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 .
DETAILED ACTION
Claims 1-19 are pending.
2.Applicant's election without traverse of species of the TCR polypeptide having combination of all SEQ ID N: 87-92 in the reply filed on 01/06/26 is acknowledged.
Claims 1-19 read on method of treating or preventing cancer in a mammal, comprising administering a host cell expression TCR having antigenic specificity for mutated p53 are under consideration in the instant application.
3. 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.
4. 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.
5. Claims 1-19 are indefinite for being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 706.03(Y).
6. The following is a quotation of the first paragraph of 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.
7. Claims 1-19 are rejected under 35 U.S.C. 112, first paragraph, because the specification, does not reasonably provide enablement for a method of treating any cancer in mammal, comprising administering to the mammal a population of any host cells wherein said host cells comprises a recombinant expression vector comprising a nucleotide sequence encoding a TCR having antigenic specificity for mutant human p53 of SEQ ID :1 and wherein TCRs comprises the amino acid sequences of all of SEQ ID NO: 87-92.The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and or use the invention commensurate in scope with this claim.
The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification only discloses very specific examples of isolating reactive T cells from very specific individual patient with very specific type of cancer and isolating anti-mutant p53 TCRs from very specific individual patient. Examples 11 and Table 43 only disclosed very specific treatment of individual patient with very specific p53 mutation-related TIL. However even the data in the table 43 are not conclusive since out of 10 patient 6 patient shows no response ( see page 120 of the instant Specification).
The specification does not adequately teach how to effectively treat treating any cancer in mammal, comprising administering to the mammal a population of any host cells wherein said host cells comprises a recombinant expression vector comprising a nucleotide sequence encoding a TCR having antigenic specificity for mutant human p53 of SEQ ID :1 and wherein TCRs comprises the amino acid sequences of all of SEQ ID NO: 87-92.
The specification does not teach how to extrapolate data obtained from in vitro studies and limited in vivo data to the development of effective in vivo mammalian including human therapeutic treatment, commensurate in scope with the claimed invention. Therefore, it is not clear that the skilled artisan could predict the efficacy of a method of treating of treating any cancer in mammal, comprising administering to the mammal a population of any host cells wherein said host cells comprises a recombinant expression vector comprising a nucleotide sequence encoding a TCR having antigenic specificity for mutant human p53 of SEQ ID :1 and wherein TCRs comprises the amino acid sequences of all of SEQ ID NO: 87-92. Moreover, as has been stated previously the data shown in Table 43 indicated that out of 10 patient 6 shows were none responsive . As such, the invention must be considered unpredictable. Thus in the absence of working examples or detailed guidance in the specification, the intended uses of any pharmaceutical composition comprising an antisense nucleic acid are fraught with uncertainties.
Plautz et al., ( Archivum Immunologiae et Therapiae Experimentalis, 2003, 51, 245–257) teach that the goal of effective, sustained T cell immunotherapy for cancer patients remains unrealized despite encouraging anecdotal instances of dramatic regression of metastatic disease without toxicity. Unfortunately, the results of numerous clinical trials employing single peptide epitopes indicate that more effective strategies to induce a broadened immune response through intermolecular epitope spreading may be required to generate clinically relevant immune effects These strategies are still in very early stages of clinical development and it will be several years before their efficacy and definition of the relevant parameters for improvement are defined. Adoptive transfer of ex vivo generated tumor-reactive T cells currently remains the most potent method to cure bulky metastatic disease in preclinical models. T
The state of the prior art and the level of one of ordinary skill relate to predictability as
follows. Cancer immunotherapy has been the focus of scientific and medical research conducted
at the highest level for at least 25 years (see Dotti et al. for example, Immunol Rev. 2014,
257(1)1-35). Dotti et al. teaches in the introduction thereof that “[c]himeric antigen receptor-
expressing T (CAR-T) cells are examples of adoptive cellular immunotherapies (ACIs) which
are themselves a subset of complex biological therapies (CBTs) [citations omitted]. While such
therapies have been available for more than 20 years, it has proved difficult to develop them to a
stage at which they can be predictably successful and widely implemented as a standard of care.”
