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 .
Claim Status
Claims 1-16 and 34 are cancelled. Claims 26-31 are withdrawn. Claims 17-25 and 32-33 are pending and under examination.
Priority
This application is a national stage entry of PCT/EP2021/062729 filed on 5/12/2021, which claims priority European Patent application EP20305750.0 filed on 7/3/2020.
Objections and Rejections Withdrawn
The objections over claim 17 are withdrawn per applicant’s corrections to the claim.
The objection over claims 32-33 is withdrawn per applicant’s corrections to the claim.
The rejection under USC 112(a) for scope of enablement over claim 34 is withdrawn per applicant’s cancellation of the claim.
The rejection under USC 112(a) for scope of enablement of claims 17-25 and 32-34 is withdrawn per amendment to claim 17 and cancellation of claim 34.
The rejection under USC 112(a) for written description is withdrawn per applicant’s cancellation of claim 34.
The rejection under USC 112(b) over “such as” in claim 17 is withdrawn per applicant’s deletion of “such as” from the claim.
The rejection under USC 112(b) over the presence of two definitions of R9 in the claim is withdrawn per applicant renaming one as R9’. However, note that this brought another issue as applicant may not have changed one of the R9 recitations to R9’ in a preceding compound formulation.
The rejection under USC 112(b) over claims 18-22 is withdrawn per applicant’s amendment to claim 17 to remove “at least” from before “a compound”.
The rejection under USC 112(b) over claims 23 (and 32) is withdrawn per applicant’s deletion of “or older subjects”.
The rejection under USC 112(b) over use of “likely” in claim 24 (and claim 33) is withdrawn per applicant’s argument indicating that it relates to patients with poor prognosis while pointing to the specification.
The rejection under USC 112(b) over claims 32 and 33 for dependence to claims 23 and 24 is withdrawn.
The rejection under USC 112(b) over claim 34 is withdrawn per applicant’s cancellation of the claim.
The rejection under USC 102 over Wang is withdrawn per applicant’s amendment to cancel claim 34.
As these rejections are withdrawn, applicant’s arguments toward the rejections are now moot.
New Rejection – As Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17, and 23-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 is indefinite for reciting R9’ for a compound with a prior recitation of R9’. It is unclear if the R9 presented in the definition of the Z group option (NHNR9R10), should be read with R9’ or if the R9 in this group should be read with the previous definition given for R9 earlier in the claim. If applicant means the Z group to have a definition with NHNR9’R10, then applicant may amend this recitation so that R9’ will have basis there. For the purpose of compact prosecution, the examiner will consider this Z group option as being able to have the R9’ definition.
Claims 23-25 are rejected as being dependent on an indefinite claim without correcting this issue for item Z as this option of NHNR9R10 remains as an option of Z for those claims.
Maintained Rejection
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 17-25 are rejected under 35 U.S.C. 103 as being unpatentable over Mehrpour US 20170253610 and Roulston (Oncotarget, 2016, volume 7, pages 73448-73461).
Mehrpour teaches compounds that can treat cancer that include compounds of formula (I)
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(abstract and claim 1 of Mehrpour, claim 1 has definitions of variable groups). Mehrpour teaches in combination with a therapy against cancer like anticancer drugs and they can be concurrent or
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(paragraph 108). Mehrpour teaches
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(paragraph 206). Mehrpour teaches administration routes and administering with doses (paragraphs 95-97). Mehrpour teaches pharmaceutical carriers (paragraph 95). Mehrpour teaches Adriamycin (aka doxorubicin) and Cyclophosphamide (AC), Docetaxel (Taxol), Trastuzumab, Degarelix, Capecitabine, ifosfamide or Cis platine, advantageously Adriamycin and Cyclophosphamide (AC), Docetaxel (Taxol), as combination product for simultaneous, separate or staggered use as a medicament (paragraph 103, also claims 17 and 18 of Mehrpour). Mehrpour provides that its compounds are derivatives of salinomycin (paragraphs 1, 2, 12 and 53). Mehrpour teaches the salinomycin derivatives of its invention have superior activity against cancer stem cells and TICs (paragraph 9). AM5 was taught to decrease tumor volume and weight (paragraph 239). Mehrpour teaches “These results thus indicate that the compounds of formula (I) according to the present invention are capable of inhibiting the formation of mammospheres more efficiently than salinomycine.” (paragraphs 229-233). Mehrpour provides for prevention of cancer relapse (claim 14 of Mehrpour and paragraph 101). Mehrpour does not explicitly provide for older or unfit subjects, but it would be obvious to one of ordinary skill in the art to treat any patients, regardless of health status or age, with cancers like leukemia.
