DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a continuation of U.S. Application No. 18/165,262 filed on February 6, 2023, now abandoned, which is a continuation of U.S. Application No. 16/358,311 filed on March 19, 2019, now abandoned, which is a continuation in part of U.S. Application No. 16/139,745 filed on September 24, 2018, now U.S. Patent No. 11,304,952, which claims priority to U.S. Provisional Application No. 62/562,952 filed on September 25, 2017.
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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 16/139,745, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. There is no disclosure in the prior filed application for CCR2 antagonists represented by the compounds of claim 1. As such claim 1 and all claims wherein the CCR2 antagonist is a compound as claimed in claim 1 are given the effective filing date of March 19, 2019 which is the actual filing date of U.S. Application No. 16/358,311.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 8, 2026 has been entered.
Response to Amendment
By Applicant’s amendment filed January 8, 2026 claim 1 has been amended. Claims 10, 11, 16, 17, 33 and 36 are withdrawn. Claims 2-9, 14, 18, 19, 21, 25, 27-32, 34, 35 and 37-40 were previously canceled.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are currently presented for examination.
Response to Arguments
The terminal disclaimer filed on January 8, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on U.S. Application No. 17/694,829 has been reviewed and is accepted. The terminal disclaimer has been recorded.
The terminal disclaimer filed on January 8, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,304,952 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Accordingly, the previous double patenting rejections over U.S. Application No. 17/694,829 and U.S. Patent No. 11,304,952 are hereby withdrawn.
The remaining double patenting rejections are hereby maintained and reproduced below since Applicant’s arguments have been fully considered but are found not persuasive.
With respect to the remaining nonstatutory double patenting rejections, Applicant argues that the addition of the limitation "the number of long term survivors is increased by the combination of the CCR2 chemokine receptor antagonist and PD-1 and/or PD-L1 inhibitor" is neither taught nor suggested by any of the remaining combinations of references.
This argument is found not persuasive since each of the patents cited in view of the secondary references cited render obvious the claimed method of treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab. Therefore the results of the method as claimed which is the number of long term survivors is increased by the combination of the CCR2 chemokine receptor antagonist and PD-1 and/or PD-L1 inhibitor is also rendered obvious since administration of the same compounds for the same purpose will necessarily have the same effects as claimed. Thus since the patents in view of the secondary references render obvious treating the same patient population having colorectal cancer, the same effect of increasing the number of long term survivors will necessarily occur by following the teachings and suggestions of the prior art. Thus Applicant’s arguments are found not persuasive and the previous remaining double patenting rejections are hereby maintained and reproduced below.
Applicant's arguments filed January 8, 2026 with respect to the rejection under 35 USC 103 over Bekker in view of Brake have been fully considered but they are not persuasive.
Applicant argues that claim 1 is amended to specify that the currently claimed method increases the number of long-term survivors and neither of the cited references discloses, teaches, or suggests that the currently claimed method of treatment would increase the number of long-term survivors in colorectal cancer.
This argument is found not persuasive because Bekker et al. in view of Brake et al. render obvious the claimed method of treating colorectal cancer comprising administering a therapeutically effective amount of the CCR2 chemokine receptor antagonist
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in combination with the PD-1 inhibitor pembrolizumab. Therefore the results of the method as claimed which is the number of long term survivors is increased by the combination of the CCR2 chemokine receptor antagonist and PD-1 and/or PD-L1 inhibitor is also rendered obvious since administration of the same compounds for the same purpose will necessarily have the same effects as claimed. Thus since Bekker et al. in view of Brake et al. render obvious treating the same patient population having colorectal cancer comprising the same combination of compounds as claimed, the same effect of increasing the number of long term survivors will necessarily occur by following the teachings and suggestions of the prior art. In addition, it is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013 (CCPA 1972); In re Dillon, 919 F.2d 688 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). The mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Prindle, 297 F.2d 251, 254 (CCPA 1962). Here, the latent property identified by Applicant is that the method will increase the number of long-term survivors. This limitation does not patentably distinguish the claims over the prior art cited since this result will necessarily occur by following the teachings and suggestions of the prior art and administering the claimed compounds for the treatment of colorectal cancer.
Applicant further argues the following: neither Brake nor Bekker teach that a small molecule CCR2 receptor antagonist, such as the ones claimed, can treat colorectal cancer; Bekker fails to provide a teaching, suggestion, or motivation to select a PD-1 and/or PD-L1 inhibitor, much less an inhibitor selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab, durvalumab, atezolizumab, avelumab, ipilimumab, and tremelimumab; and the cited references fail to provide one of ordinary skill in the art a reasonable expectation of successfully treating colorectal cancer with the currently claimed combination.
