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
Applicant’s election without traverse of Group I (claims 1-24, 27-31, and 36-46), as well as the species election of 1) a single anti-PD-1 antibody species (an anti-PD-1 antibody comprising the HCDRs 1-3 and the LCDRs 1-3 of SEQ ID NO(s): 3-8, respectively) and 2) a single anti-CTLA4 antibody species (ipilimumab) in the reply filed on 09/29/2025 is acknowledged.
Claims 1-24, 27-31, 36-46, and 48 are pending.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/29/2025.
Claims 27 and 37-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/29/2025.
Claims 1-24, 28-31, 36, and 41-46 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 1-24, 28-31, 36, and 41-46 have an effective filing date of 07/19/2021, corresponding to PRO 63/223,281.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/18/2022, 03/17/2023, and 06/30/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are 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 (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.
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 1-4, 6-24, 36, and 41-46 are rejected under 35 U.S.C. 103 as being unpatentable over Lala et al. (WO 2019/160755, international filing date: 02/08/2019) in view of Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as evidenced by Russell et al. (U.S. PAT 9,428,736, issue date: 08/30/2016).
At p. 1, lines 6-10, Lala et al. teach the treatment of cancer by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. At p. 26, lines 14-17, Lala et al. teach that anti-PD-1 antibodies may be used in the treatment of non-small cell lung carcinoma (NSCLC). At p. 21, Lala et al. teach the anti-CTLA4 antibody ipilimumab.
Based upon the teachings of Lala et al., one of ordinary skill in the art would have been motivated to treat various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Lala et al. do not teach a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as vesicular stomatitis virus (VSV), in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. This deficiency is remedied by Sznol et al.
Sznol et al. teach that “VV1 is an oncolytic vesicular stomatitis virus engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity, and the human sodium iodide symporter (NIS) for virus tracking by SPECT imaging. Cancer cells are often hyporesponsive to IFNβ, enabling the efficient spread of VV1 and resulting in increased oncolysis. Differently from other oncolytic viruses, VV1 is suitable for both intra-tumoral (IT) and/or intra-venous (IV) administration. Despite considerable anti-tumor activity with checkpoint inhibitors (CPI) among some malignancies, long term survival and overall cures remain elusive. Prior Ph 1 studies have shown significant anti-tumor activity among several malignancies when VV1 was administered either as monotherapy or in combination with a CPI, despite progression on prior CPI monotherapy. Furthermore, pre- and post-treatment biopsy evaluations after VV1 treatment have demonstrated T cell infiltration and inflammation in both IT injected and non-injected lesions. Among IV treated patients (pts), IFNβ was detectable in the serum correlating with viral replication, making it an effective biomarker. C is a high-affinity potent human IgG4 anti-PD-1 monoclonal antibody. Though approved for use in cutaneous squamous cell carcinoma, C has shown anti-tumor activity, similar to other CPI, in several other indications. Therefore, VV1 and C could be an attractive combination for the immunotherapy for several solid tumors. This study represents the first clinical evaluation of VV1 in combination with C in pts with advanced solid tumors. Methods: The Ph 2 Simon 2 stage five-arm study of IV administration VV1 in combination with IV C will enroll pts with advanced NSCLC, HCC, melanoma & endometrial cancer.”
Based upon the teachings of Sznol et al., one of ordinary skill in the art would have been motivated to treat various types of solid tumors, such as NSCLC, by administering immunotherapy comprising a combination of VV1 (Voyager V1, an oncolytic VSV engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity) and an anti-PD-1 antibody to a subject in need thereof, because there would have been a reasonable expectation that said immunotherapy would provide a therapeutic benefit to said subject.
