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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The present application is a continuation (CON) of application 17/465426, filed 9/2/2021, which is a CON of application 17/372136, filed 9/2/2021, which is a CON of application 17/117191, filed 12/10/2020, which is a CON of application 16/911109, filed 6/24/2020, which is a CON of application 15/881078, filed 1/26/2018, which claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 62/451255, filed 1/27/2017.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(a)-(d) and (f) or under 35 U.S.C. 120, 121, 365(a) or (b), or 386(a) is acknowledged. The present application claims benefit under 35 U.S.C. (119(a)-(d) to foreign application DE102017101671.6, filed 1/27/2017. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The certified copy of the foreign application is provided in application 15/881078.
Status of Claims
Claims 21-40 are pending and are being examined on the merits.
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 21-32 are rejected under 35 U.S.C. 103 as being unpatentable over Simard et al., (from IDS of 3/22/2024, FOR cite No. 2; WO 2004/022709; published 3/18/2004) and Stevanovic et al., (from IDS of 4/7/2023, FOR cite No. 8; WO 2009/138236; published 11/19/2009).
Simard et al. teaches polypeptides, including epitopes, clusters and antigens, as well as compositions comprising the polypeptides and methods of use (abstract). Simard teaches the present invention provides epitopes that have high affinity for MHC I, and that correspond to the processing specificity of the housekeeping proteasome, which is active in peripheral cells, and thus correspond to those (epitopes) presented on target cells; thereby providing an improved method of priming professional antigen presenting cells (APCs) to display accurate target cell epitopes. As such, the use of such epitopes in compositions, such as vaccines or other immunogenic compositions, can activate the cellular immune response to recognize the correctly processed tumor-associated antigen (TAA) and can result in removal of target cells that present such epitopes (pg. 5, lines 24-36).
One such epitope, identified by Simard et al., is PRAME resides 439-448, which is the amino acid sequence of VLYPVPLESY (pgs. 16 and 22, Table 1B, SEQ ID NO: 377). Simard teaches PRAME is a TAA which presents the epitopes of the present invention (pg. 40, lines 4-6). Simard teaches that PRAME was originally observed as a melanoma antigen, and is also expressed in acute myeloid leukemias, (pg. 43, lines 1-3).
Thus, Simard claims a polypeptide epitope of VLYPVPLESY (pg. 147, claim 1), wherein the polypeptide corresponds to an epitope displayed on a tumor cell (claim 14), a composition comprising the polypeptide (claim 18), including a adjuvant, wherein the adjuvant may be a cytokine, CpG, or GM-CSF (claims 21, 23 and 24). Simard also claims an isolated T cell expressing a T cell receptor (TCR) specific for an MHC-peptide complex comprising the polypeptide of claim 1 (claim 40), a pharmaceutical composition comprising the T cell (claim 45), a method of treating comprising administering the composition to an animal (claim 55), for the purpose of eliciting an immune response, diminution of target cells, or loss of mass or size of a tumor (claim 60).
Thus, Simard teaches a peptide consisting of the amino acid sequence VLYPVPLESY, and methods of treating a patient comprising administering T cells that selectively recognize cells which present a peptide comprising the amino acid sequence VLYPVPLESY. However, Simard does not teach wherein the peptide comprising the amino acid sequence VLYPVPLESY is in the form of a pharmaceutically acceptable salt.
Stevanovic et al. teaches peptides, nucleic acids and cells for use in immunotherapy of cancer, including survivin-derived tumor-associated cytotoxic T cells peptide epitopes and tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor responses (abstract). Stevanovic teaches the invention relates peptides of survivin that induce T cells cross-reacting with said peptide, a method of in vitro activation of T lymphocytes comprising contacting the T cells with antigen loaded human class I MHC molecules expressed on the surface of a suitable antigen presenting cell, and administration of the peptides or peptide-specific activated T cells for the treatment of cancer (pg. 8-9, Summary; pg. 95, claims 1-2 and 10-11). Regarding the peptide, Stevanovic teaches pharmaceutical compositions comprise the peptides either in the free form or in the form of a pharmaceutically acceptable salt (pg. 24, para. 5). Stevanovic teaches pharmaceutically acceptable salts are used to render a formulation isotonic (pg. 36, para. 4). Stevanovic teaches a pharmaceutically acceptable salt refers to modifying the peptide by making acid or base salts of the agent, including using organic acids such as acetic acid or inorganic acids like hydrochloric acid (pg. 25, para. 1). Stevanovic teaches “in an especially preferred embodiment the pharmaceutical compositions comprise the peptides as salts of acetic acid (acetates) or hydrochloric acid (chlorides),” (pg. 25, para. 2).