Applicant further argues that Bekker is directed to the use of compounds of Formula I for the treatment of only pancreatic cancer and no discussion is provided in Bekker for the treatment of colorectal cancer. Applicant further argues that Brake is directed to the use of an anti-PD1 antibody and an anti-CCR2 antibody in the treatment of non-small cell lung cancer with no teaching or suggestion for replacing an antibody with a small molecule. Applicant further argues that the treatment of any cancer other than non-small cell lung cancer is described only in another long list of potential treatments recited over four separate paragraphs, with no direction to select any one particular cancer.
Applicant further argues that Bekker provides the use of additional therapeutics as a huge list of alternatives, with no direction for picking a PD-1 inhibitor or a PD-L1 inhibitor.
Applicant argues that without applicant's discovery that the currently claimed combination results in a successful treatment of colorectal cancer, one of ordinary skill in the art reviewing Brake and Bekker would not reasonably expect the claimed combination would have that therapeutic outcome because neither of the references contain any data demonstrating that CCR2 inhibitors could treat colorectal cancer alone, much less in combination with a PD-1 and/or PD-L1 inhibitor. Applicant argues that even if the Office Action construes Bekker as suggesting the use of PD-1 and/or PD-L1 inhibitors, Bekker does not contain any data demonstrating a positive effect of the use of such inhibitors and Brake does not cure this deficiency. Applicant further argues that the rejection fails to articulate why one of ordinary skill in the art would reasonably expect the claimed combination to successfully treat colorectal cancer in light of the fact that none of the references contain any data for treating colorectal cancer with any of the claimed compounds or antibodies, much less the currently claimed combination of a CCR2 small molecule inhibitor and a PD-1 and/or PD-L1 antibody. Thus, Applicant argues that a person of ordinary skill would not have a reasonable expectation of success in treating colorectal cancer using the currently claimed combination.
These arguments are found not persuasive since both Bekker and Brake specifically teach combining the inhibition of both PD-1/PD-L1 and CCR2 for the treatment of cancer.
Bekker specifically teaches the same CCR2 inhibitor compounds as claimed in the instant claims useful in the treatment of cancer including adenocarcinoma and furthermore teaches that these compounds can be combined with other active agents such as PD-1/PD-L1 inhibitors [0015]-[0019].
Although Bekker does not specifically exemplify combining the CCR2 antagonist compounds with PD-1/PD-L1 inhibitors and treating colorectal cancer as claimed, these deficiencies are cured by the teachings of Brake.
The claims of Brake specifically claim a method for treating a cancer in an individual comprising administering to the individual a combination therapy which comprises an antagonist of a Programmed Death 1 protein (PD-1) and an anti-CCR2 antibody, wherein the PD-1 antagonist is a monoclonal antibody, or an antigen binding fragment thereof, which specifically binds to human PD-1 and blocks the binding of human PD-L1 and/or PD-L2 to human PD-1; or a monoclonal antibody, or an antigen binding fragment thereof, which specifically binds to human PD-L1 and blocks the binding of human PD-L1 to human PD-1 such as nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab and the anti-CCR2 antibody is plozalizumab (see claims 1-7). Thus the teachings of Brake establish an art recognized combination of inhibition of CCR2 and PD-1 for the treatment of cancer.
Brake further specifically teaches in some embodiments, the cancer treated is gastrointestinal cancer, which includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake specifically teaches that the combination of inhibition of CCR2 and PD-L1/PD-1 is useful for the treatment of gastrointestinal cancer including pancreatic cancer and colorectal (large intestine and rectum) cancer. Moreover, the teachings of Brake specifically focus on the inhibition of both CCR2 and PD-L1/PD-1 for the treatment of cancer. Brake specifically discusses the advantages of combining the inhibition of both CCR2 and PD-L1/PD-1 for the treatment of cancer including significantly higher anti-tumor efficacy compared to either agent alone and a superior clinical benefit with a better safety profile ([0002] [0025]).
Thus, based on the combination of the teachings of Bekker and Brake, it would have been obvious to a person of ordinary skill in the art to combine the compounds of Bekker that inhibit CCR2 with a PD-1 antagonist such as pembrolizumab since Brake specifically teaches the advantages of inhibition of both CCR2 and PD-1/PD-L1 in the treatment of cancer including gastrointestinal cancers such as pancreatic and colorectal cancer, such as a superior clinical benefit with a better safety profile,.
