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 27 October 2025, have been entered in full. Claims 2, 10, 11, 13-18, 20-23, 25-28 are canceled. Claims 1, 5, 12, 19, 31 and 32 are amended. Claims 1, 3-9, 12, 19, 24, 29-32 are under examination.
Withdrawn Objections And/Or Rejections
The rejection to claim 5 under 35 U.S.C. 103 as being unpatentable over Platzbecker et al. (The Lancet Oncology. Volume 18, Issue 10, pages 1338-1347; submitted online September 1, 2017) in view of Wang et al. (Leukemia Vol. 20:1641- 1644; 2006) and Attie et al. (WO 2016/183280; published 17 November 2016; Attie ‘280), as set forth at pages 7-8 of the previous Office Action (7/28/2025) is withdrawn in view of the amendment that recites “wherein the subject is RBC transfusion-dependent” (27 October 2025). Platzbecker et al. teach “high transfusion burden” and “low transfusion burden”, but it is not clear if these limitations fall within the scope of “RBC transfusion-dependent” as currently recited in amended claim 5. Please see the New Claim Rejections, below.
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 32 remain rejected under 35 U.S.C. 103 as being unpatentable over Attie et al. (US 2016/0289286; published 06 October 2016; Attie ‘286) in view of Attie et al. (WO 2016/183280; published 17 November 2016; Attie ‘280).
The basis for this rejection is set forth at pages 3-7 of the previous Office Action (28 July 2025).
APPLICANT’S ARGUMENTS: Applicant discusses the legal standard of obviousness. Applicant repeats arguments which are of record (present arguments dated 6/28/2024).
Applicant submits that claims 1 and 32 are not obvious over Attie ’286 in view of Attie ’280. Applicant states that without conceding to the merits of the rejection, and without prejudice or disclaimer, claim 1 is amended herein to recite that "the subject is refractory to, intolerant to, or ineligible for erythropoiesis-stimulating agent (ESA) treatment."
Applicant argues that the Patent Office contends that Attie ‘286 teach experiments to examine the effects of luspatercept on anemia in patients with low or Int-risk MDS patients who are nonresponsive/refractory to ESAs (Office Action, page 13). Applicant states that patients are classified in Example 23 of Attie '286 as follows: 15% RARS, 46% RCMD-RS, 15% RCMD, 15% RAEB-1 and 8% del (5q). Applicant directs the Examiner’s attention to Attie '286 at paragraph [00452]. Applicant argues that Attie '286 does not explicitly identify any of the patients in Example 23 as classified as RARS-T or as having a platelet count of higher than 400 X 10⁹/L. Applicant argues that Attie '286 does not state that a subject that has a baseline platelet count of higher than 400 X 10⁹/L AND is refractory to, intolerant to, or ineligible for ESA treatment, can be treated according to the claimed methods. Applicant argues that Attie '280 does not remedy this deficit.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. Applicant’s argument that patients classified in Example 23 [para 00452] of Attie '286 are 15% RARS, 46% RCMD-RS, 15% RCMD, 15% RAEB-1 and 8% del (5q), is not found persuasive because MPEP 2123 [R-5] II states: disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).
2. Attie ‘286 teach the disclosure provides methods for treating or preventing myelodysplastic syndrome (MDS) and/or one or more complications of MDS, comprising administering to a subject in need thereof an effective amount of an ActRII antagonist, wherein the subject has bone marrow cells that test positive for one or more mutations in a gene selected from the group consisting of: SF3B1, DNMT3A, and TET2. Optionally the subject has previously been treated with one or more EPO receptor agonists. Optionally the subject has an inadequate response to the EPO receptor agonist. Optionally the subject is no longer responsive to the EPO receptor agonist. Optionally the EPO receptor agonist is EPO. Optionally the subject has a subtype of MDS selected from: MDS with refractory anemia with ring sideroblasts (RARS); MDS with refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) (see paragraph 0017).
Attie '286 teach RARS-T has ring sideroblasts ≥15% erythroid precursors, no blasts in peripheral blood and <5% in the bone marrow, and thrombocytosis with a platelet count ≥450x10⁹/L (para 0099).
The Examiner maintains that Attie ‘286 teach the claimed patient population, as recited in amended claim 1.