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 Lala et al. and Sznol et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. One of ordinary skill in the art would have been motivated to do so, because Lala et al. teach a method of treating various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Furthermore Sznol et al. teach or suggest the treatment of cancers, such as NSCLC, by administering an anti-PD-1 antibody in combination with Voyager V1, an oncolytic VSV engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity, and an anti-PD-1 antibody. As such one of ordinary skill in the art would have been motivated to modify the method of Lala et al. to comprise the administration of Voyager V1, as taught by Sznol et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as NSCLC, by combining the administration of multiple anti-cancer medicaments. The invention of Lala et al. and Sznol et al. meets the limitations of claim 1.
At [065] of the specification, it is indicated that Voyager V1 is described by Russell et al. As evidenced by Fig. 1 of Russell et al. Voyager V1 is a recombinant VSV that includes an IFNβ sequence positioned between the viral M and G genes and a human sodium iodide symporter (NIS) sequence positioned between the viral G and L genes. As such Voyager V1 meets the limitations of an oncolytic VSV that expresses a cytokine (IFNβ), which is positioned between the viral M and G genes, and NIS, which is positioned between the viral M and G genes, thus meeting the limitations of claims 2-4 and 6-11.
With respect to claims 12 and 13, one of ordinary skill in the art would appreciate that when administering a combination of medicaments, said medicaments may be administered concurrently or sequentially, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy.
With respect to claims 14 and 15, one of ordinary skill in the art would appreciate that the claimed CTLA4 inhibitor may be administered either as a single dose or in multiple doses, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy. Furthermore these claims recite functional language, specifically that the single dose administration of a CTLA4 inhibitor results in anti-tumor efficacy (characterized by a decrease in mean or average tumor volume, percent survival, numbers of tumor free patients in each treatment group, or a combination thereof) that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. The limitation connected to the recited functional language is the administration of a single dose of a CTLA4 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of a single dose of a CTLA4 inhibitor. One of ordinary skill in the art would understand that the intended result flows from the administration of a single dose of a CTLA4 inhibitor, i.e., the administration of a single dose of a CTLA4 inhibitor would be expected to result in tumor efficacy that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. As such the claimed functional language does not distinguish the instant invention from that of Lala et al. and Sznol et al.
With respect to the oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses recited in claims 16-21, 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 doses, 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 medicament doses are akin to the variables discussed in the cited MPEP passage, because said medicament doses are an optimizable variable that would affect at least efficacy and safety. 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 medicament doses, because such optimization would produce a more effective/safer 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 oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses, and these variables achieve a recognized result, such as drug efficacy and/or drug toxicity. Accordingly the recited medicament doses are result-effective variables that achieve a recognized result, such as drug efficacy and/or drug toxicity, and it is submitted that since one of ordinary skill in the art would have been motivated to determine the optimum or workable ranges of said variables, the recited medicament doses were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claim 22, Sznol et al. teach that Voyager V1 is administered intravenously (IV).
With respect to claim 23, at p. 34, lines 3-8, Lala et al. teach that anti-PD-1 and anti-CTLA4 antibodies may be administered via IV infusion.
With respect to claim 24, as indicated above, the invention of Lala et al. and Sznol et al. may be used to treat NSCLC, a type of lung cancer.
With respect to claim 36, at p. 21, Lala et al. teach the anti-CTLA4 antibody ipilimumab.
With respect to claims 41-44, these claims recite functional language, specifically that the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody results in a delay in tumor growth (or tumor inhibition). The limitations connected to the recited functional language is the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody. One of ordinary skill in the art would understand that the intended result flows from the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, i.e., the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody would be expected to result in a delay in tumor growth (or tumor inhibition). As such the claimed functional language does not distinguish the instant invention from that of Lala et al. and Sznol et al.
With respect to claims 45 and 46, at p. 34, lines 25-27, Lala et al. teach that an anti-PD-1 antibody and an anti-CTLA4 antibody may be administered in combination with an additional therapeutic agent, such as an anti-LAG3 antibody.
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 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Lala et al. (WO 2019/160755, international filing date: 02/08/2019) in view of Silverman et al. (US PG PUB 20130071432, publication date 03/21/2013).
