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 .
Status of Claims
Claims 1 and 7-8 are pending.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/CN2021/102607, filed 6/28/2021. Acknowledgment is made of applicant's claim for foreign priority based on an application CN202010668274.3 filed on 7/13/2020.
Information Disclosure Statement
All references from IDS(s) received 01/13/2023 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered and have been found not persuasive.
In a non-final dated 10/16/2025, Claims 1-8 were examined upon their merits.
In a non-final dated 10/16/2025, Claims 1-8 were rejected 35 U.S.C. 102, 103 and 112. The Applicant amended claims 1 and 7-8 and cancelled claims 2-6.
With respect to the 112 rejection, the Applicant amended the claims to strikethrough any phrasing including “an analog or a derivative thereof” and therefore the 112 rejection is moot and withdrawn.
With respect to the 102 rejection, the Applicant amended independent claim 1 to require the myeloproliferative neoplasms to have ruxolitinib resistance. The 102 prior art used by the Examiner does not teach this limitation. Therefore, the 102 rejection is moot and withdrawn.
With respect to the 103 rejection, the Applicant argues that Barrio fails to teach myeloproliferative neoplasms with ruxolitinib resistance and the secondary reference provided by the Examiner (“Harrison”) fails to remedy deficiency. The Applicant argues that the Examiners previous argument that sorafenib can act as a JAK2 inhibitor, as she said was taught by Barrio, was a misunderstanding. Therefore, the Applicant argues that sorafenib is not a JAK2 inhibitor and it would not be obvious to a person skilled in the art to extract the teachings of Harrison, that a JAK2 inhibitor improves ruxolitinib resistance, and apply sorafenib. The Examiner argues that although sorafenib is indeed a RAF kinase inhibitor and not a direct JAK2 inhibitor, it is known that sorafenib can inhibit JAK indirectly. The Examiner introduces a tertiary reference del Campo, S. et al. (J Immunol. 2015 Aug 3;195(5):1995–2005). Del Campo teaches that sorafenib inhibits JAK-STAT signal transduction. Specifically, del Campo proposes that sorafenib inhibits cytokine-induced JAK-STAT activation via inhibition of JAK (Discussion, Para. 3). Therefore, the Examiner maintains her argument that because inhibition of JAK-STAT seemingly improves ruxolitinib resistance, as taught by Harrison, it would be obvious to use sorafenib to treat myeloproliferative neoplasms having ruxolitinib resistance. Therefore, the 103 rejection is maintained.
NEW/MAINTAINED REJECTIONS
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.
Claims 1 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Barrio, S. et al. (British Journal of Haematology, 2013, 161, 667–676; “Barrio”) in further view of Harrison, C. et al. (Ann Hematol. 2020 Mar 20;99(6):1177–1191.; “Harrison”) and del Campo, S. et al. (J Immunol. 2015 Aug 3;195(5):1995–2005; “del Campo”) as evidenced by the Bristol-Myers Squibb Package Insert (https://packageinserts.bms.com/pi/pi_inrebic.pdf) and Fogelman, D. et al. (Cancer Med. 2018 Aug 19;7(11):5382–5393.; “Fogelman”).
Barrio teaches sorafenib as a potential treatment for myeloproliferative neoplasms (MPNs) (Abstract) including assessment of patients with polycythemia vera (Introduction, first para.), as required by instant claims 1. Barrio also teaches the ability of sorafenib to inhibit the proliferation of (Abstract and Fig 2), as well as promote the apoptosis of HEL cells (Suppl. Fig 2C).
Barrio also teaches a synergistic effect between sorafenib and ruxolitinib, but fails to teach treating ruxolitinib-resistant MPNs with sorafenib.
Harrison teaches that JAK2 inhibitors, such as fedratinib, pacritinib, and momelotinib, have been shown to induce clinical responses in patients with ruxolitinib resistance. Harrison also teaches the patients with ruxolitinib-resistant MPNs may be secondary to polycythemia vera (Introduction, para. 1). Harrison also teaches the oral administration of fedratinib being used as a medicament (Table 2), as required by instant claim 8. Finally, Harrison teaches the FDA approved version of fedratinib is INREBIC ® which includes excipients such as silicified microcrystalline cellulose and sodium stearyl fumarate, as evidenced by the BMS Package insert (Page 5, “Description” section).
Harrison fails to teach sorafenib. However, Barrio teaches sorafenib as a possible JAK2 inhibitor. Along the same line, Del Campo teaches that sorafenib inhibits JAK-STAT signal transduction. Specifically, del Campo proposes that sorafenib inhibits cytokine-induced JAK-STAT activation via inhibition of JAK (Discussion, Para. 3). Therefore, because inhibition of JAK-STAT seemingly improves ruxolitinib resistance, as taught by Harrison, it would be obvious to use sorafenib to treat myeloproliferative neoplasms having ruxolitinib resistance. Therefore, because sorafenib can inhibit the same pathway as fedratinib, as well as due to its synergistic effects with ruxolitinib, a person skilled in the art would be motivated to extract the method of Barrio and apply the teachings of Harrison to arrive at the current invention. The logic applies to regorafenib, which is known as a multi-kinase inhibitor that has been FDA approved for treating patients who were previously treated with sorafenib and also has a synergistic effect with different types of cancer, as evidenced by Fogelman.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of 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.
Applying KSR example rationale (A), it would have been prima facie obvious to extract the method of Barrio and use sorafenib to treat ruxolitinib-resistant MPN, as well as administer sorafenib as a medicament, based on the teachings of Harrison. A person skilled in the art would be motivated to do so because Harrison teaches JAK2 inhibitors as medicaments to treat ruxolitinib-resistant MPN and sorafenib works to inhibit JAK2. Therefore, claims 1 and 7-8 would be obvious to a person skilled in the art at the time.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the method of Barrio and substitute sorafenib for different JAK inhibitors, as taught by Harrison. A person skilled in the art would be motivated to do so because Harrison teaches JAK2 inhibitors as medicaments to treat ruxolitinib-resistant MPN and sorafenib works to inhibit JAK, as taught by del Campo. Therefore, claims 1 and 7-8 would be obvious to a person skilled in the art at the time.
Conclusion
Claims 1 and 7-8 are rejected.
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 NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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