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 63-77 are pending as amended 7/10/23, and are considered herein.
Formalities:
The drawings of 4/21/23 are accepted.
The specification of 4/21/23 is accepted.
The sequence listing has been found to be proper format by the office.
The IDS filings of 9/8/25; 8/28/24; and 6/15/23 have been considered and signed-off upon herewith.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 63-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,673,964. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 63: Patent Claim 1 teaches a pharmaceutical composition comprising two populations of T cells, each having an mutated endogenous CD5 gene, and one population (defined as the first population) also comprising a chimeric antigen receptor. The distinction between the present and patent claims, is the patent only specifically claims that the CAR is in the T cell, but does not claim how it gets there. On the other hand, the sole, and thus essential written description for how this CAR gets into the cell of the first population is through transfection with a nucleic acid that expresses this chimeric antigen receptor (e.g. patent and the present specification, section “Introduction of Nucleic Acids”). Also, the specification of both the present Application, and the Patent, in the definitions section, recites:
The term “chimeric antigen receptor” or “CAR,” as used herein, refers to an artificial T cell receptor that is engineered to be expressed on an immune effector cell and specifically bind an antigen. CAR5 may be used as a therapy with adoptive cell transfer. T cells are removed from a patient and modified so that they express the receptors specific to a particular form of antigen. In some embodiments, the CAR5 has specificity to a selected target, for example a B cell surface receptor. CAR5 may also comprise an intracellular activation domain, a transmembrane domain and an extracellular domain comprising a tumor associated antigen binding region. In some aspects, CAR5 comprise an extracellular domain comprising an anti-B cell binding domain fused to CD3-zeta transmembrane and intracellular domain.
There is absolutely no description for how to insert a CAR protein into the cell to make the pharmaceutical composition.
Claims 64-65: The patent is to T cells, and all T cells are lymphocytes. The claims of the patent are to populations of T cells (e.g., Claim 1), methods of using them (e.g., Claims 11 and 15), and CARs that utilized in the T cells (e.g., Claim 18).
Claim 66-68: E.g., Patent Claim 2 recites that the mutated CD5 is a gene-edited endogenous CD5.
Claim 69-71: E.g., Patent Claim 9 teaches the mutant CD5 gene may be CRISPR mutated CD5 gene.
Claim 72-74: e.g., Patent Claim 3 requires a decreased expression of CD5 in the two populations.
Claim 75-77: Claims 4 and 17 teach, in the alternative, antigen binding domains to several markers, one of which is CD5, indicating that many embodiments include an antigen binding domain that does not bind CD5. Additional, Claims 5 and 14, depending back to Claim 1, teaches that the antigen binding domain binds to CD5, indicating the broad claims specifically embrace antigen binding domains that do not bind to CD5. Additionally, Claim 15 teaches it does not bind CD5.
Thus, in light of the patent, the invention is obvious. The Artisan would make it, and expect success, as it is claimed subject matter, and/or provided as essential written description for such claimed subject matter in the patent.
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 63-77 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 drawn to a pharmaceutical composition comprising two populations of generic immune cells, each population having a mutated endogenous gene for CD5, and one population (defined as first) also comprising a generic nucleic acid encoding a generic exogenous protein.
In the context of the description, Applicant’s description teaches T cell lymphomas/leukemias have poor prognoses with few available treatments CAR T cell therapy has demonstrated efficacy for B cell neoplasms, but extending the same to T cell malignancies has been a problem, because most target antigens are shared between normal and malignant cells, leading to CAR T cell fratricide, as it binds to normal cells exhibiting the marker. Applicant proposes to rectify this problem of targeting T cell cancers with CAR T cells, and T cell fratricide. (Background of the Invention)
Throughout the specification, it is described to use CAR T cells, targeting CD2, CD5, or CD7, with concurrent administration of modified cells wherein the equivalent CD2, CD5, or CD7 has been knocked-out (e.g., Summary of the Invention). The specifications examples demonstrate the treatment of T cell malignancies, including in animal models, with the compositions so-made, i.e., the use of CAR T cells, with or without CD5 knocked out, and a second subset of T cells, with only CD5 knocked out (i.e., no CAR receptor). The CRISPR system was made with sgRNAs for one of CD2, CD5, or CD5, and utilized to knock out expression of these gene in jurkat cells (jurkat cells are a cell line of immortal human T cells, used in, e.g., the study of leukemia). Pages 69-70. Example 1 teaches that it is known to target CD19 in B cell lymphoma B-NHL, and here a parallel strategy is used to edit normal T cells to be CART resistant (e.g., Figure 2). It is stated that CART therapy becomes feasible when expression of CD2, CD5, or CD7 is temporarily stopped, thus avoiding CART-mediated killing and immunodeficiency that subsequently follows upon killing normal cells. Example 2. Teaches Anti-CD5 CART cells (CART5) and CD5 KO normal T cells can be used in a two-prong immunotherapy (e.g., Figure 3). Example 2 teaches anti-CD2 (CART2) and CD2 KO normal T cells, in parallel examples, following Figure 3. Example 4 teaches CART2 and CART5 testing, where they recognized and killed T cells expressing the appropriate marker, but did not kill themselves. Example 7 teaches similar with CART to CD7 (CART7) and normal CD7 KO T cells. Example 6 teaches dual specific CARS joined by a p2a sequence (i.e., CAR5 and CAR2). Example 6 teaches CD5 KO enhances CART immunotherapy, demonstrating the KO CD5 CART5 cells more effective than CART5 cells that express CD5.