As indicated above based upon the teachings of Lala et al., one of ordinary skill in the art would have been motivated to treat various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Lala et al. do not teach a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as attenuated VSV strain M51R, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. This deficiency is remedied by Silverman et al.
At the Abstract Silverman et al. teach that the combination of an oncolytic virus in combination with an immunomodulatory agent in the treatment of cancer. At [0043], Silverman et al. teach that the invention may be used to treat lung cancer. At [0052], Silverman et al. teach that the oncolytic virus may be VSV. At [0083], Silverman et al. teach that “ACHN human renal cell carcinoma cells were implanted s.c. into nude mice (FIG. 2C). An attenuated VSV strain (M51R), which triggers a higher interferon response than wild type VSV and may have an improved safety profile compared with wild type VSV, was used… Direct inoculation of VSV M51R into the ACHN tumors or orally delivered sunitinib alone retarded tumor growth, whereas the combined treatment caused complete regression of the ACHN tumors (FIG. 2C). The mice were considered cured because the tumors did not reappear, even 6 weeks after sunitinib treatment ceased.”
Based upon the teachings of Silverman et al., one of ordinary skill in the art would have been motivated to administer attenuated VSV strain M51R in combination with an immunomodulatory agent in the treatment of cancer.
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 Lala et al. and Silverman et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as attenuated VSV strain M51R, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. One of ordinary skill in the art would have been motivated to do so, because Lala et al. teach a method of treating various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Furthermore based upon the teachings of Silverman et al., one of ordinary skill in the art would have been motivated to administer attenuated VSV strain M51R in combination with an immunomodulatory agent in the treatment of cancer. As such one of ordinary skill in the art would have been motivated to modify the method of Lala et al. to comprise the administration of attenuated VSV strain M51R, as taught by Silverman et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as lung cancer, by combining the administration of multiple anti-cancer medicaments. The invention of Lala et al. and Silverman et al. meets the limitations of claims 1 and 5.
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 28-31 are rejected under 35 U.S.C. 103 as being unpatentable over Lala et al. (WO 2019/160755, international filing date: 02/08/2019) in view of Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as evidenced by Russell et al. (U.S. PAT 9,428,736, issue date: 08/30/2016), as applied to claims 1-4, 6-24, 36, and 41-46, and further in view of Papadopoulos et al. (US PAT 9,987,500, issue date: 06/05/2018).
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 Lala et al. and Sznol et al. to develop a method of treating cancer by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. These references do not teach or suggest an anti-PD-1 antibody that comprises the instant SEQ ID NO(s): 9 and 10. This deficiency is remedied by Papadopoulos et al.
At the Abstract, Papadopoulos et al. teach that “[t]he present invention provides antibodies that bind to the T-cell co-inhibitor programmed death-1 (PD-1) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to PD-1. In certain embodiments, the present invention provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-1 and a second binding specificity that binds to an autoimmune tissue antigen, another T-cell co-inhibitor, an Fc receptor, or a T-cell receptor. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing PD-1 activity, thus providing a means of treating a disease or disorder such as cancer or a chronic viral infection.” At Table 3, Papadopoulos et al. teach anti-PD-1 antibody H4H7798N, which comprises the heavy and light chains of SEQ ID NO(s): 330 and 331, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively. At Table 6, it is demonstrated that anti-PD-1 antibody H4H7798N effectively blocks the binding of PD-L1 to PD-1.
Based upon the teachings of Papadopoulos et al., one of ordinary skill in the art would have been motivated to administer anti-PD-1 antibody H4H7798N to cancer patients, because there would have been a reasonable expectation that such a method would provide a therapeutic benefit to said patients.
