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 .
Election/Restrictions
In accordance with the MPEP, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species and the claims drawn to the elected species are allowable, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
As indicated previously, the scope of the search and consideration includes the elected species and compound (8)
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. Since this scope remains unallowable, the scope of the search and consideration was not expanded further, and the claims have been amended such that they read only on the elected species.
Status of Claims
Currently, claims 18-22 are pending in the instant application. Claims 18-22 read on an elected invention and species and therefore remain under consideration in the instant application to the extent that they read on the elected embodiment.
Response to Remarks and Amendments
Applicant’s remarks and amendments filed May 13, 2025 have been entered and are considered herein. All rejections and objections not explicitly maintained herein are withdrawn. The rejections below constitute the full set of rejections being applied to the instant claims.
With respect the rejection under 35 USC 112(b) over claims 1 and 9-15, the rejection are withdrawn in view of the amendment to cancel the rejected claims.
With respect to the rejection of claims 1 and 9-19 (now 18-22) under 35 USC 103, Applicants traverse the rejection on several grounds, each of which has been considered but was not found persuasive to overcome the rejection. Applicants first contend that the ‘980 publication does not teach treating cancer with any A2A receptor inhibitors, and that Mittal teaches the treatment of only specific cancers with a combination of the A2A receptor inhibitor SCH58261 and an immune checkpoint blockade inhibitor. The antimetastatic effect of the A2A receptor inhibitor was found to depend upon CD73 expression on tumor cells. Applicant concludes that there is no evidence that the intstantly claimed cancers wiuld be treatable with an A2A receptor inhibitor. The examiner respectfully disagrees.
As an initial matter, the instantly claimed method utilizes open transitional language (“comprising”) such that nothing precludes the use of a combination of active agents for cancer treatment. Further, Applicants argue that the examiner’s conclusion is in error because the cancer effect of the A2A inhibitor in Mittal depends on the CD73 expression on tumor cells. This argument does not overcome the finding of obviousness at least for the reason that CD73-expressing cancer is actually a more narrow subset of cancers than the broadly claimed types of cancer, which include any cancer regardless of gene expression. The combination of references was found to provide a prima facie case of obviousness for utilizing a combination of a known A2A receptor inhibitor and a known immune checkpoint blockade inhibitor for the treatment of any cancer expressing CD73. Compound 32 of the ‘980 publication and compound SCH58261 of Mittal are both known A2A receptor inhibitors, and Mittal shows that this particular receptor activity is beneficial for treating cancers expressing CD73, which falls within the broader scope of the generic cancers recited in the instant claims.
Further, it is noted that the threshold for a prima facie case of obvious is simply a reasonable expectation that the invention would perform the claimed function. There is no requirement for an absolute guarantee of success, proven by a in vivo and in vitro experiments. There is no particular reason given for a person of ordinary skill in the art to doubt the findings and disclosure of Mittal, in particular that A2A receptor inhibitors can be used to treat cancer expressing CD70. In contrast to the cases cited by Applicant in the remarks, Mittal does provide data on cancer treatment with a combination of a known A2A receptor inhibitor and a known immune checkpoint blockade inhibitor for the treatment of any cancer expressing CD73, and the ‘980 publication provides data showing particular efficacy of the instantly claimed compound for A2A receptor inhibition. Further, as noted in the rejection, Mittal expressly teaches that there is a “strong rationale” for using known A2A receptor inhibitors for combination treatment with PD-1 blockers to treat metastatic disease (Abstract) and links the expectation of success to the receptor activity in the conclusion, noting the promising results observed upon combination of A2A receptor inhibition with anti-PD-1 “strongly advocate” for the use of substances having these mechanisms of action together for the treatment of metastatic disease (see “Conclusions”). Therefore, there exists an express suggestion in Mittal to use other A2A receptor inhibitors in the same combinatorial treatment and the combined data from the ‘980 publication and Mittal would have provided at least the requisite reasonable expectation of success. Accordingly, the rejection is maintained herein.
