in animal models of cancer.
Therefore, given the disclosure, and limited forms of cells that respond to the IL-12 in a positive manner, and limited number of cell types known to be able to treat cancers with CARs, coupled with the hundreds of cell types in the body, the Artisan would not have understood Applicant to have been in possession of more than CAR-T cells or CAR-NK cells in the methods claimed.
Art Made of Record
The first disclosure of a vector utilizing TRMs to co-express, at diminished level, IL-12, with a CAR is that of Applicant’s own disclosure: Sillibourne, et al. (August 2022) “A compact and simple method of achieving differential transgene expression by exploiting translational readthrough”, Biotechniques, 72(4): 10.2144/btn-2021-0079, 10 pages long. It is noted that it is not only Applicant’s disclosure, but is published after the priority accorded Applicant.
Conclusion
Claims 22-30 are allowable.
Claims 31-33 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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