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 .
Application and Claims Status
In the amendment as filed on 6/6/2026, applicants have amended claims 8, 10, 11, and 13; cancelled no claims; and added no new claims. Therefore, claims 8-20 are currently pending and claims 8-20 are presently under examination. Additionally, the present specification is amended in order to correct for typographical errors, run-on sentences, subject-verb agreement problems, and any other possible minor errors.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 4/28/2026 is in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Claim Objections
The objections to the specification (abstract and disclosure) and claims are withdrawn based on
Applicant’s amendments.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 8-20 under AIA 35 U.S.C. 112(b) is withdrawn based on Applicant’s
amendments.
Claim Rejections - 35 USC § 112(a)
The rejection of claims 8-20 under AIA 35 U.S.C. 112(a) (Written Description) is withdrawn based on Applicant’s amendments. Applicant has removed the term “prodrug” from the claims.
The rejection of claims 8-20 under AIA 35 U.S.C. 112(a) (Enablement-Method of Treating with Compounds) is withdrawn based on Applicant’s amendments and arguments. Examiner agrees with Applicant that “a skilled person in the art can routinely prepare additional compounds within the scope of Formula I” and that the “specification provides sufficient guidance to make and use compounds across the scope of amended claim 8 without undue experimentation” (Remarks, Page 12).
The rejection of claims 8-20 under AIA 35 U.S.C. 112(a) (Enablement-Prevention) is withdrawn based on Applicant’s amendments and arguments. Examiner agrees with Applicant that the claims are directed to “treatment of myelofibrosis and associated symptoms or signs, not prevention” (Remarks, Page 13).
Claim Rejections - 35 USC § 103
Applicant’s arguments of the rejection of claims 8-20 under AIA 35 U.S.C. 103 are not found
persuasive and the rejection is maintained based on Applicant’s arguments.
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) 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (US 2020/0385408 A1, published 12/10/2020, cited on IDS filed on 12/20/2023)(hereinafter, ‘Xu’) and Senderowicz et al. (US 10,918,646 B1, published 02/16/2021, cited by Examiner on 3/6/2026)(hereinafter, ‘Senderowicz’).
The instant application claims methods of treating myelofibrosis by providing and administering a medicament comprising compounds of formula I, shown below. A specific claimed species, and synthesis thereof, is Compound 1, taught in Example 1, on pages 17-19, also shown below:
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Xu teaches the exact species of compound 1 above on page 6, para 0101, labeled ‘Compound 19’. Xu additionally teaches other examples that read on the genus of instant formula I in reference Table 4 (page 13-16). Xu teaches that these compounds are useful as bromodemain inhibitors, especially BRD4 inhibitors, and their use in the treatment of bromodemain and extra-terminal domain (BET)-mediated diseases in Example 1, which shows the inhibitory activity of reference compounds against BRD4 (page 41-42, para 0321-0326) and Example 2, which shows pharmacokinetic data (page 42, para 0327). Further, Xu teaches oral administration of reference compounds with dose ranges between 1 mg to 100 mg (page 42, para 0328-0329).
Xu does not teach a method of using these compounds to treat myelofibrosis.
Senderowicz teaches a method of treating myelofibrosis in a subject using reference compound 1 (CPI-0610) and teaches that reference compound 1 is an inhibitor of the BET family (col 5, lines 27-55; col 13, lines 61-67 and col 14 lines 1-22; and elsewhere).
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to take the BET inhibitor compounds of Xu and apply it to methods of treating myelofibrosis described by Senderowicz with a reasonable expectation of success. One of ordinary skill would find motivation in that Senderowicz teaches BET inhibitors that treat myelofibrosis in human subjects.
Thus, said claims are rendered obvious.
Applicant traverses the rejection by asserting (Remarks, page 14):
Senderowicz et al. reports activity for a single reference compound (CP1-0610), but
does not disclose or suggest the compounds of Formula I, nor does it provide any
teaching that the observed activity would extend to structurally distinct BET inhibitors.
Based on the teachings of Senderowicz et al., a skilled artisan would understand only
that the specifically disclosed compound (CP1-0610) demonstrated activity in treating
myelofibrosis. Senderowicz et al. does not provide any teaching or suggestion that such
activity would extend broadly to other BET inhibitors, much less to the structurally
distinct compounds of Formula I disclosed by Xu et al. Accordingly, even if a person of
ordinary skill in the art were motivated to combine the references, there would have
been no reasonable expectation of success that the compounds of Formula I would be
effective for treating myelofibrosis.
Examiner does not find this persuasive. According to MPEP 2145(IV): One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually.
Furthermore, Applicant purports that there would not have been a reasonable expectation of success that the compounds of instant application would be effective for treating myelofibrosis. According to MPEP 2143.02, “the reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention.” Examiner contends that there is, indeed, a reasonable expectation of success that the combined teachings of the prior art would be obvious. The compounds of the instant application are taught by Xu as known bromodomain inhibitors, especially BRD4 inhibitors, and their use in the treatment of BET-mediated diseases. Senderowicz teaches a known BET-inhibitor (Compound 1), and its application in the treatment of myelofibrosis. Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to take the BET inhibitor compounds of Xu and apply it to methods of treating myelofibrosis described by Senderowicz with a reasonable expectation of success.