With respect to the rejection of claims 1 and 9-19 (now claims 18-22) for double patenting over the claims of the ‘177 patent, Applicants contend that the rejection should be withdrawn because the examiner’s reliance on Sun Pharmaceuticals is in error, noting that the ‘177 patent does not disclose a utility for treating cancer. The examiner respectfully disagrees that the rejection is in error. As noted in the rejection, the ‘177 patent discloses a utility as A2A receptor inhibitors, which provides the requisite motivation to combine the ‘177 patent claims with Mittal, which relates specifically to combinations of A2A receptor inhibitors with anti-PD-1 for the treatment of cancer.
Applicant goes on to argue that even if there were motivation to combine the claims with Mittal, there would have been no reasonable expectation of success in using the claimed A2A receptor inhibitor for treating cancer. Applicant refers to the arguments made with respect to the 103 rejection. The examiner incorporates the rebuttal of Applicant’s arguments from paragraphs 9-10 above herein. Accordingly, the rejection is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim 18-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012/038980 (“the ‘980 publication”) in view of Mittal et al.
Applicant’s invention is directed to a method of treating cancer comprising administering a compound of Formula I, in particular the elected species or compound (8) to which the scope of the search has been expanded.
A) Determining the scope and contents of the prior art:
Regarding claim 18, the ‘980 publication teaches compounds of the formula
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as “potent antagonists of the A2A adenosine receptor (see p. 5, lines 1-10). Notably, among the many disclosed compounds which anticipate instant formula (I), the ‘980 publication teaches instant compound (32) as A31 at page 55. Further, the binding activity described in the table printed at page 98 shows A2A cell based functional Ki data in units of molarity, which is an indication that a solution of the anticipatory compounds, including the elected species (see “particular embodiments” of the disclosure, and example A31) was necessarily prepared in order to conduct the prior art assay (see “Competition Assays” section above the table for a description of the composition preparation). Use of the compounds in the treatment of various diseases related to the adenosine A2A receptor activity is disclosed throughout the reference, for example see Abstract. In addition, the reference provides in vitro A2A cell based data for both A7 and A31, describing them both as having binding activity in the most efficacious range reported in the assay (see p. 98, Table).
B) Ascertaining the differences between the prior art and the claims at issue.
The primary reference differs in that the ‘980 publication fails to explicitly disclose where the A2A receptor inhibitors disclosed therein are used to treat cancer.
C) Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at ___, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Based on the teachings of the MPEP and KSR above, by employing the rationale in (B) above, it would have been obvious for one of ordinary skill in the art to substitute any known adenosine receptor antagonist for another active agent known to have the same function/utility. To this end, the ‘980 publication teaches adenosine receptor modulating compounds for treatment of certain diseases associated with the A2A receptor. Further, Mittal et al. describes adenosine receptor targeting, in particular the A2A receptor, as “an attractive new approach to cancer treatment” (see Abstract). Mittal further describes that many adenosine A2A receptor inhibitors have demonstrated safe clinical profiles for the treatment of other diseases (Parkinsons, for example), concluding that there is a “strong rationale” for using known A2A receptor inhibitors for combination treatment with PD-1 blockers to treat metastatic disease (Abstract). The A2A receptor inhibitors in the Mittal study were tested on mouse models for melanoma and triple negative breast cancer (See “Cells” under “Materials and Methods” section; 1st paragraph under “Results and Discussion” section). Mittal also teaches that the A2A receptor inhibitor SCH58261 was demonstrated as having a protective effect on mice with lung metastases (id.) . Finally, it is disclosed the promising results observed upon combination of A2A receptor inhibition with anti-PD-1 “strongly advocate” for the use of substances having these mechanisms of action together for the treatment of metastatic disease (see “Conclusions”). The motivation to arrive at the claimed method of treating cancer would have been to provide a cancer treating combination of a known adenosine receptor antagonist and PD-L1 antibody as described in Mittal et al., while substituted another known adenosine receptor antagonist with a reasonable expectation of success due to the demonstrated in vitro receptor activity already descry the compounds in the ‘980.