It would have been obvious to one of skill in the art to make the peptide consisting of the amino acid sequence VLYPVPLESY, of Simard, in the form of a pharmaceutically acceptable salt. One would have been motivated to do so given that a salt form of the peptide would support making isotonic solutions comprising the peptide, as taught by Stevanovic. There would have been a reasonable expectation for success given that it is well known in the art how to make acidic or basic salt forms of a peptide, and that salt forms of the peptide are suitable for use in the compositions comprising the peptides, and the methods of activating peptide-specific T cells via peptide presentation in a MHC class I complex on an antigen presenting cell, as taught by Stevanovic et al. Thus the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Thus, the combination of Simard and Stevanovic encompasses a peptide consisting of the amino acid sequence of VLYPVPLESY, in the form of a pharmaceutically acceptable salt, wherein the peptide is used in a method of generating activated T cells, wherein the TCR of the T cells selectively recognizes cells which present the peptide sequence, and methods of treating cancer comprising administering the peptide-specific T cells to a subject in need. Therefore, the combination of Simar and Stevanovic makes obvious the peptide of instant claim 21.
Regarding claim 22, Simard teaches a MHC-peptide complex comprising the polypeptide and a method of activating T cells, in vitro, comprising contacting the T cells with APCs that present the MHC-peptide complex, and therefore makes obvious instant claim 22.
Regarding claims 23-27 and 32, Stevanovic teaches the peptide may be a chloride salt or a acetate salt, and thus makes obvious instant claims 23-24. Simard teaches a composition comprising the peptide, an adjuvant and a pharmaceutically acceptable carrier (pg. 148, claim 18), thus making obvious instant claim 25. Therefore, the combination Simard and Stevanovic makes obvious wherein the composition comprises the peptide in the form of a chloride salt or an acetate salt, of instant claims 26-27. Stevanovic teaches the peptides may also be in compositions which may comprise water and a buffer (pg. 59, para. 5), and thus makes obvious the composition of instant claim 32.
Regarding claims 28-30, Simbard teaches a composition comprising the peptide and an adjuvant, wherein the adjuvant may be CpG, a cytokine, or GM-CSF (Simbard claims 21 and 23-24), and therefore makes obvious instant claim 28. Stevanovic teaches medicaments (i.e. compositions) comprising the peptide and an adjuvant, whereby the adjuvant may be either IL-2 or IL-15 (pg. 57, para. 3 – pg. 58, para. 1). Therefore the combination of Simbard and Stevanovic make obvious instant claims 29-30.
Regarding claim 31, this is a product-by-process claim. MPEP 2113(I) states “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Thus, as the combination of Simbard and Stevanovic make obvious the peptide of instant claim 21, instant claim 31 is also made obvious. Alternatively, Simbard teaches bacterium host cells expressing the construct (Simbard, pg. 149, claims 50 and 52), and therefore makes obvious using a bacteria cell expression system of instant claim 31.
Claims 33-35 and 37-39 are rejected under 35 U.S.C. 103 as being unpatentable over Simard et al., (from IDS of 3/22/2024, FOR cite No. 2; WO 2004/022709; published 3/18/2004).
Simard teaches/claims a polypeptide epitope of VLYPVPLESY (pg. 147, claim 1), wherein the polypeptide corresponds to an epitope displayed on a tumor cell (claim 14), a composition comprising the polypeptide (claim 18), including a adjuvant, wherein the adjuvant may be a cytokine, CpG, or GM-CSF (claims 21, 23 and 24). Simard also claims an isolated T cell expressing a T cell receptor (TCR) specific for an MHC-peptide complex comprising the polypeptide of claim 1 (claim 40), a pharmaceutical composition comprising the T cell (claim 45), a method of treating comprising administering the composition to an animal (claim 55), for the purpose of eliciting an immune response, diminution of target cells, or loss of mass or size of a tumor (claim 60); as described above.
