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 .
CONTINUING DATA
This application is a 371 of PCT/US2020/038760 06/19/2020
PCT/US2020/038760 has PRO 62/864,413 06/20/2019
This office action is in response to Applicant’s amendment submitted March 4, 2026. Claims 1, 6-17, 20-25, 27, and 29-33 are pending. Applicant’s election without traverse of the species venetoclax in the reply filed on December 17, 2024 is acknowledged.
The following new or modified rejections were necessitated by Applicant’s amendment to claim 1, which requires a dose of about 200 mg or about 300 mg. This limitation was previously recited as an option in claim 9, but claim 9 did not require it because claim 9 recited limitations linked by “and/or” (so only one of (a)-(f) was required). The amendment also creates new combinations of limitations since a limitation from a dependent claim was moved into the independent claim upon which other claims depend.
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 9 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 9 depends from claim 1. Claim 1 as amended requires administration of AZA at a dose of about 200 mg or about 300 mg. Claim 9, however, recites that the dose of about 200 mg or about 300 mg is optional because the limitations of (a)-(e) are given in and/or form. If (c), (d), or (e) is met, then (a) and (b) are not necessary because of the “or” language. Claim 9 fails to require the limitations of claim 1. 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.
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.
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, 6-17, 20-25, 27, and 29-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over DiNardo (Lancet Oncol., vol. 19(2), pp. 216-228, January 2018, cited on IDS) in view of Cogle (The Oncologist 2015;20:1404-1412, cited on IDS) and Etter (US 8846628B2, 2014, cited on IDS).
It is noted that 5-azacytidine is also known as azacytidine or azacitidine.
DiNardo teaches a method of treating AML comprising oral administration of venetoclax and subcutaneous or intravenous azacytidine 75 mg/m2 (days 1-7 of each 28-day cycle). Venetoclax synergizes with azacytidine. See Introduction. The dose of venetoclax was 400 mg, 800 mg, or 1200 mg. The regiment was well-tolerated and 60% of patients achieved remission. See abstract. Oral administration of venetoclax began on day 2 of cycle 1, which meets the limitation of claims 22-25, 27, and 29-30 when azacytidine is administered for one day, then venetoclax is administered for one day, then optionally repeating. Page 3, right column, first full paragraph.
DiNardo does not teach oral administration of azacytidine and does not teach treatment of MDS.
Cogle teaches that azacytidine can be administered orally for treating of MDS or AML. See abstract. Dosing of azacytidine was 120-600 mg/day for 7 days or 200 mg for 14 days. Page 1407, Figure 2. Multiple cycles were carried out. Page 1406, last two paragraphs. Oral administration of azacytidine avoids injection-site reactions and may enhance patient convenience. Page 1406, end of first column. Oral administration also allows for alternative doses and extended dosing schedules, which may decrease toxicity and increase efficacy. Page 1406, top of right column. The MTD of oral azacytidine was 480 mg on days 1-7 of a 28-day cycle, but lower doses allowed for extended low-dose administration over periods of 14 or 21 days. See Conclusion. 7-day oral azacytidine dosing was clinically active. Page 1407, end of left column. Azacitidine for injection is approved for high-risk MDS according to IPSS (page 1405, left column).
Etter teaches a non-enteric coated tablet containing 5-azacytidine (claim 1). The amount of 5-azacytidine is 120 to 480 mg (claim 23) or about 300 mg (claim 24). The composition is used for treating myelodysplastic syndrome or acute myelogenous leukemia (claim 28). The composition can be used along with an additional therapeutic agent (column7, lines 45-50).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to treat AML or MDS using a combination of venetoclax and oral azacytidine because oral administration of azacytidine avoids injection site reactions and is convenient. Both AML and MDS are treated using azacytidine and azacytidine synergizes with venetoclax, so the skilled artisan would have employed the combination. The skilled artisan either would have substituted the iv azacytidine in DiNardo’s method with oral azacytidine for convenience, or would have added venetoclax to Cogle’s or Etter’s methods to achieve a synergistic treatment. The skilled artisan would have had a reasonable expectation of success because oral azacytidine is effective as taught by Cogle and Etter. It would have been obvious to treat a high-risk MDS patient because azacytidine is approved for high-risk patients and Cogle teaches that relatively high amounts (480 mg) of oral azacytidine can be tolerated.