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 Lala et al. and Sznol et al. with the teachings of Papadopoulos et al. to develop a method of treating cancer by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody is H4H7798N. One of ordinary skill in the art would have been motivated to do so, because Lala et al. and Sznol et al. teach or suggest a method of treating cancer by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Furthermore based upon the teachings of Papadopoulos et al., one of ordinary skill in the art would have been motivated to administer anti-PD-1 antibody H4H7798N to cancer patients, because there would have been a reasonable expectation that such a method would provide a therapeutic benefit to said patients. As such one of ordinary skill in the art would have been motivated to modify the method of Lala et al. and Sznol et al. to comprise the administration of anti-PD-1 antibody H4H7798N, because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers by combining the administration of multiple anti-cancer medicaments. The invention of Lala et al., Sznol et al., and Papadopoulos et al. meets the limitations of claims 1 and 28-31.
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 1-4, 6-24, and 41-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 12,024,570 and 2) claim 1 of U.S. Patent No. 10,844,137 in view of Lala et al. (WO 2019/160755, international filing date: 02/08/2019) and Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as evidenced by Russell et al. (U.S. PAT 9,428,736, issue date: 08/30/2016).
Conflicting claim 1 recites an anti-CTLA-4 antibody.
The teachings of Lala et al. and Sznol et al. are detailed 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 conflicting claims with the teachings of Lala et al. and Sznol et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. One of ordinary skill in the art would have been motivated to do so, because conflicting claim 1 recites an anti-CTLA-4 antibody. Furthermore Lala et al. teach a method of treating various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, and Sznol et al. teach or suggest the treatment of cancers, such as NSCLC, by administering an anti-PD-1 antibody in combination with Voyager V1, an oncolytic VSV engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity, and an anti-PD-1 antibody. As such one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of an anti-PD-1 antibody, as taught by Lala et al., and to comprise the administration of Voyager V1, as taught by Sznol et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as NSCLC, by combining the administration of multiple anti-cancer medicaments. The invention of the conflicting claims, Lala et al., and Sznol et al. meets the limitations of claim 1.
At [065] of the specification, it is indicated that Voyager V1 is described by Russell et al. As evidenced by Fig. 1 of Russell et al. Voyager V1 is a recombinant VSV that includes an IFNβ sequence positioned between the viral M and G genes and a human sodium iodide symporter (NIS) sequence positioned between the viral G and L genes. As such Voyager V1 meets the limitations of an oncolytic VSV that expresses a cytokine (IFNβ), which is positioned between the viral M and G genes, and NIS, which is positioned between the viral M and G genes, thus meeting the limitations of claims 2-4 and 6-11.
With respect to claims 12 and 13, one of ordinary skill in the art would appreciate that when administering a combination of medicaments, said medicaments may be administered concurrently or sequentially, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy.
With respect to claims 14 and 15, one of ordinary skill in the art would appreciate that the claimed CTLA4 inhibitor may be administered either as a single dose or in multiple doses, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy. Furthermore these claims recite functional language, specifically that the single dose administration of a CTLA4 inhibitor results in anti-tumor efficacy (characterized by a decrease in mean or average tumor volume, percent survival, numbers of tumor free patients in each treatment group, or a combination thereof) that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. The limitation connected to the recited functional language is the administration of a single dose of a CTLA4 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of a single dose of a CTLA4 inhibitor. One of ordinary skill in the art would understand that the intended result flows from the administration of a single dose of a CTLA4 inhibitor, i.e., the administration of a single dose of a CTLA4 inhibitor would be expected to result in tumor efficacy that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. As such the claimed functional language does not distinguish the instant invention from that of the conflicting claims, Lala et al., and Sznol et al.
With respect to the oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses recited in claims 16-21, 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 doses, 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 medicament doses are akin to the variables discussed in the cited MPEP passage, because said medicament doses are an optimizable variable that would affect at least efficacy and safety. 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 medicament doses, because such optimization would produce a more effective/safer 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 oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses, and these variables achieve a recognized result, such as drug efficacy and/or drug toxicity. Accordingly the recited medicament doses are result-effective variables that achieve a recognized result, such as drug efficacy and/or drug toxicity, and it is submitted that since one of ordinary skill in the art would have been motivated to determine the optimum or workable ranges of said variables, the recited medicament doses were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claim 22, Sznol et al. teach that Voyager V1 is administered intravenously (IV).