Moreover, even though Brake discusses the treatment of cancers other than colorectal cancer, it has been well established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the admitted knowledge in the art, to a person of ordinary skill in the art. In re Boe, 355 F.2d 961,148 USPQ 507, 510 (CCPA 1966); In re Lambedi, 545 F.2d 747, 750, 192 USPQ 279,280 (CCPA 1976): In re FracalossL 681 F.2d 792,794, 215 USPQ 569, 570 (CCPA 1982)4 In re Kaslow, 707 F.2d 1366, 13:4,217 USPQ 1089, 1095 (Fed. Cir. 1983). Furthermore, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have “relatively acceptable dimensional stability” and “some degree of flexibility,” but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since “Gurley asserted no discovery beyond what was known in the art.” 27 F.3d at 554, 31 USPQ2d at 1132.). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Moreover, a prima facie case of obviousness can still be established since picking one of a finite number of known solutions to a known problem is prima facie obvious. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Furthermore, even though Bekker discloses small molecule compounds that are CCR2 antagonists that inhibit CCR2 activity and Brake discloses an anti-CCR2 antibody which inhibits CCR2 activity, the end result is the same which is the inhibition of CCR2 activity for the treatment of cancer. Therefore, there would have been a reasonable expectation of similar success by substituting an anti-CCR2 antibody which inhibits CCR2 activity for a small molecule compound that is a CCR2 antagonist which inhibits CCR2 activity. Applicant has not provided any evidence that there would have been any difference in treatment by administering a small molecule compound over an anti-CCR2 antibody. Thus, there would have been a reasonable expectation of similar success in view of the teachings of Brake for treating colorectal cancer comprising the CCR2 antagonist compounds of Bekker combined with a PD-1/PD-L1 inhibitor.
With respect to Applicant’s argument that the references do not provide any data demonstrating that CCR2 inhibitors could treat colorectal cancer alone, much less in combination with a PD-1 and/or PD-L1 inhibitor, obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O ’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988). Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014). Proof sufficient “to obtain approval” for a drug by a regulatory agency, such as by a randomized, placebo-controlled, double-blinded design is not necessary to establish obviousness. Hoffmann—La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014) (“[c]onclusive proof of efficacy is not necessary to show obviousness.”). “Scientific confirmation of what was already believed to be true may be a valuable contribution, but it does not give rise to a patentable invention.” PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1363-64 (Fed. Cir. 2007).
In the instant case, for the reasons detailed above, there is a reasonable expectation that the claimed compound would be useful in the treatment of colon cancer since Bekker et al. teaches that the compounds claimed in the instant claims can be combined with an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab [0015] for the treatment of cancer and Brake specifically teaches the combination of inhibition of PD-1/L1 and CCR2 for the treatment of gastrointestinal cancers such as colorectal cancer.
Thus for reasons of record, and for the reasons detailed above, the previous rejection under 35 USC 103 is hereby maintained and reproduced below because Applicant’s newly added limitation of requiring the number of long term survivors to increase does not change the scope of the claims since said effect will necessarily occur by following the teachings and suggestions of the prior art as detailed in the rejection of record. This action is FINAL.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,251,888 in view of Brake et al. WO 2017/165125 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘888 are substantially overlapping in scope and mutually obvious.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application claim a method for treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab.
Claims 1-8 of ‘888 claim a method for treating pancreatic cancer comprising administering a compound of formula I which are the same compounds as claimed in the instant claims, and further comprising administering an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor.
‘888 does not claim treating colon cancer.
However, Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2. Thus Brake et al. teaches that inhibition of both PD-1 or PD-L1 and CCR2 is useful in the treatment of pancreatic and colorectal cancer.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the claims of ‘888 which specifically claim a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of the compounds as claimed in the instant claims and further administering one or more additional therapeutic compounds such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, and large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist as claimed in the instant claims and ‘888 with a PD-1 inhibitor such as pembrolizumab for the treatment of colorectal cancer since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile for gastrointestinal cancers including pancreatic cancer, and large intestine/rectum (colorectal) cancer. Thus, in view of the teachings of Brake et al. one would apply the method of ‘888 for the treatment colorectal cancer to arrive at the instant invention.
Thus the cited claims of the instant application and the cited claims of ‘888 are mutually obvious and not patentably distinct.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,398,685 in view of Brake et al. WO 2017/165125 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘685 are substantially overlapping in scope and mutually obvious.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application claim a method for treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab.
Claims 1-18 of ‘685 claim a method for limiting over-expression of oncogenes, activating tumor suppressor genes, or regulating signaling proteins to treat patients diagnosed with pancreatic cancer comprising administering a compound of formula I which are the same compounds as claimed in the instant claims, and further comprising administering an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab.
‘685 does not claim treating colon cancer.
However, Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2. Thus Brake et al. teaches that inhibition of both PD-1 or PD-L1 and CCR2 is useful in the treatment of pancreatic and colorectal cancer.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the claims of ‘685 which specifically claim a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of the compounds as claimed in the instant claims and further administering one or more additional therapeutic compounds such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, and large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist as claimed in the instant claims and ‘685 with a PD-1 inhibitor such as pembrolizumab for the treatment of colorectal cancer since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile for gastrointestinal cancers including pancreatic cancer, and large intestine/rectum (colorectal) cancer. Thus, in view of the teachings of Brake et al. one would apply the method of ‘685 for the treatment colorectal cancer to arrive at the instant invention.
Thus the cited claims of the instant application and the cited claims of ‘685 are mutually obvious and not patentably distinct.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,583,131 in view of Brake et al. WO 2017/165125 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘131 are substantially overlapping in scope and mutually obvious.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application claim a method for treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab.
Claims 1-19 of ‘131 claim a method for controlling an adenocarcinoma such as a pancreatic adenocarcinoma comprising administering a compound of formula I which are the same compounds as claimed in the instant claims, and further comprising administering an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab.
‘131 does not claim treating colon cancer.
However, Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2. Thus Brake et al. teaches that inhibition of both PD-1 or PD-L1 and CCR2 is useful in the treatment of pancreatic and colorectal cancer.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the claims of ‘131 which specifically claim a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of the compounds as claimed in the instant claims and further administering one or more additional therapeutic compounds such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, and large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist as claimed in the instant claims and ‘131 with a PD-1 inhibitor such as pembrolizumab for the treatment of colorectal cancer since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile for gastrointestinal cancers including pancreatic cancer, and large intestine/rectum (colorectal) cancer. Thus, in view of the teachings of Brake et al. one would apply the method of ‘131 for the treatment colorectal cancer to arrive at the instant invention.
Thus the cited claims of the instant application and the cited claims of ‘131 are mutually obvious and not patentably distinct.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 U.S. Patent No. 11,116,756 B2 in view of Brake et al. WO 2017/165125 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘756 are substantially overlapping in scope and mutually obvious.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application claim a method for treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab.
Claims 1-15 of ‘756 claim a method for treating pancreatic cancer comprising administering a compound of formula I which are the same compounds as claimed in the instant claims, and administering an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab.
‘756 does not claim treating colon cancer.
However, Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2. Thus Brake et al. teaches that inhibition of both PD-1 or PD-L1 and CCR2 is useful in the treatment of pancreatic and colorectal cancer.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the claims of ‘756 which specifically claim a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of the compounds as claimed in the instant claims and further administering one or more additional therapeutic compounds such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, and large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist as claimed in the instant claims and ‘756 with a PD-1 inhibitor such as pembrolizumab for the treatment of colorectal cancer since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile for gastrointestinal cancers including pancreatic cancer, and large intestine/rectum (colorectal) cancer. Thus, in view of the teachings of Brake et al. one would apply the method of ‘756 for the treatment colorectal cancer to arrive at the instant invention.
Thus the cited claims of the instant application and the cited claims of ‘756 are mutually obvious and not patentably distinct.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 U.S. Patent No. 11,890,276 B2 in view of Brake et al. WO 2017/165125 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the cited claims of the instant application and the cited claims of ‘276 are substantially overlapping in scope and mutually obvious.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application claim a method for treating cancer such as colorectal cancer comprising administering a therapeutically effective amount of a CCR2 chemokine receptor antagonist such as
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in combination with a PD-1 inhibitor and/or PD-L1 inhibitor such as pembrolizumab.
Claims 1-23 of ‘276 claim a method for controlling an adenocarcinoma such as pancreatic adenocarcinoma comprising administering a compound of formula I which are the same compounds as claimed in claims 9 and 12 of the instant application, and administering an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab.
‘276 does not claim treating colon cancer.
However, Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2. Thus Brake et al. teaches that inhibition of both PD-1 or PD-L1 and CCR2 is useful in the treatment of pancreatic and colorectal cancer.
Accordingly, prior to the effective filing date of the instant claims, it would have been obvious to a person of ordinary skill in the art to combine the claims of ‘276 which specifically claim a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of the compounds as claimed in the instant claims and further administering one or more additional therapeutic compounds such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, and large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist as claimed in the instant claims and ‘276 with a PD-1 inhibitor such as pembrolizumab for the treatment of colorectal cancer since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile for gastrointestinal cancers including pancreatic cancer, and large intestine/rectum (colorectal) cancer. Thus, in view of the teachings of Brake et al. one would apply the method of ‘276 for the treatment colorectal cancer to arrive at the instant invention.
