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 and 30-69 are pending.
Claims 1 and 30-69 are under examination on the merits.
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. Claims 1 and 30-69 have an effective filing date of 11/20/2015, corresponding to PRO 62/258,134.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/28/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly the information disclosure statement is being considered by the examiner.
Claim Rejections
35 U.S.C. 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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 30-39, 41-53, 55-67, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Scheinberg et al. (US PG PUB 2010/0092522, publication date: 05/06/2010, IDS), in view of Freeman et al. (US PUB 2015/0210769, publication date: 07/30/2015).
Scheinberg et al. teach a method of treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer, and inducing an immune response against a WT1-expressing cancer, the method comprising administering to said subject a vaccine comprising an isolated WT1 peptide, wherein said WT1 peptide comprises the amino acid sequence of SGQAYMFPNAPYLPSCLES (SEQ ID NO: 41), RSDELVRHHNMHQRNMTKL (SEQ ID NO: 2), or PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO): 4), and an adjuvant, such as QS21, and/or carrier. See [0003] - [0009], [0125], and [0126]. At Table 1, Scheinberg et al. teach the WT1 analog peptide of YMFPNAPYL (SEQ ID NO: 6). It is noted that SEQ ID NO(s): 41, 2, 4, and 6 of Scheinberg et al. share 100% sequence homology with the instant SEQ ID NO(s): 125, 1, 2, and 124, respectively.
Scheinberg et al. further teach a method of inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer, the method comprising administering to said subject a vaccine comprising an isolated WT1 peptide, wherein said WT1 peptide comprises the amino acid sequence of RSDELVRHHNMHQRNMTKL (SEQ ID NO: 2) or PGCNKRYFKLSHLQMHSRKHTG. (SEQ ID NO: 4), and an adjuvant or carrier, thereby inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer see claims 64, 74, and 79. At [0159], Scheinberg et al. teach that methods of the invention may be used to treat various WT-1 expressing cancers, such as ovarian cancer and mesothelioma.
As such Scheinberg et al. teach a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof at least one WT1 peptide against a WT1-expressing cancer, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125). Scheinberg et al. do not teach a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125). This deficiency is remedied by Freeman et al.
At [0452] - [0455], Freeman et al. teach the treatment of cancer, such as ovarian cancer or mesothelioma, by administering to a subject in need thereof an anti-PD-1 antibody. At [0518], Freeman et al. provide examples of different therapeutic anti-PD-1 antibodies including pembrolizumab and nivolumab.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Scheinberg et al. with the teachings of Freeman et al. to develop a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125). One of ordinary skill in the art would have been motivated to do so, because Scheinberg et al. teach a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, such as a WT1-expressing ovarian cancer, comprising administering to a human subject in need thereof a) at least one WT1 peptide against a WT1-expressing cancer, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125) and b) an adjuvant, such as QS21. Furthermore Freeman et al. teach the treatment of cancer, such as ovarian cancer or mesothelioma, by administering to a subject in need thereof an anti-PD-1 antibody, such as pembrolizumab and nivolumab. One of ordinary skill in the art would have therefore been motivated to modify the method of Scheinberg et al. to comprise the administration of pembrolizumab or nivolumab, because the resultant method would be expected to treat WT1-expressing ovarian cancers or WT1-expressing mesothelioma by 1) inducing an immune response, such as an antigen-specific CD8+ T cell response and CD4+ T cell response, against said WT1-expressing ovarian cancer (or mesothelioma) via the action of a WT1 immunogenic peptide and 2) blocking the engagement of PD-1 expressed on said antigen-specific T cells by PD-1 ligands via the action of pembrolizumab or nivolumab, thereby blocking PD-1-mediated T cell inhibition. The invention of Scheinberg et al. and Freeman et al. meets the limitations of claims 1, 30-33, 35, 36, 41-47, 49, 50, 55-61, 63, 64, 69.