With respect to claim 23, at p. 34, lines 3-8, Lala et al. teach that anti-PD-1 and anti-CTLA4 antibodies may be administered via IV infusion.
With respect to claim 24, as indicated above, the invention of the conflicting claims, Lala et al., and Sznol et al. may be used to treat NSCLC, a type of lung cancer.
With respect to claims 41-44, these claims recite functional language, specifically that the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody results in a delay in tumor growth (or tumor inhibition). The limitations connected to the recited functional language is the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody. One of ordinary skill in the art would understand that the intended result flows from the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, i.e., the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody would be expected to result in a delay in tumor growth (or tumor inhibition). As such the claimed functional language does not distinguish the instant invention from that of the conflicting claims, Lala et al., and Sznol et al.
With respect to claims 45 and 46, at p. 34, lines 25-27, Lala et al. teach that an anti-PD-1 antibody and an anti-CTLA4 antibody may be administered in combination with an additional therapeutic agent, such as an anti-LAG3 antibody.
Therefore the claims are prima facie obvious over the conflicting claims in view of the references cited.
Claims 1 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 12,024,570 and 2) claim 1 of U.S. Patent No. 10,844,137 in view of Lala et al. (WO 2019/160755, international filing date: 02/08/2019) and Silverman et al. (US PG PUB 20130071432, publication date 03/21/2013).
Conflicting claim 1 recites an anti-CTLA-4 antibody.
The teachings of Lala et al. and Silverman et al. are detailed 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 conflicting claims with the teachings of Lala et al. and Silverman et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as attenuated VSV strain M51R, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. One of ordinary skill in the art would have been motivated to do so, because conflicting claim 1 recites an anti-CTLA-4 antibody. Furthermore Lala et al. teach a method of treating various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. Based upon the teachings of Silverman et al., one of ordinary skill in the art would have been motivated to administer attenuated VSV strain M51R in combination with an immunomodulatory agent in the treatment of cancer. As such one of ordinary skill in the art would have been motivated to modify the method of the conflicting claims and Lala et al. to comprise the administration of attenuated VSV strain M51R, as taught by Silverman et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as lung cancer, by combining the administration of multiple anti-cancer medicaments.
Claims 28-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 12,024,570 and 2) claim 1 of U.S. Patent No. 10,844,137 in view of Lala et al. (WO 2019/160755, international filing date: 02/08/2019) and Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as applied to claims 1-4, 6-24, and 41-46, and further in view of Papadopoulos et al. (US PAT 9,987,500, issue date: 06/05/2018).
Conflicting claim 1 recites an anti-CTLA-4 antibody.
The teachings of Lala et al., Sznol et al., and Papadopoulos et al. are detailed 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 conflicting claims with the teachings of Lala et al., Sznol et al., and Papadopoulos et al. to develop a method of treating cancer by administering an oncolytic virus, such as VSV, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody is H4H7798N. One of ordinary skill in the art would have been motivated to do so, because conflicting claim 1 recites an anti-CTLA-4 antibody. Furthermore Lala et al. teach a method of treating various cancers, including NSCLC, by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, and Sznol et al. teach or suggest the treatment of cancers, such as NSCLC, by administering an anti-PD-1 antibody in combination with Voyager V1, an oncolytic VSV engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity, and an anti-PD-1 antibody. As such one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of an anti-PD-1 antibody, as taught by Lala et al., and to comprise the administration of Voyager V1, as taught by Sznol et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as NSCLC, by combining the administration of multiple anti-cancer medicaments. Additionally based upon the teachings of Papadopoulos et al., one of ordinary skill in the art would have been motivated to administer anti-PD-1 antibody H4H7798N to cancer patients, because there would have been a reasonable expectation that such a method would provide a therapeutic benefit to said patients.
Claims 1-4, 6-24, 28-31, and 41-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 22, 23, 25, and 32 of U.S. App. No. 18/425,027 in view of Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as evidenced by Russell et al. (U.S. PAT 9,428,736, issue date: 08/30/2016).