Further, Simard teaches the polypeptide epitope of VLYPVPLESY was derived from PRAME, and that PRAME is a TAA of melanoma and is also expressed in acute myeloid leukemias, (pg. 43, lines 1-3).
Regarding claims 33-35; Simard also teaches/claims a method of treating comprising administering the composition comprising the peptide, or a composition comprising activated T cells expressing a TCR specific for an MHC-peptide complex comprising the peptide (pg. 148, claims 40 and 54-55); and that the methods result in a loss of mass or size of a tumor comprising target cells (pg. 148, claim 60). As the target cells of Simard express the PRAME TAA of melanoma, from which the peptide specificity is derived, it is obvious that the treatment of Simard encompasses treating cancer, wherein the cancer is melanoma. Therefore, Simard makes obvious the method of instant claims 33-34. Simard also teaches the composition comprising the peptide-specific T cells also comprises an adjuvant, which may be CpG, a cytokine or GM-CSF (pg. 148, claims 21 and 23-24, with claims 45, 54-55 and 60). Thus, Simard also makes obvious instant claim 35.
Regarding claims 37-39; Simard also teaches/claims wherein the method of treating, comprising administering a composition comprising the peptide-specific T cells, results in evidence of an immune response (pg. 150, claim 60). Therefore, Simard also makes obvious the methods of eliciting an immune response in a patient with cancer, wherein the cancer is melanoma, of instant claims 37-38; and further comprising a CpG, cytokine or GM-CSF adjuvant of claim 39.
Claims 36 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Simard et al., (from IDS of 3/22/2024, FOR cite No. 2; WO 2004/022709; published 3/18/2004) as applied to claims 33-35 and 37-39 above, and further in view of Stevanovic et al., (from IDS of 4/7/2023, FOR cite No. 8; WO 2009/138236; published 11/19/2009).
Simbard makes obvious methods of treating a tumor or eliciting an immune response in a patient that has melanoma comprising administering a composition of peptide-specific T cells, wherein the T cells target the melanoma PRAME TAA epitope of VLYPVPLESY, and wherein the composition further comprises an adjuvant, which may be a cytokine, as described above. However, Simbard does not explicitly teach that the cytokine adjuvant is IL-2.
Stevanovic teaches the art of medicaments comprising peptide-specific activated T cells, as described above. Stevanovic teaches the medicaments may include an adjuvant. Stevanovic teaches that adjuvants are substances that non-specifically enhance or potentiate the immune response to an antigen and thus would be useful in the medicament of the present invention. Stevanovic teaches the adjuvant may be a cytokine, which may be IL-2 (pg. 57, para. 3).
It would have been obvious to one of skill in the art to add IL-2 as an adjuvant to the compositions of Simbard et al. One would have been motivated to do so given that adjuvants are substances that non-specifically enhance or potentiate the immune response to an antigen, as taught by Stevanovic et al. There would have been a reasonable expectation for success given that cytokines are a suitable adjuvant for use in the invention, as taught by Simbard et al., and that IL-2 is a suitable cytokine, as taught by Stevanovic et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Simbard makes obvious the methods of treating, of instant claims 33-35, and the methods of eliciting an immune response, of instant claims 37-39, as described above. The combination of Simbard and Stevanovic make obvious wherein the adjuvant of the methods is IL-2, and therefore makes obvious instant claims 36 and 40.
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 21-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12 and 18-19 of copending Application No. 18/955,513 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of application ‘513 anticipates that of the instant claims.
Application ‘513 claims a peptide consisting of the amino acid sequence of SEQ ID NO: 402, in the form of a pharmaceutically acceptable salt (claim 1). Application ‘513 SEQ ID NO: 402 is VLYPVPLESY, which is 100% identical to instant SEQ ID NO: 108. Therefore, application ‘513 claim 1 anticipates instant claim 21. Application ‘513 claims 2-9, 12 and 18-19 are identical to instant claims 22-32, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12 and 18-19 of copending Application No. 18/955,513 in view of Simard et al., (from IDS of 3/22/2024, FOR cite No. 2; WO 2004/022709; published 3/18/2004).