Mehrpour teaches leukemias for treatment, but does not specifically point out acute myeloid leukemia.
Roulston teaches that low dose salinomycin induces anti-leukemic responses in AML and ALL (title and abstract). Roulston teaches sensitivity of different human AML cell lines to salinomycin (figure 1). Roulston teaches anti-leukemic effects of salinomycin in primary cells (figure 6). Roulston teaches primary AML patient bone marrow and mobilized peripheral blood samples (Materials and Methods).
One of ordinary skill in the art before the time of filing would have used the salinomycin derivatives of Mehrpour to treat AML as Roulston recognizes AML as responding to salinomycin and Mehrpour recognizes its anti-cancer salinomycin derivatives have even more improved activity than salinomycin in treating cancer. Mehrpour also recognizes that leukemia can be treated with its compounds. Thus, there was a reasonable expectation of success in treating AML (a leukemia) with the salinomycin derivatives of Mehrpour including AM5 (compound that is ironomycin) and obtaining improved treatment of the AML over salinomycin.
Claims 32-33 in addition to Claim(s) 17-25 are rejected under 35 U.S.C. 103 as being unpatentable over Mehrpour US 20170253610 and Roulston (Oncotarget, 2016, volume 7, pages 73448-73461) and Konopleva et al (Blood, 2018, volume 132, pages 1007-1012).
Mehrpour and Roulston teach the claims as indicated above.
Mehrpour and Roulston do not teach Bcl-2 inhibitors in combination with the compound of Mehrpour for treatment of a cancer.
Konopleva teaches that preclinical results have spurred clinical BCL-2 inhibition in AML (abstract and table 1). Konopleva teaches venetoclax in combination with standard AML agents (abstract). Konopleva teaches targeting BCL-2 to kill cancer cells (page 1007). Konopleva teaches “On the basis of this preclinical data, a phase 2 clinical trial of venetoclax in relapsed/refractory AML (M14-212) was launched in December 2014” and that the median age of patients was 71 years old (Venetoclax monotherapy in AML, page 1010). In the conclusion, it is noted that BCL-2 targeting has emerged as an efficacious and well tolerated clinical strategy for AML (page 1011). Konopleva also recognizes an opportunity to combine with other agents in AML (page 1011).
One of ordinary skill in the art before the time of filing would have included Bcl-2 inhibitors with the treatments motivated by Mehrpour and Roulston as these agents were seen as targeting cancer cells in leukemia including AML. There would be a reasonable expectation of success in increased treatment of the AML through a combination of the salinomycin derivatives including ironomycin of Mehrpour known for leukemias having direction of Roulston for AML treatment, with the BCL-2 inhibitors of Konopleva also known for AML (a leukemia). Each of Konopleva and Mehrpour also recognize combining the drugs with other anti-cancer agents to increase efficacy.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The 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 17-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23, 24 and 27 of U.S. Patent No. 10287298 in view of Mehrpour US 20170253610 and further in view of Roulston (Oncotarget, 2016, volume 7, pages 73448-73461).
The claims overlap as the claims of ‘298 utilize compounds of formula (I) in order to treat cancer in subjects while the claims of applicant’s application provide for using such a compounds in AML, which is a species of cancer.
‘298 claims do not provide for AML or the combination with another anti-cancer drug as in applicant’s claims.
Mehrpour teaches compounds that can treat cancer that include compounds of formula (I)
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(abstract and claim 1 of Mehrpour, claim 1 has definitions of variable groups). Mehrpour teaches in combination with a therapy against cancer like anticancer drugs and they can be concurrent or
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(paragraph 108). Mehrpour teaches
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(paragraph 206). Mehrpour teaches administration routes and administering with doses (paragraphs 95-97). Mehrpour teaches pharmaceutical carriers (paragraph 95). Mehrpour teaches Adriamycin (aka doxorubicin) and Cyclophosphamide (AC), Docetaxel (Taxol), Trastuzumab, Degarelix, Capecitabine, ifosfamide or Cis platine, advantageously Adriamycin and Cyclophosphamide (AC), Docetaxel (Taxol), as combination product for simultaneous, separate or staggered use as a medicament (paragraph 103, also claims 17 and 18 of Mehrpour). Mehrpour provides that its compounds are derivatives of salinomycin (paragraphs 1, 2, 12 and 53). Mehrpour teaches the salinomycin derivatives of its invention have superior activity against cancer stem cells and TICs (paragraph 9). AM5 was taught to decrease tumor volume and weight (paragraph 239). Mehrpour teaches “These results thus indicate that the compounds of formula (I) according to the present invention are capable of inhibiting the formation of mammospheres more efficiently than salinomycine.” (paragraphs 229-233). Mehrpour provides for prevention of cancer relapse (claim 14 of Mehrpour and paragraph 101). Mehrpour does not explicitly provide for older or unfit subjects, but it would be obvious to one of ordinary skill in the art to treat any patients, regardless of health status or age, with cancers like leukemia.