Through all of this, there is no discussion of the CD5 markers, and their prevalence in other immune cells and which immune cell cancers to treat, and if the same will produce increased immune response to neoplasms. There is not even a discussion of which immune cells are part of the invention with expressing a CAR for CD5, and its silenced expression, aside from T cells. To wit, the Artisan is left to determine which cells behave similar to the present T cells and CD5 situation. Even the discussion of CD19 and B cells, another form of immune cell, recognizes that only a rare subset of B cells even express CD5 (Example 2), and what is important for the B cells is CD19, not CD5 (e.g., p. 79). Further there is no description of other than CARs being expressed on the T cells, to recognize CD5, in the specification. It should be noted however, TCRs are disclosed generally and linked to any cell that comprises a TCR, including several types of T cell (p. 21).
The Art, however, recognizes many forms of immune cell. It is assumed Applicant is well aware that the immune system goes far beyond B and T cells, including graulocytes, which may be basophils, eosinophils, and neutrophils, Mast cells, monocytes, dendritic cells, natural killer cells, adaptive cells including B and T cells, each having several subtypes, as well as other cells of the body. The Art does not teach which of these are treated due to expression of CD5, and would benefit from such CART therapy, much less how the T cells will replace the loss of these cells, for the T cells that are knocked out for CD5. See “Immune Cells: Types of Immune Cells”, https://www.niaid.nih.gov/research/immune-cells, author unknown, published by NIAID, Washington, DC, 2014, no volume or journal, 7 pages long. Moreover, some immune cells, including some T cells turn off the immune system, and thus, would be expected to stop immune response to cancer, thereby negating the effect thereon if they expressed a protein to recognize CD5, and the Artisan is left to wonder which proteins would reverse this effect. For example, T regulatory cells are well known to be therapeutic against autoimmune disease, not potentiate an autoimmune function needed (e.g., Goswami, et al. (2022) “Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders – Advances and challenges”, Human Vaccines & Immunotherapeutics, 18(1): e20351117, 16 pages long, e.g., ABSTRACT). Further, with regard to the Art, it is also well known that there exist many many proteins, millions, and they may not even be displayed on the immune cell to target a CD5, or to have some undefined function to make another immune cells work against a cancerous cell. Moreover, the structure required is not even known, for the targeting of these proteins. Lastly, it should be noted that the Art recognizes that CAR-T cells are generally known to be cytotoxic T cells (e.g., Davila, et al. (2016) “CD19-Targeted CAR T Cells as Novel Cancer Immunotherapy for Relapsed and Refactory B-Cell Acute Lymphoblastic Leukemia”, Clinical Advances in Hematological Oncology, 14(10): 802-808, provided as an HHS Public Access Author Manuscript, 11 pages long, from https://pmc.ncbi.nlm.nih.gov/articles/PMC5536094/pdf/nihms886576.pdf). See pages 4-5.
Thus, given the wide range of cell types, wide range of proteins, in the cells, as well as on the surface, along with the sole contemplation of CD5 with the CART therapy of T cells, which are the main expressers of CD5, the Artisan would not have understood Applicant to have been in possession of the breadth of cell types generically claimed as immune cell, nor the generic exogenous nucleic acid encoding a generic protein. (I.e., Applicant only possesses cytotoxic T cells, and an anti-CD5 CAR as the exogenous protein.)
Conclusion
No claim is allowed.
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