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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 17 July 2025, have been entered in full. Claims 2-4, 6-15, 18, 22-24, 26-78, 80 and 81 are canceled. Claim 1 is amended. Claims 1, 5, 16, 17, 19-21, 25, 79, 82-84 are under examination.
Withdrawn Objections And/Or Rejections
The rejection to claims 1, 5, 16, 17, 19-21, 25, 79, 82 and 84 under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov (Identifier NCT02363491) as evidenced by as evidenced by Opsona Therapeutics Limited (EP 2722342; published 10/19/12) in view of Kirschning et al. (US 2014/0343256; published 11/20/14, priority date 9/23/04) and Braun et al. (Best Practice & Research Clinical Haematology 26:327-336, 2013), as set forth at pages 2-10 of the previous Office Action (19 February 2025), is withdrawn in view of the amendment and Applicant's arguments. Applicant states that the claims, as amended, recite the population to be treated is subjects with higher risk MDS based on the IPSS.
Applicant argues that that there is no suggestion in the Clinical Trail document or in the additional cited art to treat the population higher risk for MDS based on the IPSS. In addition, Applicant states that the treatment of subjects with higher risk MDS based on the IPSS was specifically excluded from the Clinal trial (listed in the exclusion criteria)(17 July 2025).
The rejection to claim 83 under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov Identifier NCT02363491 as evidenced by as evidenced by Opsona Therapeutics Limited in view of Kirschning et al. and Braun et al., as applied to claim 1 above, and further in view of Wei et al. (Toll-like receptor alterations in myelodysplastic syndrome Leukemia Vol. 27:1832-1840; 2013), is withdrawn in view of the amendment and Applicant's arguments (as discussed above)(17 July 2025).
NEW CLAIM REJECTIONS/OBJECTIONS
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 16, 17, 19-21, 25, 79, 82-84 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification teaches methods for the treatment of Myelodysplastic Syndrome, in particular subjects who have been shown to be refractory or resistant to treatments such as treatments with hypomethylating agents comprising administering a therapeutically effective amount of a Toll-like receptor 2 (TLR2) antagonist to said subject (page 1 and page 3). The specification teaches antibodies that are TLR2 antagonist (pages 8-10).
The Examples teach a study was carried out that evaluated the safety, tolerability and efficacy of antibody OPN-305 in patients with lower-risk (low and intermediate-1) MDS for who previous treatment with or without erythroid-stimulating agents or azacitidine or decitabine failed (page 43). The Examples teach a total of 15 patients were enrolled. Three patients were classified as Low risk and 12 patients were classified as Intermediate-1 risk by IPSS (page 44). The Examples teach treatment with OPN-305 in patients with previously treated lower-risk MDS was well tolerated with no significant toxicities and 50% overall response rate (page 49).
The claims are not enabled for the following reasons:
1. The specification fails to teach treating subjects with higher risk myelodysplastic syndrome (MDS) as characterized by international prognostic scoring system (IPSS) who are refractory or resistant to previous treatment with a hypomethylating agent.
As was stated above, the Examples teach administering OPN-305 to patients with lower-risk (low and intermediate-1) who are refractory or resistant to previous treatment with a hypomethylating agent.
Given this guidance, one of ordinary skill in the art could reasonably predict that administering OPN-305 would be useful in methods for treating lower-risk (low and intermediate-1) MDS in a subject who is refractory or resistant to previous treatment with a hypomethylating agent.
The Examples fail to teach treating a higher-risk MDS population. Therefore, it cannot be said that the instant specification provides the necessary guidance.
It is well known in the art that lower-risk (low and intermediate-1) MDS is vastly different from higher risk (intermediate-2 or high-risk) MDS.
Apuri et al. teach that patients classified as having lower risk disease (low or
intermediate-1 IPSS risk) are considered to have lower risk MDS (LR-MDS), and the goal of therapy is to alleviate cytopenia and reduce transfusions. The options for therapy include erythroid stimulating agents (ESAs), immunosuppressive therapy, lenalidomide, and hypomethylating agents (HMAs). Apuri et al. teach that patients with higher risk MDS (HR-MDS; intermediate-2 or high-risk IPSS) have a poor prognosis with short estimated overall survival (OS). Apuri et al. teach the primary goal in the treatment of HR-MDS is to prolong OS and extend the interval to progression to AML. Apuri et al. teach the treatment options include allogeneic hematopoietic stem cell transplantation, which remains the only curative treatment option for MDS, and HMAs. Apuri et al. teach azacitidine and decitabine are the 2 HMAs approved for management (pages 211-212)(Evidence for Selective Benefit of Sequential Treatment With Hypomethylating Agents in Patients With Myelodysplastic Syndrome. Clinical Lymphoma, Myeloma & Leukemia, Vol. 17, No. 4, 211-214, Jan 10 2017).
Prebet et al. teach that azacitidine (AZA) is the current standard of care for high-risk (i.e., International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. Prebet et al. teach that the outcome after AZA failure is poor. Prebet et al. teach that allogeneic transplantation remained the option with the best outcome, with long-term survival in a substantial proportion of patients even if some patients underwent transplantation with progressive disease (pages 3322-3323 and page 3326)(Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure. Journal of Clinical Oncology, Volume 29/Number 24, pages 3322-3327; August 2011).
It would be highly unpredictable the effects, if any, OPN-305 would have when administered to higher-risk MDS subjects who are refractory or resistant to previous treatment with a hypomethylating agent.
Due to the inherent unpredictability of administering OPN-305 to higher-risk MDS subjects who are refractory or resistant to previous treatment with a hypomethylating agent; the lack of guidance in the specification regarding same; the absence of working examples directed to same; the complex nature of the invention and the state of the art which teaches that treatment options for higher-risk MDS subjects include HMAs and/or allogeneic hematopoietic stem cell transplantation; undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
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.
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/ELIZABETH C. KEMMERER/ Primary Examiner, Art Unit 1674
/R.M.D/Examiner, Art Unit 1647 8/12/2025