Mehrpour teaches leukemias for treatment, but does not specifically point out acute myeloid leukemia.
Roulston teaches that low dose salinomycin induces anti-leukemic responses in AML and ALL (title and abstract). Roulston teaches sensitivity of different human AML cell lines to salinomycin (figure 1). Roulston teaches anti-leukemic effects of salinomycin in primary cells (figure 6). Roulston teaches primary AML patient bone marrow and mobilized peripheral blood samples (Materials and Methods).
One of ordinary skill in the art before the time of filing in light of the claims of US
‘298 would have used the salinomycin derivatives of Mehrpour to treat AML as Roulston recognizes AML as responding to salinomycin and Mehrpour recognizes its anti-cancer salinomycin derivatives have even more improved activity than salinomycin in treating cancer and provided compositions as in applicant’s claims with an anti-cancer drug. Mehrpour also recognizes that leukemia can be treated with its compounds. Thus, there was a reasonable expectation of success in treating AML (a leukemia) with the salinomycin derivatives of Mehrpour including AM5 (compound that is ironomycin) and obtaining improved treatment of the AML over salinomycin.
Response to Applicant’s Arguments over the Rejections under USC 103 and Non-Statutory Double Patenting
Applicant argues that although Mehrpour provides ironomycin and general teaching of leukemia as one of the cancers its compounds can treat, it does not particular point out AML which is a more specific leukemia. Applicant argues (A) that Mehrpour’s general disclosure cannot obviate AML as it does not mention AML while Roulston’s related compound (salinomycin) for treating AML is not the compound of the claims. It is argued there would be no expectation of combining the references to treat AML with Mehrpour’s compounds. The examiner disagrees. Mehrpour is able to treat cancer with its compounds with citing leukemia as one subset. Leukemia would include AML as one species. Furthermore, Mehrpour recognizes its compounds are derivatives of salinomycin (paragraphs 1, 2, 12 and 53) while Roulston recognizes effectiveness of salinomycin to treat AML. There is a reasonable expectation of success in using beneficial derivatives of salinomycin (based on the active salinomycin) known to treat cancers including leukemias in teachings of Mehrpour and use them for treating AML (a leukemia) when salinomycin has been shown to be effective for AML by Roulston.
Applicant next argues in (B) that there is a lack of motivation and reasonable expectation of success and that the rejection relies upon hindsight reconstruction. As mention in response to argument (A), there is a reasonable expectation of success in combining the teachings of Mehrpour and Roulston to treat AML (a leukemia) with derivatives of salinomycin taught in Mehrpour which treat cancers including leukemias, particularly when salinomycin is noted as effective for AML.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The rejection under USC 103 over Mehrpour and Roulston is maintained.
Applicant argues that the rejection under USC 103 over Mehrpour, Roulston and Konopleva does not remedy the deficiencies of Mehrpour and Roulston. As mentioned above, the rejection over Mehrpour and Roulston is maintained for reasons discussed. Applicant argues that ironomycin has striking effects on AML cells and that applicant describes better response when ironomycin is combined with the BH3 mimetic (e.g. venetoclax). At the moment the claims are broad and not specific to ironomycin. The genus for the Y portion of the compound is broad even in claims 32 and 33 to cover many more compounds other than ironomycin. Claims 32 and 33 also cover other compounds besides BH3 mimetics in combination with the compound of formula I. Thus, as there is a reasonable expectation of success in combining the prior art to use such combinations of compounds provided by the claims and treating AML with such compounds, there remains the reasonable expectation of treatment of AML. Perhaps the claims may be amended to be in reasonable scope with the results that applicant sees as substantial enhancement of effectiveness in treating AML. However, at the moment, the rejection under USC 103 over Mehrpour, Roulston and Konopleva is maintained.
Applicant argues that as Mehrpour and Roulston cannot teach the claims, the rejection under double patenting of US patent 10,287,298 including Mehrpour and Roulston would also not provide for non-statutory type double patenting. As motivations of Mehrpour and Roulston would obviate the treatment of AML with such compounds as discussed above in this response to arguments, this rejection is maintained.
Conclusion
No claims are allowed.
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 MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached on (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613