Conflicting claims 7, 23, 25, and 32 recite a method of treating NSCLC by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively.
The teachings of Sznol et al. are detailed 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 conflicting claims with the teachings of Sznol et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as VSV (Voyager V1), an anti-PD-1 antibody, and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively. One of ordinary skill in the art would have been motivated to do so, because the conflicting claims recite a method of treating NSCLC by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively. Furthermore Sznol et al. teach or suggest the treatment of cancers, such as NSCLC, by administering an anti-PD-1 antibody in combination with Voyager V1, an oncolytic VSV engineered to express human IFNβ to enhance cellular anti-tumor immune responses and tumor selectivity, and an anti-PD-1 antibody. As such one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of Voyager V1, as taught by Sznol et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as NSCLC, by combining the administration of multiple anti-cancer medicaments. The invention of the conflicting claims and Sznol et al. meets the limitations of claim 1 and 28-31.
At [065] of the specification, it is indicated that Voyager V1 is described by Russell et al. As evidenced by Fig. 1 of Russell et al. Voyager V1 is a recombinant VSV that includes an IFNβ sequence positioned between the viral M and G genes and a human sodium iodide symporter (NIS) sequence positioned between the viral G and L genes. As such Voyager V1 meets the limitations of an oncolytic VSV that expresses a cytokine (IFNβ), which is positioned between the viral M and G genes, and NIS, which is positioned between the viral M and G genes, thus meeting the limitations of claims 2-4 and 6-11.
With respect to claims 12 and 13, one of ordinary skill in the art would appreciate that when administering a combination of medicaments, said medicaments may be administered concurrently or sequentially, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy.
With respect to claims 14 and 15, one of ordinary skill in the art would appreciate that the claimed CTLA4 inhibitor may be administered either as a single dose or in multiple doses, and one of ordinary skill in the art would have been motivated to determine which administration regimen results in safe and efficacious therapy. Furthermore these claims recite functional language, specifically that the single dose administration of a CTLA4 inhibitor results in anti-tumor efficacy (characterized by a decrease in mean or average tumor volume, percent survival, numbers of tumor free patients in each treatment group, or a combination thereof) that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. The limitation connected to the recited functional language is the administration of a single dose of a CTLA4 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of a single dose of a CTLA4 inhibitor. One of ordinary skill in the art would understand that the intended result flows from the administration of a single dose of a CTLA4 inhibitor, i.e., the administration of a single dose of a CTLA4 inhibitor would be expected to result in tumor efficacy that is comparable to a combination therapy that comprises two or more doses of the CTLA4 inhibitor. As such the claimed functional language does not distinguish the instant invention from that of the conflicting claims and Sznol et al.
With respect to the oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses recited in claims 16-21, 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 doses, 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 medicament doses are akin to the variables discussed in the cited MPEP passage, because said medicament doses are an optimizable variable that would affect at least efficacy and safety. 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 medicament doses, because such optimization would produce a more effective/safer 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 oncolytic virus, PD-1 inhibitor, and CTLA4 inhibitor doses, and these variables achieve a recognized result, such as drug efficacy and/or drug toxicity. Accordingly the recited medicament doses are result-effective variables that achieve a recognized result, such as drug efficacy and/or drug toxicity, and it is submitted that since one of ordinary skill in the art would have been motivated to determine the optimum or workable ranges of said variables, the recited medicament doses were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention.
With respect to claim 22, Sznol et al. teach that Voyager V1 is administered intravenously (IV).
With respect to claim 23, conflicting claim 22 recites the IV administration of antibodies.
With respect to claim 24, as indicated above, the invention of the conflicting claims and Sznol et al. may be used to treat NSCLC, a type of lung cancer.