The reasons why application ‘513 claims 1-9, 12 and 18-19 anticipate the product of instant claim 21-32 is described above. However, application ‘513 does not claim a method of treating, or eliciting an immune response, in a patient with cancer comprising administering a population of peptide-specific T cells that that target the peptide epitope of instant SEQ ID NO: 108.
Simard teaches/claims a polypeptide epitope of VLYPVPLESY (pg. 147, claim 1; SEQ ID NO: 377 of Table 1B), wherein the polypeptide corresponds to an epitope displayed on a tumor cell (claim 14), a composition comprising the polypeptide (claim 18), including a adjuvant, wherein the adjuvant may be a cytokine, CpG, or GM-CSF (claims 21, 23 and 24). Simard also claims an isolated T cell expressing a T cell receptor (TCR) specific for an MHC-peptide complex comprising the polypeptide of claim 1 (claim 40), a pharmaceutical composition comprising the T cell (claim 45), a method of treating comprising administering the composition to an animal (claim 55), for the purpose of eliciting an immune response, diminution of target cells, or loss of mass or size of a tumor (claim 60); as described above. Further, Simard teaches the polypeptide epitope of VLYPVPLESY was derived from PRAME, and that PRAME is a TAA of melanoma and is also expressed in acute myeloid leukemias, (pg. 43, lines 1-3); therefore making obvious the method for treating, or eliciting an immune response, in a patient with melanoma cancer, as described above.
It would have been obvious to one of skill in the art to utilize the VLYPVPLESY peptide and/or compositions comprising the peptide, of application ‘513 to generate a population of T cells expressing a TCR specific for the VLYPVPLESY peptide epitope, and to use the peptide-specific T cells in a method of treating, or eliciting an immune response, in a patient with melanoma cancer. One would have been motivated to do so in order to generate a cancer therapy. There would have been a reasonable expectation for success given that Simbard teaches the same peptide for use in generating peptide-specific T cells and the administration of the peptide-specific T cells in a method of reducing the tumor size, or eliciting an immune response, in a patient with cancer. Thus the invention as a whole was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 33-35; Simard also teaches/claims a method of treating comprising administering the composition comprising the peptide, or a composition comprising activated T cells expressing a TCR specific for an MHC-peptide complex comprising the peptide (pg. 148, claims 40 and 54-55); and that the methods result in a loss of mass or size of a tumor comprising target cells (pg. 148, claim 60). Therefore, the combination of application ‘513 and Simard makes obvious the method of instant claims 33-34. Simard also teaches the composition comprising the peptide-specific T cells also comprises an adjuvant, which may be CpG, a cytokine or GM-CSF (pg. 148, claims 21 and 23-24, with claims 45, 54-55 and 60). Thus, the combination of application ‘513 and Simard also makes obvious instant claim 35.
Regarding claims 37-39; Simard also teaches/claims wherein the method of treating, comprising administering a composition comprising the peptide-specific T cells, results in evidence of an immune response (pg. 150, claim 60). Therefore, the combination of application ‘513 and Simard also makes obvious the methods of eliciting an immune response in a patient with cancer, wherein the cancer is melanoma, of instant claims 37-38; and further comprising a CpG, cytokine or GM-CSF adjuvant of claim 39.
Regarding claims 36 and 40, application ‘513 claims a composition comprising the peptide and an adjuvant, wherein the adjuvant is IL-2 (claims 8-9) and Simard teaches administering an adjuvant, wherein the adjuvant is a cytokine. Therefore the combination of application ‘513 and Simard make obvious wherein the adjuvant is IL-2, of instant claims 36 and 40.
This is a provisional nonstatutory double patenting rejection.
It is noted that the claimed peptide constitutes a fragment of a naturally occurring protein. However, the claimed limitation that the peptide is in the form of a pharmaceutically acceptable salt distinguishes the claimed peptides from those occurring in nature since it provides a markedly different characteristic (see parent application 17/465,426 and the declaration of Dr. Stern in applicant’s remarks, filed 12/8/2023).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel E. Kolker can be reached at (571) 272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644