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 .
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.
Election/Restrictions
Examiner have maintained 103 rejection on file.
Claims 2,12, 16-22, 24 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 July 15th 2025.
Claims 1, 7-11, 14-15, 25-26 and 28 are examined on merits in this office action.
Current Status of 17/786,037
This Office Action is in response to the amended claims of 12/01/2025.
Claims 1, 15 and 17 are currently amended; claims 7-11 and 14 are original; claims 18-22 and 24 were previously amended; and claim 25-28 are new.
Claims 2,12, 16-22, 24 are withdrawn
Claims 1, 7-11, 14-15, 25-26 and 28 are examined on merits in this office action.
Priority
The effective filing date is 01/07/2020 because claims find support in the provisional application no. 62/957,806.
Response to Arguments
Examiner acknowledges the receipt of applicant’s claim amendment and remarks of 12/01/2025. Examiner have reviewed these remarks and amendments.
Applicant filed declaration / affidavit 12/01/2025
Regarding 35 U.S.C 103 rejection,
applicants amended claim 1 to include “and (iii) a chemotherapeutic drug….”.
Applicant submitted declaration or affidavit where the applicants have conducted experiments to demonstrate the alleged surprising and unexpected result of combination of compound of formula I, with immunotherapy and chemotherapy drugs in tumors that are intrinsically resistant to immunotherapy (page 4-5 of affidavit)
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Applicant argues Claims are drawn to method of treating cancer in a subject in need thereof comprising administering combination of compound of formula I, immunotherapeutic agent and chemotherapeutic drug are not obvious because there is long-felt need for treating resistant “cold” tumor
Examiner Response:
Examiner disagrees, as synergistic effect for treating colon cancer with the combination of compound
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where Y =NH; R1=
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(aryl) (Wu et.al. compound XC608, column 24 lines 1-150)(applicant’s elected species) with gemcitabine(applicant elected species of chemotherapy agent) (Wu et.al. column 29, lines 40-67) is disclosed by Wu et.al. Alsaab et.al further teaches an immunotherapeutic agent acts synergistically in combination with another chemotherapy agent (pg 12, col 2, para 2).
Synergistic effect is highly unpredictable (Zhang C, Yan G. Synergistic drug combinations prediction by integrating pharmacological data. Synth Syst Biotechnol. 2019 Feb). Synergy might be acceptable for a single combination, or combinations presented in the affidavit but not for the breadth of 3 components where 2 are purely functionally defined and the defined compounds is highly variable. Claims 1 and 17 does not recites one species of immunotherapeutic agents with one species of chemotherapy drugs in combination with compound of formula I. Therefore, the scope of claim 1 and 17 is too broad to be surprising and unexpected and are not addressed by the affidavit for treating all cancers with all combinations of chemotherapy drugs, immunotherapeutic agents and compounds of formula 1.
Applicant argues the claimed subject matter solved a problem that was long standing in the art. However, there is no showing that others of ordinary skill in the art were working on the problem and if so, for how long. In addition, there is no evidence that if persons skilled in the art who were presumably working on the problem knew of the teachings of the above cited references, they would still be unable to solve the problem. See MPEP § 716.04.
Applicant did not provide objective evidence of long-felt need (MPEP 716.04): namely, Applicants did not provide objective evidence that recognized problem exists for method of treating cancers as broadly stated in the claims. Although the claimed invention achieved the desirable result, applicant did not provide evidence of prior unsuccessful attempts for method of treating cancers with the composition stated in the claims.
Therefore, 103 rejections are maintained for the reason stated above in examiner response.
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).
Claim Rejections - 35 USC § 103(maintained with modification)
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.
Claim(s) 1, 7-11, 14-15, 25-26 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over
Wu et. al. (US 9,487,539)
In view of
Alsaab et. al. (23 August 2017doi: 10.3389/fphar.2017.00561)
In further view of
Yan et.al. (MABS, 2019, VOL. 11, NO. 4, 681–690).
In further view of
Anisel et.al. “PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS” 7th edition, 1999.
1. Determining the scope and contents of the prior art.
Claims are drawn to method of treating cancer in a subject in need thereof comprising administering combination of compound of formula I, immunotherapeutic agent and chemotherapeutic drug. Wu teaches a method for treating colon cancer (applicant elected species of cancer, therefore is interpreted as cancer that does not respond to immunotherapy as a monotherapy (claims 26)) with the compound
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(aryl), 2-(3-fluorophenyl)-4-(3-piperidineamino)-thieno[2,3-d]pyridazine-7-carboxylic acid amide, (compound XC608, column 24 lines 1-150) (applicant’s elected species) enhances the effect of gemcitabine(applicant elected species of chemotherapy agent) (column 29, lines 40-67), partially teaching claim 1, 7-11, 14-15, 26 and 28.