Therefore, it would have been prima facie obvious at the time of filing for one of ordinary skill in the art to use the combination of active ingredients suggested by the references, which requires only carrying out the explicit suggestion of Mittal for developing new combinatorial therapy for cancer treatment with A2A receptor inhibitors. Use of compounds already described in the art as having the same mechanism of action and being therapeutically useful would have provided the requisite reasonable expectation of success.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 18-22 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-14 of US Patent 9,006,177 in view of Mittal et al.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined 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).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the instantly claimed compositions are anticipated by those in the patented claims. In particular, the conflicting claims recite compounds of the formula
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as well as pharmaceutical compositions/combinations thereof (claims 7 and 10-14). By way of particular examples, many anticipatory compounds are explicitly claimed, including the elected species (see patented claim 6).
It is noted that the instant claims are drawn to methods of treating cancer, while the conflicting claims are directed to a different statutory class of invention (compositions or compounds rather than methods of use). To this end, the Federal Circuit, in Sun v. Lilly, recounts its own decisions in Geneva and Pfizer,
In both cases, we found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent.
Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 at 1800 (Fed. Cir. 2010).
In reaffirming its holding in Geneva and Pfizer, the Court finds that a "claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use.” (Id. at 1801, quoting Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. The Court reasserts this notion by stating,
[i]t would shock one's sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. Pfizer, 518 F.3d at 1363 n.8 (emphases added); Geneva, 349 F.3d at 1386 (quoting In re Byck, 48 F.2d 665, 666 [9 USPQ 205] (CCPA 1931)).
Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 at 1802 (Fed. Cir. 2010).
Section 804 IIb of the M.P.E.P. states
...those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because only "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
In the instant case, the specification and title of the conflicting patent identifies the compounds and compositions as having efficacy as adenosine receptor antagonistic activity, which are useful for treating conditions such as Parkinson’s Disease and others (see Abstract). The utility described for the ‘177 compounds does not cover the cancer treatment required by the instant claims. However, the conflicting patent discloses a utility for the compounds and compositions claimed therein as inhibitors of the A2A receptor, where this utility combined with the teachings of Mittal et al. would have rendered the instant claims obvious over those of the ‘177 patent. Mittal et al. describes adenosine receptor targeting, in particular the A2A receptor, as “an attractive new approach to cancer treatment” (see Abstract). Mittal further describes that many adenosine A2A receptor inhibitors have demonstrated safe clinical profiles for the treatment of other diseases (Parkinsons, for example), concluding that there is a “strong rationale” for using known A2A receptor inhibitors for combination treatment with PD-1 blockers to treat metastatic disease (Abstract). The A2A receptor inhibitors in the Mittal study were tested on mouse models for melanoma and triple negative breast cancer (See “Cells” under “Materials and Methods” section; 1st paragraph under “Results and Discussion” section). Mittal also teaches that the A2A receptor inhibitor SCH58261 was demonstrated as having a protective effect on mice with lung metastases (id.) . Finally, it is disclosed the promising results observed upon combination of A2A receptor inhibition with anti-PD-1 “strongly advocate” for the use of substances having these mechanisms of action together for the treatment of metastatic disease (see “Conclusions”). The motivation to arrive at the claimed method of treating cancer would have been to provide a cancer treating combination of a known adenosine receptor antagonist and PD-L1 antibody as described in Mittal et al., while substituting another known adenosine receptor antagonist with a reasonable expectation of success due to the described utility as A2A receptor inhibitors in the ‘177 patent.
Therefore, it would have been prima facie obvious at the time of filing for one of ordinary skill in the art to use the combination of active ingredients suggested by the ‘177 claims, which requires only carrying out the explicit suggestion of Mittal for developing new combinatorial therapy for cancer treatment with A2A receptor inhibitors. Use of compounds already described in the art as having the same mechanism of action and being therapeutically useful would have provided the requisite reasonable expectation of success.
Since the patented claims render obvious all the required features of the instant claims, a double patenting rejection is appropriate.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alicia L. Otton whose telephone number is (571)270-7683. The examiner can normally be reached on Monday - Thursday, 8:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Fereydoun Sajjadi can be reached on 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALICIA L OTTON/Primary Examiner, Art Unit 1699
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