New Objections/Rejections
Claim Objections
(Not Necessitated by Claim Amendment)
Claim 8 is objected to because of the following informality: the term “comprising” in “wherein the method comprising” should be replaced with “comprises”. Appropriate correction is required.
Claim 20 is objected to because of the following informality: there are additional spaces between the “5mg/ day, or 20mg/ day”. This occurs repeatedly throughout the claim where, in almost all instances, there is a gap between the amount (in mgs) and the “per day” component. Appropriate correction is required.
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 8 and 10 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.
Claims 8 and 10 are rejected as vague and indefinite for their recitation, in the limitation of Q that “Q is absent”, and in the limitation of R3 that “R3 is absent”. If said variables are “absent”, then there would not be variables at these positions. Examiner recommends amending the claims to read, “Q is a bond” and “R3 is a bond” if that is what Applicant intends.
Claim Rejections - 35 USC § 103
(Not Necessitated by Claim Amendment)
The statute has been previously cited in the first appearance of “Claim Rejections - 35 USC § 103” above.
Claim(s) 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (WO 2019/120234 A2, published June 27, 2019, cited on IDS filed on 12/20/2023)(hereinafter, ‘Xu 2019’) and Senderowicz.
The instant application claims methods of treating myelofibrosis by providing and administering a medicament comprising compounds of formula I, shown below. A specific claimed species, and synthesis thereof, is Compound 1, taught in Example 1, on pages 17-19, also shown below:
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Xu 2019 teaches the exact species of compound 1 above on page 23, labeled ‘Compound 19’. Xu 2019 additionally teaches other examples that read on the genus of instant formula I in reference Table 4 (page 13-16). Xu 2019 teaches that these compounds are useful as bromodemain inhibitors (Abstract), especially BRD4 inhibitors, and their use in the treatment of bromodemain and extra-terminal domain (BET)-mediated diseases in Table 8, which shows the inhibitory activity of reference compounds against BRD4(D1) and BRD4(D2) (page 43, para [0449-0450]) and Table 9, which shows pharmacokinetic data (page 44, para [0455]). Specifically, compound 19 is illustrated as a potent inhibitor of BRD4(D1) and BRD4(D2), and its pharmacokinetic data is also highlighted. Further, Xu 2019 teaches oral administration of reference compounds with dose ranges between 1 mg to 200 mg (page 44, para [0457]).
Xu 2019 does not teach a method of using these compounds to treat myelofibrosis.
Senderowicz teaches a method of treating myelofibrosis in a subject using reference compound 1 (CPI-0610) and teaches that reference compound 1 is an inhibitor of the BET family (col 5, lines 27-55; col 13, lines 61-67 and col 14 lines 1-22; and elsewhere).
Therefore, it would have been prima facie obvious at the time of the effective filing date for one of ordinary skill in the art to take the BET inhibitor compounds of Xu 2019 and apply it to methods of treating myelofibrosis described by Senderowicz with a reasonable expectation of success. One of ordinary skill would find motivation in that Senderowicz teaches BET inhibitors that treat myelofibrosis in human subjects.
Thus, said claims are rendered obvious.
Double Patenting
(Not Necessitated by Claim Amendment)
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 8-12, 16-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 20 of U.S. Patent No. 11,466,034. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of treating myelofibrosis of instant independent claim 8 overlaps in claimed matter with claim 20 of the issued U.S. patent.
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 also 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).
Here, the same compounds of formula I are recited in both the instant application and the patent. The disclosure of the patent (col. 2 lines 9-14) recites “the present invention relates to compounds as bromodomain inhibitors, especially BRD4 inhibitors, and their use in the treatment of BET-mediated diseases” employing compounds of reference formula I, which read on the compounds of instant application and also recites (claim 6) " wherein the BET-mediated disease is selected from the group consisting of selected from the group consisting of β acute lymphoblastic leukemia, Burkitt's lymphoma, diffuse large β-cell lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, follicular lymphoma, primary plasma cell leukemia, large cell neuroendocrine carcinoma, colon cancer, rectal cancer, mantle cell lymphoma, multiple myeloma, breast cancer, prostate cancer, glioblastoma tumor, squamous cell esophageal cancer, liposarcoma, melanoma, pancreatic cancer, brain cancer, and lung cancer”.
The ordinary artisan would recognize as obvious that determination of whether said disease or condition is treatable with an inhibitor of BET is present in the instant claims, is implicit in the patented claim in view of Sun Pharmaceutical Industries, LTD. v. Eli Lilly and Company which states the following: “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see 5,563,165 (“’165 patent”), at [57], col.1 11.11-14, col.3 11.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 1.49- col. 108 1.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.
Claims 8-12, 16-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of U.S. Patent No. 11,845,762. Although the claims at issue are not identical, they are not patentably distinct from each other because the methods of treating myelofibrosis of instant independent claims 8 overlap in claimed matter with claim 6 of the issued U.S. patent.
The exact same reasoning from the previous NSDP rejection is applied here.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
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/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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