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 05/20/2024 have been entered in full. Claims 27-46 are pending and under consideration.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
The claims filed on 05/20/2024 comprise two claims numbered as 44 and no claim 45. For purposes of further examination, the second claim 44 will be referred to as claim 45. Applicant should include a corrected claim listing in response to this Office action.
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).
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Claims 27-29, 31-39, and 42-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-6, 15, 25, and 27 of U.S. Patent No. 11918605. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Patented claim 1 is drawn to a pharmaceutical composition comprising genetically modified monocytes of pending comprising a polynucleotide encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain of a stimulatory and/or co-stimulatory molecule, as is pending claim 27. In patented claim 1, the antigen binding domain binds HER2/neu, which is a tumor antigen as in pending dependent claims 31-33, and the intracellular domain comprises an intracellular domain of CD3-zeta, as in pending dependent claim 38. The CAR of patented claim 1 further comprises a CD8 hinge domain, as in pending claims 36 and 37. The cells in patented claim 1 are CD14+/CD16+, whereas the cells in pending depending claim 43 are CD14+. Therefore, patented claim 1 is drawn to a species that would anticipate the generic pharmaceutical composition comprising genetically modified monocytes of pending claims 27, 31-33, 38-38, and 43.
As the pending and patented independent claims are related as genus and species, the respective dependent claims are likewise related as they recite identical or overlapping limitations. Patented claim 27 and pending claims 28 and 29 each recite differentiation into macrophages, specifically M1 macrophages. Patented claim 15 recites that the antigen-binding fragment of the CAR is a scFv, as in pending claims 34 and 35. Pending claims 4-6 recite a viral vector, as in pending claim 44.
Claims 45 and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, and 20 of U.S. Patent No. 11527589. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Patented dependent claim 20 and pending claim 46 are each drawn to a method of treating a solid tumor comprising administering a population of genetically modified human monocytes comprising a chimeric antigen receptor (CAR) or a polynucleotide encoding the CAR, wherein the CAR comprising a HER-2/neu binding domain, a transmembrane domain, and an intracellular domain comprising a CD3-zeta intracellular domain, wherein the CAR is capable of inducing monocytic differentiation of the modified human monocytes into macrophages or dendritic cells (DCs). Pending claim 45 is generic to both pending claim 46 and patented claim 20 as claim 45 does not recite the specificity of the antigen-binding domain or the intracellular signaling domain of the CAR.
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 27-46 are rejected under 35 U.S.C. 103 as being unpatentable over US 20160145348 (Stephan, of record), Yong et al., Open Gene Ther. J., 5:1-11, 2013 (Yong 2013; of record), Yong CS, et al. Oncotarget. 2016 Jun 7;7(23):34582-25498 (Yong 2016, of record), Koya et al., J Immunother. 2003 Sep-Oct;26(5):451-460 (Koya) and Wang et al, Front Immunol. 2014 Nov 28;5:614 (Wang) .
Stephan teaches modifying cells to express chimeric antigen receptors which comprise a binding domain and an effector domain and a transmembrane domain [0099-0102]. The method of modification encompasses transfecting macrophages or monocytes with a polynucleotide encoding a molecule that binds a tumor antigen [0202-0210]. In particular embodiments, modified monocytes/macrophages target and destroy cancer cells [0067]. Examples of intracellular signaling domains include the cytoplasmic sequences of the CD3 zeta chain, and/or co-receptors that act in concert to initiate signal transduction following CAR engagement [0105]. Tumor antigens include BAGE, β-catenin, CEA, GAGE, gp100, G250, HER-2/neu, MAGE, MART, MUC, survivin, or WT1 [0182], which are recited in pending claim 32. Stephan teaches that the binding domain is CAR can be an scFv antibody [0088], as in pending claims 34-35. Stephan teaches that the binding domain is CAR can comprise a hinge domain as in pending claim 36 [0108].
Therefore, Stephan teaches or suggests modified monocytes/macrophages that are structurally identical to those of the instant claims.
Yong 2013 teaches macrophages transfected via electroporation with a nucleic acid encoding a CAR, said CAR comprising a scFv specific for ErB2 (HER2/neu) and signaling domains from CD28 and CD3-zeta. (See the abstract and page 2, first and second columns.) The macrophages exhibited effector function (IFN-g secretion) in an antigen-specific manner (p. 8, Fig. 6).
In subsequent work, Yong 2016 used the same CAR in a novel mouse model utilizing a pan-hematopoietic promoter to drive the expression of a CAR directed against the tumor antigen ErbB2 within most immune subsets. Macrophages from the transgenic mice exhibited TNF-a and IL-6 secretion in an antigen-specific manner (Fig. 4) and it was evident that the macrophage subset contributed to the anti-tumor effect of adoptively transferred transgenic cells (Fig.7).
The results of Yong 2013 and Yong 2016 are consistent with M1 activation of macrophages. Yong 2013 and Yong 2016 reinforce Stephan by providing further motivation and expectation of success to make and use monocytic cells expressing CAR comprising a binding domain specific for a tumor antigen a CD3-zeta intracellular signaling domain.
Stephan, Yong 2013 and Yong 2016 do not teach embodiments comprising intracellular domains in addition to, or alternative to, CD28 and CD3-zeta, as in claims 39-41. Toll-like receptor signaling is a known stimulus M1 polarization of macrophages (Wang). Lentiviral delivery of CD40L enhances maturation of monocyte-derived dendritic cells (Koya). Therefore, one of skill in the art would reasonably expect that a CAR comprising the intracellular domain of a TLR or CD40L in place of or in addition to the CD28 and CD3-zeta of Stephan, Yong 2013 and Yong 2016 would produce a desirable phenotype in monocytic cells.
In summary, the elements of the pending claims are known or suggested in disclosures made before the filing of the instant application. “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398 at, 82 USPQ2d at 1395. It is noted that the instant application relies on the predictability suggested by the cited references, as all teaching is prophetic, and no new results are disclosed.
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.
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/DANIEL C GAMETT/Primary Examiner
Art Unit 1647