Alsaab teaches a treatment for cancer based on immunotherapeutic agent (pg 2, col 1, para 2,) and Alsaab further teaches an immunotherapeutic agent acts synergistically in combination with another chemotherapy agent (pg 12, col 2, para 2) partially teaching claims 1 and 7-8. Alsaab further teaches wherein the immunotherapeutic agent or the therapeutic agent targeting a cancer-promoting molecule is an inhibitor of PD-1 (abstract) partially teaching claim 9 and 28. Alsaab further teaches wherein the antibody targeting PD-1 is consisting of Nivolumab (pg 6, col 1, para 2) teaching claims 9-10. PD-1 inhibitors treated in combination with antineoplastic agents (chemotherapy agent), to achieve a long lasting synergistic anti-cancer effect (pg 13, col 1, para 2)
Yan et. al teaches toripalimab (applicant’s elected antibody for targeting pd-1) antibody targeting Pd-1 in treating tumors (abstract) partially teaching claims 10-11.
Anisel et.al. teaches dosages of pharmaceuticals and frequency of the dosage are routinely optimized based on body weight and body surface area (Anisel et.al. page 50)
2. Ascertaining the differences between the prior art and the claims at issue.
Wu et. al does not teach the compounds formula I in combination with an immunotherapeutic agent or a therapeutic agent targeting a cancer-promoting molecule.
Alsaab does not teach use of compound of formula I in combination with an immunotherapeutic agent or a therapeutic agent targeting a cancer-promoting molecule.
Yan et. al. does not teach use of compounds of formula I in combination with an immunotherapeutic agent or a therapeutic agent targeting a cancer-promoting molecule.
3. Resolving the level of ordinary skill in the pertinent art.
The level of ordinary skill is an artisan who have sufficient background in cancer research and is developing effective treatment for cancers with combination of drugs.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
A person skilled in the art would be motivated to combine compounds of formula I,
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, with gemcitabine (chemotherapy agent) to treat colon cancer (Wu et.al, column 29, lines 40-67); with antibody that targets PD-1(a cancer promoting target) (Alsaab pg 6, col 1, para 2 and pg 13, col 1, para 2) to increase long lasting synergistic effect of gemcitabine for treating colon cancer. Moreover compound
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increases the effectiveness of gemcitabine in treating colon cancer (Wu et. al. column 29, lines 40-67). Therefore, it would be expected that combining compound
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, gemcitabine, and PD-1 antibody for treating colon cancer would be more effective in treating colon cancer with PD-1 antibody since the PD-1 antibody is known to target cancer/tumors (see Alsaab citation, above). Thus, teaching all the elements of claims 1, 7-11, 14-15, 26 and 28.
Furthermore, a person skilled in the art would be motivated to use toripalimab, an antibody, targeting cancer promoting molecule, PD-1 (Yan et. al, abstract) with the combined teaching of Wu et. al. and Alsaab et. al, as stated above, by replace the PD-1 antibody Nivolumab (Alsaab pg 6, col 1, para 2) with another PD-1 antibody toripalimab. Since toripalimab is expected to be same or better at treating colon cancer when combined with compound
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and gemcitabine thus teaching claims 1, 7-11, 14-15, 26 and 28.
Claim 25 are directed to dosage and frequency of the dosage of compound of formula (I). Examiner interprets these attributes as variables the artisan would normally be expected to routinely optimize. For example, dosages of pharmaceuticals and frequency of the dosage are routinely optimized based on body weight and body surface area (Anisel et.al. page 50). Generally, dosage will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such attributes are critical. The specification does not indicate the dosage and frequency of the dosage to be 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) (“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). See MPEP 2144.05(II)(A).
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).
Response to Arguments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 is improperly depended on cancelled claim 13. A claim cannot depend on cancelled claim. Claim 14 is rejected under 35 U.S.C. 112(d).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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).
Conclusion
No claims are allowed as written.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Rehana Ismail whose telephone number is (703)756-4776. The examiner can normally be reached Monday-Friday 9:00am-5:00pm.
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/R.I./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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