With respect to claims 41-44, these claims recite functional language, specifically that the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody results in a delay in tumor growth (or tumor inhibition). The limitations connected to the recited functional language is the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody. One of ordinary skill in the art would understand that the intended result flows from the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody, i.e., the administration of an oncolytic virus, an anti-PD-1 antibody, and an anti-CTLA4 antibody would be expected to result in a delay in tumor growth (or tumor inhibition). As such the claimed functional language does not distinguish the instant invention from that of the conflicting claims and Sznol et al.
With respect to claims 45 and 46, conflicting claim 23 recites various additional therapeutic agents that may be administered in combination with an anti-PD-1 antibody.
Therefore the claims are prima facie obvious over the conflicting claims in view of the references cited.
This is a provisional nonstatutory double patenting rejection.
Claim 36 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 22, 23, 25, and 32 of U.S. App. No. 18/425,027 in view of Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), as evidenced by Russell et al. (U.S. PAT 9,428,736, issue date: 08/30/2016), as applied to claims 1-4, 6-24, 28-31, and 41-46, and further in view of Lala et al. (WO 2019/160755, international filing date: 02/08/2019).
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 conflicting claims with the teachings of Sznol et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as VSV (Voyager V1), an anti-PD-1 antibody, and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively.
The teachings of Lala et al. are detailed 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 conflicting claims with the teachings of Sznol et al. and Lala et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as VSV (Voyager V1), an anti-PD-1 antibody, and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively, and wherein said anti-CTLA4 antibody is ipilimumab. As indicated above Lala et al. teach the anti-CTLA4 antibody ipilimumab. One of ordinary skill in the art would be motivated to modify the invention of the conflicting claims and Sznol et al. to comprise the administration of the anti-CTLA4 antibody ipilimumab, because there would have been a reasonable expectation that such a method would provide a therapeutic benefit to NSCLC patients.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 22, 23, 25, and 32 of U.S. App. No. 18/425,027 in view of Silverman et al. (US PG PUB 20130071432, publication date 03/21/2013).
Conflicting claims 7, 23, 25, and 32 recite a method of treating NSCLC by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively.
The teachings of Silverman et al. are detailed 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 conflicting claims with the teachings of Silverman et al. to develop a method of treating cancer, such as NSCLC by administering an oncolytic virus, such as attenuated VSV strain M51R, in combination with an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof. One of ordinary skill in the art would have been motivated to do so, because the conflicting claims recite a method of treating NSCLC by administering an anti-PD-1 antibody and an anti-CTLA4 antibody to a subject in need thereof, wherein said anti-PD-1 antibody comprises the heavy and light chains of SEQ ID NO(s): 9 and 10, respectively, which share 100% sequence homology with the instant SEQ ID NO(s): 9 and 10, respectively. SEQ ID NO: 9 comprises the instant SEQ ID NO: 1, which comprises the HCDRs 1-3 of SEQ ID NO(s): 3-5, respectively. SEQ ID NO: 10 comprises the instant SEQ ID NO: 2, which comprises the LCDRs 1-3 of SEQ ID NO(s): 6-8, respectively. Furthermore based upon the teachings of Silverman et al., one of ordinary skill in the art would have been motivated to administer attenuated VSV strain M51R in combination with an immunomodulatory agent in the treatment of cancer. As such one of ordinary skill in the art would have been motivated to modify the method of the conflicting claims to comprise the administration of attenuated VSV strain M51R, as taught by Silverman et al., because there would have been a reasonable expectation the resultant invention would be effective in treating various cancers, such as lung cancer, by combining the administration of multiple anti-cancer medicaments.
This is a provisional nonstatutory double patenting rejection.
Similarly, claims 1-24, 28-31, 36, and 41-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over the pertinent claims of the below listed U.S. Patent Nos. in view of the references cited in the rejection of the claims under 35 U.S.C. 103, specifically, Lala et al. (WO 2019/160755, international filing date: 02/08/2019), Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), Silverman et al. (US PG PUB 20130071432, publication date 03/21/2013), and Papadopoulos et al. (US PAT 9,987,500, issue date: 06/05/2018).
Patent No.