Thus the cited claims of the instant application and the cited claims of ‘276 are mutually obvious and not patentably distinct.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Bekker et al. U.S. Publication No. 2017/0354657 A1 in view of Brake et al. WO 2017/165125 A1.
Claims 1, 12, 13, 15, 20, 22-24 and 26 of the instant application as they read on the elected species claim a method for treating colorectal cancer comprising administering a therapeutically effective amount of the CCR2 chemokine receptor antagonist
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in combination with the PD-1 inhibitor pembrolizumab.
Bekker et al. discloses compounds of Formula I for the treatment of pancreatic cancer [0015]. The compounds of Formula I modulate CCR2 chemokine ligand activity [0013]. Bekker et al. specifically teach compound Ib as a compound of Formula I which is the same as Applicant’s elected species of a CCR2 chemokine receptor antagonist [0015]. Bekker et al. teaches that the compound can be combined with an additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab [0015]. Bekker et al. specifically teaches a method of treating pancreatic cancer in a patient comprising administering an effective amount of a compound of Formula Ib:
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and further administering one or more additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor including pembrolizumab [0072].
Bekker et al. does not teach treating colorectal cancer. Bekker et al. does not specifically exemplify combining the CCR2 antagonist with the PD-1 inhibitor pembrolizumab.
Brake et al. teaches methods for the treatment of cancers by administering anti-PD-1 antagonists in combination with anti-CCR2 antibodies (abstract). Brake et al. teaches that the concurrent administration of a PD-1 antagonist and an anti-CCR2 antibody results in significantly higher anti-tumor efficacy compared to either agent alone [0002]. Brake et al. further teaches that the combination can provide superior clinical benefit with a better safety profile [0025]. Brake et al. teaches that plozalizumab is a potent specific antagonist of CCR2 [0004]. Brake et al. specifically teaches a method for treating cancer comprising administration of a combination of a PD-1 antagonist and an anti-CCR2 antibody which is plozalizumab [0005]-[0010]. Brake et al. further teaches that the PD-1 antagonist inhibits binding of PD-L1 and/or PD-L2 to PD-1 and in some embodiments the PD-1 antagonist is a monoclonal antibody selected from the group consisting of nivolumab and pembrolizumab ([0009] and [0064]-[0066]). Brake et al. further teaches that the cancer is a solid tumor [0011]. Brake et al. teaches treatable cancers include breast cancer, skin cancer, bone cancer, prostate cancer, lung cancer, and colon cancer [0042]-[0046]. Brake et al. teaches in a specific embodiment, the cancer treated is gastrointestinal cancer wherein the gastrointestinal cancer includes cancer of the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus [0046]. Thus Brake et al. teaches the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer comprising the administration of inhibitors of PD-1 and CCR2.
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Bekker et al. which specifically teaches a method of treating the gastrointestinal cancer, pancreatic cancer in a patient comprising administering an effective amount of a compound of Formula Ib:
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which is a CCR2 chemokine receptor antagonist and further administering one or more additional therapeutic compound such as a PD-1 inhibitor or a PD-L1 inhibitor such as pembrolizumab, with the teachings of Brake et al. which teaches a method of treating cancers including the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer, comprising the specific combination of a CCR2 chemokine receptor antagonist and a PD-1 inhibitor, specifically nivolumab or pembrolizumab. Thus in view of the teachings of Brake et al., an ordinary skilled artisan would have been especially motivated to combine the CCR2 antagonist of Bekker et al. with a PD-1 inhibitor such as pembrolizumab since Brake et al. specifically teaches that the combination of a PD-1 antagonist and a CCR-2 antagonist results in significantly higher anti-tumor efficacy compared to each agent alone leading to superior clinical benefit with a better safety profile. Moreover, an ordinary skilled artisan would have been motivated to treat other gastrointestinal cancers in addition to pancreatic cancer, including large intestine/rectum (colorectal) cancer with the combination based on the teachings of Brake et al. which specifically teaches that the combination of a CCR2 antagonist and a PD-1 antagonist can be used to treat several types of cancers including the treatment of gastrointestinal cancer including pancreatic, large intestine/rectum (colorectal) cancer.
Claims 20 and 22-24 of the instant application are rendered obvious since Brake et al. teaches that each therapeutic agent in the combination therapy may be administered simultaneously (in the same medicament), concurrently (in separate medicaments administered one right after the other in any order), or sequentially in any order [00100]. Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 10, 11, 16, 17, 33 and 36 are withdrawn. Claims 2-9, 14, 18, 19, 21, 25, 27-32, 34, 35 and 37-40 are canceled. Claims 1, 12, 13, 15, 20, 22-24 and 26 are rejected. No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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