With respect to claims 34, 37, 48, 51, 62, and 65, at [0129], Scheinberg et al. teach that “a composition or vaccine of methods and compositions of the present invention further comprises an adjuvant. In another embodiment, the adjuvant is Montanide ISA 51. Montanide ISA 51 contains a natural metabolizable oil and a refined emulsifier.” At [0205], Scheinberg et al. teach that formulations of the invention may be administered subcutaneously or intravenously. With respect to the dosages and administration schedules of the claimed WT1 peptides and checkpoint inhibitor antibodies, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation, which states that:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, drug dosages and administration schedules, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed drug dosages and administration schedules are akin to the variables discussed in the cited MPEP passage, because said drug dosages and administration schedules are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed drug dosages and administration schedules, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to different drug dosages and administration schedules, and these variables achieve a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited drug dosages and administration schedules are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a cancer patient, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable range of said variables, the drug dosages and administration schedules recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claims 38, 39, 52, 53, 66, and 67, at [0144], Freeman et al. state that treatment with an anti-PD-1 antibody may occur in a subject that is undergoing chemotherapy or has undergone chemotherapy. One of ordinary skill in the art would have been motivated to determine whether the invention of Scheinberg et al. and Freeman et al. provides a more desirable therapeutic benefit when administered either during or following chemotherapy. Furthermore the invention of Scheinberg et al. and Freeman et al. would be expected to generate an immune response, i.e., therapeutic benefit, when administered to subject suffering from effectively any type of WT1-expressing cancer, including WT1-expressing malignant pleural mesothelioma.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claims 40, 54, and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Scheinberg et al. (US PG PUB 2010/0111986, publication date: 05/06/2010, IDS) and Freeman et al. (US PUB 2015/0210769, publication date: 07/30/2015), as applied to claims 1, 30-39, 41-53, 55-67, and 69, and further in view of and Scheinberg et al. (US PAT 7,598,221, issue date: 10/06/2009, hereafter referred to as Scheinberg II, IDS).
As indicated above one of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Scheinberg et al. with the teachings of Freeman et al. to develop a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125). These references do not teach or suggest a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125), wherein the subject is in remission. This deficiency is remedied by Scheinberg II.
Scheinberg II teach that “synthetic [WT1] peptides or analogue segments thereof described herein may be used to activate T-cells ex vivo or in vivo. In vivo, the synthetic peptides or analogue segments thereof or DNA encoding the same may be administered to a patient or to a healthy donor to induce cytotoxic T-cells If administered to a donor these cytotoxic T-cells are obtained from the donor and infused into an individual in need of them, such as an individual with an active cancer, in remission from a cancer or at risk for developing a cancer.” See column 14.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Scheinberg et and Freeman et al. with those of Scheinberg II to develop a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125), wherein the subject is in remission. One of ordinary skill in the art would have been motivated to do so, because Scheinberg et and Freeman et al. teach or suggest a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1 or PD-L1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125). Furthermore as indicated above Scheinberg II teach that WT1 peptides may be administered to individuals in remission from a cancer. One of ordinary skill in the art would have been motivated to perform the method of Scheinberg et al. and Freeman et al. on individuals having WT1-expressing cancers that are in remission, because the method of Scheinberg et al. and Freeman et al. would have reasonably been expected to induce an immune response directed to said WT1-expressing cancer, because the WT1 peptides would be expected to elicit the proliferation of WT1-specific T cell responses. Furthermore the checkpoint inhibitor nivolumab would block the engagement of PD-1 expressed on said WT1-specific T cells by PD-1 ligands, thereby blocking PD-1-mediated T cell inhibition. Said WT1-specific T cell would be useful in eliminating residual cancer cells in the patient in remission, and WT1- specific T cell may ameliorate the effects of recurrence.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Nonstatutory 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 1 and 30-69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,033,613.
Although the claims at issue are not identical, they are not patentably distinct from each other, because both sets of claims recite a method for treating, reducing the incidence of, or inducing an immune response against a WT1-expressing cancer, comprising administering to a human subject in need thereof (a) at least one WT1 peptide against a WT1-expressing cancer, and (b) at least one antibody checkpoint inhibitor that blocks or inhibits PD-1, wherein the at least one WT1 peptide is a combination of YMFPNAPYL (SEQ ID NO:124), RSDELVRHHNMHQRNMTKL (SEQ ID NO:1), PGCNKRYFKLSHLQMHSRKHTG (SEQ ID NO: 2) and SGQAYMFPNAPYLPSCLES (SEQ ID NO: 125).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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