In addition, the Examiner notes that “MDS with RARS-T” to means “Myelodysplastic Syndrome with Refractory Anemia with Ring Sideroblasts and Thrombocytosis. The Examiner notes that refractory anemia is defined as an anemia that does not respond to standard treatments, making it "refractory" or “resistant”.
Lastly, Attie ‘286 teach subcutaneous administered about of luspatercept of about 1.0 to about 1.75 mg/kg (para 04510).
Attie ‘280 teach ActRIl signaling inhibitors such as ACE-536 (also known as luspatercept). Attie ‘280 et teach luspatercept can be formulated at a concentration of 50 mg/ml, 10mM citrate sucrose and 0.02% polysorbate 80 at a pH of 6.5 (paras 33, 220- 224, 315-316, 328 and 349). Attie ‘280 teach pharmaceutical compositions in a single dosage pharmaceutical formulations comprising luspatercept wherein 37.5 mg of luspatercept is in a 3 ml glass vial package that has been reconstituted from a sterile preservative-free lyophilized cake or powder form with 0.68 ml water for injection. Attie ‘280 teach pharmaceutical compositions in a single dosage pharmaceutical formulations comprising luspatercept wherein 87.5 mg of luspatercept is in a 3 ml glass vial package that has been reconstituted from a sterile preservative-free lyophilized cake or powder form with 1.6 ml water for injection.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
Claims 1, 3-9, 12, 19, 24, 29-31 remain rejected under 35 U.S.C. 103 as being obvious over Attie et al. (US 2016/0289286; Attie ‘286) in view of Attie et al. (WO 2016/183280; published 17 November 2016; Attie ‘280) and Sibon et al. (ABSTRACT. Blood, (NOV 19 2010) Vol. 116, No. 21, pp. 1632).
The basis for this rejection is set forth at pages 11-15 of the previous Office Action (28 July 2025).
APPLICANT’S ARGUMENTS: Applicant states that claim 1 on which claim 30
depends, is amended to recite that the subject is refractory to, intolerant to, or ineligible for erythropoiesis-stimulating agent (ESA) treatment. Applicant maintains that this is not obvious in view of either Attie ‘286 or Atiie ‘280 as discussed above. Applicant argues that Sibon does not remedy this deficiency. Applicant argues that Sibon, like Attie '286, only describes patients with "RA (n=3), RAEB-1 (n=2), RARS (n=11), RCMD (n=12), and RCMD-RS." Applicant directs the Examiner’s attention to line 15-16 of "AB" in Sibon. Applicant argues that none of the patients in Sibon have RARS-T or a baseline platelet count higher than 400 x10⁹/L. Applicant maintains that for at least this reason, claim 1, and therefore claims 3-9, 12, 19, 24, and 29-31 depending on claim 1, are not obvious over Attie '286, Attie '280, and/or Sibon, whether these references are taken alone or in any combination.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The Attie '286 reference already teaches the claimed patient population. The Examiner has discussed above how Attie '286 teaches the patient population recited in amended claim 1. Specifically, Attie et al. teach experiments to examine the effects of luspatercept on anemia in patients with low or Int-risk MDS patients who are nonresponsive/refractory to ESAs (para 0451). In addition, Attie '286 teach that the luspatercept treatment decreases blood cell transfusion requirement by 100% (paragraphs 0017 and 0019)(applies to claim 5).
2. The Sibon reference teaches erythropoiesis-stimulating agents (ESAs) can correct anemia, but not all patients respond. Sibon teaches that the median response duration to ESAs is about 2 years. Based on Sibon’s teachings, it would be obvious that the subject receives an initial diagnosis of MDS between 2 to 5 years prior to administering luspatercept. This would include a window of time comprising an initial diagnosis of MDS, 2 years of treatment with an ESA to see if it is effective for correcting anemia, if it is not effective after 2 years of ESA treatment, administering luspatercept.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
Claims 1, 3, 6-9, 12, 24, 29 and 32 remain rejected under 35 U.S.C. 103 as being unpatentable over Platzbecker et al. (The Lancet Oncology. Volume 18, Issue 10, pages 1338-1347; submitted online September 1, 2017) in view of Wang et al. (Leukemia Vol. 20:1641- 1644; 2006) and Attie et al. (WO 2016/183280; published 17 November 2016; Attie ‘280).