Thus the state of the prior art is considered to be unpredictable with regard to CAR-T
therapy. As it relates to the present invention, it is further emphasized that Dotti et al.
definitively states that predictability has been an issue in the field of cancer immunotherapy
using CAR-T cells.
US Patent Application 20250041417 teaches that despite its potential usefulness as a cancer treatment, adoptive immunotherapy with CAR T cells has been limited, in part, by expression of the endogenous T cell receptor on the cell surface. CAR T cells expressing an endogenous T cell receptor may recognize major and minor histocompatibility antigens following administration to an allogeneic patient, which can lead to the development of graft-versus-host-disease (GVHD). As a result, clinical trials have largely focused on the use of autologous CAR T cells, wherein a patient's T cells are isolated, genetically-modified to incorporate a chimeric antigen receptor, and then re-infused into the same patient. An autologous approach provides immune tolerance to the administered CAR T cells; however, this approach is constrained by both the time and expense necessary to produce patient-specific CAR T cells after a patient's cancer has been diagnosed. ( see entire document, paragraph 0005 in particular)
Thus, Applicant has not provided sufficient guidance to enable one skill in the art to use claimed method of treating any cancer in mammal, comprising administering to the mammal a population of any host cells wherein said host cells comprises a recombinant expression vector comprising a nucleotide sequence encoding a TCR having antigenic specificity for mutant human p53 of SEQ ID :1 and wherein TCRs comprises the amino acid sequences of all of SEQ ID NO: 87-92 in manner reasonably correlated with the scope of the claims.
The scope of the claims must bear a reasonable correlation with the scope of enablement. In re Fisher, 166 USPQ 18(CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Further, the burden of enabling the prevention of a disease (ie. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those humans susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to bronchopulmonary diseases (e.g. neoplasias, bronchogenic cancers, or bronchopulmonary; including HIV infection and AIDS) within the scope of the presently claimed invention. Nor is guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed compounds in preventing these disease states. [ Additionally, the specification fails to enable "treatment" to the extent such treatment includes the prevention of a disease state (e.g. see specification definition on page 9). ] Accordingly, undue experimentation is necessary to determine screening and testing protocols to demonstrate the efficacy of the presently claimed invention.
The scope of the claims must bear a reasonable correlation with the scope of enablement. In re Fisher, 166 USPQ 18(CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
In view of the quantity of experimentation necessary, the unpredictability of the art, the lack of sufficient guidance in the specification, the limited working examples, and the limited amount of direction provided given the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
8. 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.
9. Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 12,479902.
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-35 of U.S. Patent No. 12,479902 recited a method of treating cancer, comprising administering to the patient a host cells expression TCR, comprising amino acid sequences of SEQ ID NO: 87-92.
10. Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,939,365
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-19 of U.S. Patent No. 11,939,365 recited a population of host cells expression TCR, comprising amino acid sequences of SEQ ID NO: 87-92 that are used in the presently claimed methods, and wherein the presently claims methods are disclosed in the specification of U.S. Patent No. 11,939,365.
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
11. Claims 1-19 are provisionally rejected on the grounds of nonstatutory double patenting of the claims of copending Application No. US 20200316121.
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims of copending Application No. US 20200316121 recited a method of treating cancer, comprising administering to the patient a host cells expression TCR, comprising amino acid sequences of SEQ ID NO: 87-92.
This is a provisional nonstatutory double patenting rejection because the conflicting claims have not in fact been patented.
12. Claims 1-19 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims of co-pending Application US 20220332785
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of co-pending Application US 20220332785 are drawn to a population of host cells expression TCR, comprising amino acid sequences of SEQ ID NO: 87-92 that are used in the presently claimed methods, and wherein the presently claims methods are disclosed in the specification of co-pending Application US 20220332785
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
13. No claim is allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michail Belyavskyi whose telephone number is 571/272-0840. The examiner can normally be reached Monday through Friday from 9:00 AM to 5:30 PM. A message may be left on the examiner's voice mail service. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch can be reached on 571/ 272-8149
The fax number for the organization where this application or proceeding is assigned is 571/273-8300
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/MICHAIL A BELYAVSKYI/Primary Examiner, Art Unit 1644
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