The limitations of claim 20 are inherent properties of the combination of azacytidine and venetoclax. Limitations (f)-(n) in claim 21 are inherent properties of administration of azacytidine.
Response to Arguments
Applicant argues that claim 1 does not require a non-enteric coated tablet form, so Etter’s disclosure of a non-enteric coated tablet is not relevant to current claim 1, and so Applicant requests the examiner to withdraw the rejection of claim 1 or provide revised claim mapping. This argument is not persuasive. Etter teaches a non-enteric coated tablet in claim 1, so the limitation is properly mapped to the reference.
Applicant argues that the cited references do not provide a reason or motivation to combine oral AZA with venetoclax. This argument is not persuasive because the art teaches administration of the combination of venetoclax and subcutaneous or intravenous AZA (DiNardo), and the art teaches that AZA can instead be administered orally to avoid injection site reactions and enhance patient convenience (Cogle), and oral AZA can be combined with other therapies (Etter). The skilled artisan would have employed oral AZA instead of intravenous/subcutaneous AZA in order to achieve the advantages of oral AZA taught in the prior art, or would have added venetoclax to Cogle’s method to achieve the advantage of a synergistic treatment. MPEP 2144.04 states that the expectation of some advantage is the strongest rational for combining prior art references.
Applicant argues that Etter does not teach the combination of oral AZA with venetoclax. This argument is not persuasive because the motivation to combine oral AZA with venetoclax is found in DiNardo. DiNardo teaches that venetoclax synergizes with azacytidine.
Applicant argues that the field is highly unpredictable because oral absorption depends on multiple factors as taught in Exhibit I and oral and non-oral routes of administration are fundamentally different as taught in Exhibit 2. Applicant further argues that it is not routine to identify an oral dosage form that will work synergistically with venetoclax. These arguments are not persuasive because the art already discloses an effect oral form of AZA which can be used for the same purpose as injectable AZA. The rejection does not state that it would have been obvious to develop a new oral dosage form of AZA, only that it would have been obvious to use the oral dosage form of AZA which is already known in the art to be effective for treating the same diseases as injectable AZA (AML or MDS).
Applicant argues that it was Applicant who appreciated the advantages of orally administered AZA in combination with venetoclax, which include better patient experience and reduced risk of hospital infections. This argument is not persuasive because Cogle also mentions advantages of oral administration, including patient convenience and lack of injection site reactions. The better patient experience and reduced risk of infection are not unexpected.
The following rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 6-17, 20-25, 27, and 29-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of copending Application No. 17/620,545 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims treating AML using azacytidine and another agent (claim 1), wherein the additional agent is venetoclax (claim 15), and wherein the azacytidine is administered orally in the form of a non-enteric coated tablet (claim 9). The agents can be administered concomitantly or sequentially (claim 3), and can be in one dosage form or separate (claim 4). Azacytidine can be administered at a dose of about 200 mg (claim 8) for 14 days in a 28-day cycle (claim 10). Azacytidine can be administered orally daily for 1, 2, 3, etc. days followed by an optional treatment holiday of 14 days (claims 11-12).
The reference claims also require administration of an LSD-1 inhibitor, which is not required by the current claims. The current claims do not exclude administration of the LSD-1 inhibitor. The reference claims anticipate the current claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant requested to defer this issue until the application is otherwise in condition for allowance.
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 LAYLA D BERRY whose telephone number is (571)272-9572. The examiner can normally be reached 7:00-3:00 CST, M-F.
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/LAYLA D BERRY/Primary Examiner, Art Unit 1693
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