The basis for this rejection is set forth at pages 7-9 of the previous Office Action (28 July 2025).
APPLICANT’S ARGUMENTS: Applicant argues that as stated above, claim 1 is amended herein to recite the subject is refractory to, intolerant to, or ineligible for erythropoiesis-stimulating. agent (ESA) treatment. Applicant argues that Platzbecker does not discuss subjects that both "had been previously treated with or were ineligible for any other therapeutic agent" and had "a baseline platelet count higher than 400 X 10⁹/L." Applicant argues that Attie '280 does not remedy this deficit. Applicant argues that Wang also does not remedy the deficiency of Platzbecker and Attie '280.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons.
1. Platzbecker et al. teach subjects who are refractory to prior erythropoiesis stimulating agents (ESA) treatment, intolerant to prior ESA treatment or ineligible for ESA treatment (please see Table 1, pages 1341 and page 1345, right column, last paragraph-page 13460.
Platzbecker et al. teach subcutaneously administering luspatercept for the treatment of anemia in subjects with low or intermediate 1 risk myelodysplastic syndromes (MDS). Platzbecker et al. teach that the subjects have the presence of at least 15% or more ring sideroblasts (abstract). Platzbecker et al. teach that response to luspatercept treatment was more frequent and more robust in patients with ring sideroblasts 15% or higher or SF3Bl mutations (Discussion, page 1346).
Wang et al. teach MDS patients with low or intermediate 1 risk myelodysplastic syndromes have a platelet count greater than 400 x 10°/L at the time of presentation or during the early phase of the disease (i.e., baseline)(page 1641, Tables 1 and 2).
2. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Examiner maintains that the combination of Platzbecker et al. and Wang et al. teach the patient population recited in amended claim 1.
3. Attie ‘280 teach ActRIl signaling inhibitors such as ACE-536 (also known as luspatercept). Attie ‘280 et teach luspatercept can be formulated at a concentration of 50 mg/ml, 10mM citrate sucrose and 0.02% polysorbate 80 at a pH of 6.5 (paras 33, 220- 224, 315-316, 328 and 349). Attie ‘280 teach pharmaceutical compositions in a single dosage pharmaceutical formulations comprising luspatercept wherein 37.5 mg of luspatercept is in a 3 ml glass vial package that has been reconstituted from a sterile preservative-free lyophilized cake or powder form with 0.68 ml water for injection. Attie ‘280 teach pharmaceutical compositions in a single dosage pharmaceutical formulations comprising luspatercept wherein 87.5 mg of luspatercept is in a 3 ml glass vial package that has been reconstituted from a sterile preservative-free lyophilized cake or powder form with 1.6 ml water for injection.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
Claims 1 and 30 remain rejected under 35 U.S.C. 103 as being unpatentable over Platzbecker et al. (The Lancet Oncology. Volume 18, Issue 10, pages 1338-1347; submitted online September 1, 2017) in view of Wang et al. (Leukemia Vol. 20:1641- 1644; 2006) and Attie et al. (WO 2016/183280; published 17 November 2016, Attie ‘280), as applied to claim 1 above, and further in view of Sibon et al. (ABSTRACT. Blood, (NOV 19 2010) Vol. 116, No. 21, pp. 1632).
The basis for this rejection is set forth at pages 9-11 of the previous Office Action (28 July 2025).
APPLICANT’S ARGUMENTS: Applicant argues that claim 1 is amended herein to recite that the subject is refractory to, intolerant to, or ineligible for erythropoiesis-stimulating agent (ESA) treatment," which is not obvious in view of any of Platzbecker, Wang, and Attie '280 as stated above. Applicant maintains that although Sibon et al. teach that erythropoiesis-stimulating agents (ESAs) can frequently correct anemia, but not all patients respond. Applicant argues that Sibon, like Attie '286, only describes patients with "RA (n=3), RAEB-1 (n=2), RARS (n=11), RCMD (n=12), and RCMD-RS." Applicant argues that none of the patients in Sibon have a platelet count of higher than 400 X 10⁹/L (or "RARS-T").