Brief Description of the Invention
Pertinent Claims
11,292,842
ANTI-PD-1 ANTIBODIES FOR TREATMENT OF LUNG CANCER
1, 16, 18, 22, and 23
11,932,692
METHODS OF TREATING CANCER PAIN BY ADMINISTERING A PD-1 INHIBITOR
1 and 13-18
12,473,364
INTRALESIONAL ADMINISTRATION OF PD-1 INHIBITORS FOR TREATING SKIN CANCER
1
10,737,113
HUMAN ANTIBODIES TO PD-1
1
10,457,725
METHODS OF TREATING SKIN CANCER BY ADMINISTERING A PD-1 INHIBITOR
1 and 13-18
The instant claims are rendered obvious by the combined teachings of the prior art above as discussed in the 103 section, the 103s being incorporated here.
It is noted that all of the conflicting patents are generally drawn to methods of treating cancer by administering an oncolytic virus and/or an anti-PD-1 antibody and/or an anti-CTLA4 antibody; however it is noted that the reference patents do not teach or suggest the administration of all three medicaments. These deficiencies are addressed by the cited references, as provided in the teachings specified in the 103 section.
The conflicting patents and the cited references are considered to be analogous to the present invention as they are in the same field of cancer/cancer therapeutics. It would have been obvious to one of ordinary skill in the art to develop methods of treating cancer by combining the administration of an anti-PD-1 antibody and an anti-CTLA4 antibody with the administration of an oncolytic virus, such as VSV strain Voyager V1 or VSV strain M51R, because there would be a reasonable expectation the resultant invention would be effective in treating various cancers by combining the administration of multiple anti-cancer medicaments.
Similarly, claims 1-24, 28-31, 36, and 41-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over the pertinent claims of the below listed U.S. Patent Nos. in view of the references cited in the rejection of the claims under 35 U.S.C. 103, specifically, Lala et al. (WO 2019/160755, international filing date: 02/08/2019), Sznol et al. (J Clin Oncol, volume 38, number 15, suppl., 2020), Silverman et al. (US PG PUB 20130071432, publication date 03/21/2013), and Papadopoulos et al. (US PAT 9,987,500, issue date: 06/05/2018).
Application No.
Brief Description of the Invention
Pertinent Claims
18/551,679
METHODS OF TREATING CANCER IN IMMUNOSUPPRESSED OR IMMUNOCOMPROMISED PATIENTS BY ADMINISTERING AN ANTI-PD-1 ANTIBODY
1 and 18-28
18/547,192
METHODS OF TREATING LUNG CANCER BY ADMINISTERING A PD-1 INHIBITOR
1, 2, and 11-17
18/839,107
COMBINATIONS OF CHECKPOINT INHIBITORS AND ONCOLYTIC VIRUS FOR TREATING CANCER
1-26 and 28-41
18/909,076
METHODS OF TREATING CANCER WITH A COMBINATION OF A PD1 INHIBITOR AND A TARGETED IMMUNOCYTOKINE
1, 6-8, and 11
The instant claims are rendered obvious by the combined teachings of the prior art above as discussed in the 103 section, the 103s being incorporated here.
It is noted that all of the conflicting applications are generally drawn to methods of treating cancer by administering an oncolytic virus and/or an anti-PD-1 antibody and/or an anti-CTLA4 antibody; however it is noted that the reference patents do not teach or suggest the administration of all three medicaments. These deficiencies are addressed by the cited references, as provided in the teachings specified in the 103 section.
The conflicting applications and the cited references are considered to be analogous to the present invention as they are in the same field of cancer/cancer therapeutics. It would have been obvious to one of ordinary skill in the art to develop methods of treating cancer by combining the administration of an anti-PD-1 antibody and an anti-CTLA4 antibody with the administration of an oncolytic virus, such as VSV strain Voyager V1 or VSV strain M51R, because there would be a reasonable expectation the resultant invention would be effective in treating various cancers by combining the administration of multiple anti-cancer medicaments.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642