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 .
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 49-60, 62-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davila et al (US 20130287752 A1, e.f.d. 12/14/2010, of record) in view of Lu et al (Mol. Cancer Ther., 2006, of record) and Leamon et al (US 20110172254 A1, of record).
Davila et al teach a two-component system for lysis of target (tumor) cells comprising a tagged protein and CAR T cells specific for the tagged protein (the tagged protein is exemplified by FITC-tagged antibodies specific for tumor cells). The “protein” portion of the tagged protein may be any molecule that binds to a target cell (¶ [0052]). Davila et al teach T lymphocytes expressing CAR molecules wherein the CAR molecules comprise: a -FITC scFv; a CD8 transmembrane domain; a CD28 or a 41BB co-stimulation domain; and a CD3 signaling domain. See Fig. 1A, the abstract, ¶[0003]. The tagged protein may comprise a linker (¶[0039]). Types of tumors to be targeted are colon or pancreatic (¶ [0007]). Transfection of T cells can be achieved with retroviral vectors (¶[0044]-[0045]). Cytotoxic T cells and target cell lysis are taught in ¶’s [0031], [0079], [0084], Figs 1 and 2. The figure graphs indicate lysis up to and including the % in claims 62. Davila et al do not teach their methods to induce a cytokine storm, nor to be endocytosed by the targeted cells. According to MPEP § 2112.01, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Davila et al do not specifically teach a tumor ligand that is folate as a component of the conjugate molecule, nor a specific linker.
Lu et al teach a bispecific ligand comprising folate linked to FITC by an ethylenediamine linker (abstract and Fig. 1 A). The purpose of such a ligand is to target M109 lung cancer tumor cells expressing folate receptor (abstract and Introduction). Lu et al do not indicate that the FITC-folate conjugates are endocytosed by the cells or create a cytokine storm. According to MPEP § 2112.01, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Leamon et al describe the folate-FITC molecule used by Lu et al (Table 2, page 36, termed "EC17"), and teach that such molecules can comprise a linker other than ethylenediamine. Such linkers include hydrophilic amino acids (¶'s [0066]-[0067]).
The claimed methods and therapeutic are essentially disclosed by Davila et al with the exception of the specific tumor ligand and linker limitations. The ordinary skilled artisan, seeking to treat tumor cells, would have been motivated to use a folate-FITC conjugate of Lu et al with the methods and therapeutics of Davila et al because Davila et al teaches any such molecule specific for tumor cells can be used, and the system of Davila et al is already designed to be specific for the label used by Lu et al (FITC). It would have been obvious for the skilled artisan to do this because of the known benefit of generating therapeutics specific for tumor cells as taught by Lu and Davila et al. Further, it would have been obvious to one of ordinary skill in the art to have substituted the folate-FITC of Lu et al for the antibody-FITC taught by Davila et al. The substitution of one known element (folate-FITC with specific binding to cancer cells) for another (FITC-antibody, also with specific binding to cancer cells.) would have been obvious to one of ordinary skill in the art at the time of the invention since the substitution of the folate-FITC would have yielded predictable results, namely, a molecule that binds cancer cells but also comprises a FITC domain capable of being recognized by the FITC-specific CAR cells of Davila et al.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in chemistry, cloning, immunology and CAR therapy. Therefore, the level of ordinary skill in this art is high.
Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Claim 49-67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davila et al (US 20130287752 A1, e.f.d. 12/14/2010, of record) in view of Lu et al (Mol. Cancer Ther., 2006, of record), Leamon et al (US 20110172254 A1, of record) and June et al (US 8,906,682, of record).
The teachings of Davila, Leamon and Lu et al are as above and applied as before. These references do not teach lentiviral vectors.
June et al teaches the production of CAR T cells with lentiviral transfection. See, e.g. Fig. 1.
The claimed therapeutic is essentially disclosed by Davila et al with the exception of the lentiviral limitations. The ordinary skilled artisan, seeking to treat tumor cells, would have been motivated to use a lentiviral vector with the methods and therapeutics of Davila et al because June et al teaches such vectors can be used to create the desired CAR T cells. It would have been obvious for the skilled artisan to do this because of the known benefit of generating therapeutics specific for tumor cells as taught by Davila, Lu and June et al. All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in chemistry, cloning, immunology and CAR therapy. Therefore, the level of ordinary skill in this art is high.
Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 49-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-12, 16-19, 21-24 and 31 of U.S. Patent No. 12,150,981. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant generic methods and therapeutic are taught by the specific methods and therapeutic, directed to FITC-folate conjugates, of the ‘981 patent.
Conclusion
No claim is allowed.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638
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