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons.
1. The combination of Platzbecker et al. and Wang et al. already teaches the claimed patient population. The Examiner has discussed above how the combination of Platzbecker and teaches the patient population recited in amended claim 1.
2. The Sibon reference teaches erythropoiesis-stimulating agents (ESAs) can correct anemia, but not all patients respond. Sibon teaches that the median response duration to ESAs is about 2 years. Based on Sibon’s teachings, it would be obvious that the subject receives an initial diagnosis of MDS between 2 to 5 years prior to administering luspatercept. This would include a window of time comprising an initial diagnosis of MDS, 2 years of treatment with an ESA to see if it is effective for correcting anemia, if it is not effective after 2 years of ESA treatment, administering luspatercept.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
APPLICANT’S ARGUMENTS Regarding Unexpected Results: Applicant argues that evidence of unobvious or unexpected advantageous properties, such as superiority in a property the claimed compound shares with the prior art, can rebut prima facie obviousness. "Evidence that a compound is unexpectedly superior in one of a spectrum of common properties. can be enough to rebut a prima facie case of obviousness." No set number of examples of superiority is required. See, In re Chupp, 816 F.2d 643, 646, 2 USPQ2d 1437, 1439 (Fed. Cir. 1987). See also Ex parte A, 17 USPQ2d 1716 (Bd. Pat. Appage & Inter. 1990) and M.P.E.P. § 716.02(a).
Applicant argues that the method of claim 1 is demonstrated in the specification as resulting in unexpected results in a subset of MDS patients, in particular, the subset of MDS patients having a baseline platelet count of higher than 400 X 10⁹/L. This improved efficacy in this patient subpopulation is not stated, nor could it have been predicted, based on the references cited in the Office Action.
Applicant’s arguments have been fully considered but are not found persuasive because the results discussed by Applicant are not unexpected in view of the prior art references cited above.
NEW CLAIM REJECTIONS/OBJECTIONS
Claim Rejections-35 USC § 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph
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.
Claim 5 is 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 5 is indefinite because of the recitation “RBC transfusion-dependent”. The instant specification teaches “HTB” refers to “high transfusion burden” (para 0063) and “LTB” as “low transfusion burden” (para 0067). The instant specification does not actually teach the limitation “RBC transfusion-dependent” or how the limitation “RBC transfusion-dependent” relates to HTB and LTB. For example, the specification does not teach if the limitation “RBC transfusion-dependent” includes only “high transfusion burden” or if it includes both “high transfusion burden” and “low transfusion burden”.
The limitation “RBC transfusion-dependent” is not defined by the specification, does not provide a standard for ascertaining the requisite degree and thus one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The metes and bounds of this claim cannot be determined.
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Written description, New Matter
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.
Claim 5 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter Rejection
The specification as originally filed does not provide support for the invention as now claimed:
“..wherein the subject is RBC transfusion-dependent..” (claim 5).
Applicant's amendment, filed 27 October 2025, asserts that no new matter has been added and states that claim 5 is amended for purpose of clarity. Applicant does not provide direction for the written description for the above-mentioned “limitations”.
Claim 5 is amended from “wherein the subject is a subject requiring RBC transfusion” to “wherein the subject is RBC transfusion-dependent”.
The Examiner cannot find a teaching of “RBC transfusion-dependent” in the instant specification.
The instant specification teaches “HTB” refers to high transfusion burden (para 0063) and “LTB” as low transfusion burden (para 0067).
Amended claim 5 results in New Matter because the instant specification does not teach the limitation “RBC transfusion-dependent” and what is encompassed by the limitation “RBC transfusion-dependent” as it relates to HTB, LTB or any other type of transfusion burden.
The specification as filed does not provide a written description or set forth the metes and bounds of this "limitations". The instant claims now recite limitations which were not disclosed in the specification as filed, and now change the scope of the instant disclosure as-filed.
Applicant is required to cancel the new matter in the response to this Office action. Alternatively, Applicant is invited to provide specific written support for the “limitations” indicated above or rely upon the limitations set forth in the specification as filed.
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 REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
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, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/R.M.D/Examiner, Art Unit 1647
1/27/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647