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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The report on patentability of the IPEA and/or ISA has been considered by the examiner.
Claim Rejections - 35 USC § 112
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 1 and 2 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for removing excess α-globin in erythroid cells from a patient having beta thalassemia, does not reasonably provide enablement for removing excess α-globin in a genus of erythroid cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claimed invention broadly embraces removing excess α-globin in a genus of erythroid cells comprising administering an effective amount of miR-144 antagomir or a miR-451 antagomir or a combination thereof. The broadest reasonable interpretation (BRI) of the claimed method embraces any type of cell, e.g., in vitro, ex vivo, in vivo.
The art of record (e.g., Fang et al. Haematologica 2018 103,406-416, cited on an IDS) and the as-filed specification (pages 6-24) teach that miR-144 antagomir or miR-451 antagomir are well known in the prior art and can be delivered to a cell or a subject to inhibit their expression of their respective miRNAs. Fang (supra) teach that, ”.. miR-144/451 is a key protector of erythroblasts during pathological states associated with dramatically increased erythropoietic demand, including acute blood loss and hemolytic anemia (abstract).”
A skilled artisan would possess the knowledge that there are several types of thalassemia, including alpha and beta. Αlpha-thalassemia is the result of deficient or absent synthesis of alpha globin chains leading to excess beta globin. Βeta-thalassemia is the result or absent of synthesis of beta globin, leading to excess alpha chains. The claimed method embraces alpha and beta thalassemia. However, only beta-thalassemia would be enabled because patients with alpha thalassemia do not have excess alpha globin chains. See WO2019084402, cited on an IDS.
In addition, the prior art teaches that miR-144/451 has been studied in patients with thalassemia. See Svasti et al. (Ann Hematol 2010, 89:953-958) and Saki et al. (Cell Journal 17, 2016, pages 583-593). The prior art teaches that animals not having thalassemia do not have excess α-globin in erythroid cells. For example, Svasti (supra) teach up-regulation of miR-451 was observed during thalassemic erythroid differentiation in erythroid progenitors derived from thalassemic peripheral blood C34+ cells, whereas expression pattern of miR-451 in erythroid cells obtained from other extravascular hemolytic anemia showed no up-regulation of miR-451.
The specification provides working examples showing that animal models of beta-thalassemia had excess α-globin in erythroid cells. The prior art and the specification do not teach which wild-type animals or animals not having beta thalassemia have excess α-globin in erythroid cells. Thus, the claimed method is only enabled for removing excess α-globin in erythroid cells from an animal having beta-thalassemia.
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 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over UNIV YANGZHOU CN105854017 ((‘017), cited on an IDS, see English translation, pages 1-40) taken with Olson et al. (US 20140011859, cited on an IDS).
‘017 teaches a method of treating beta-thalassemia in a subject comprising providing a reagent to the subject, wherein the reagent reduces expression level of miR-144/451 genes or the amount of miR-144/451 (pages 7-17 and 35-39 of English translation). ‘017 provides antisense sequences for miR-144 and miR-451 (page 17). Claim 7 of ‘017 on pages 36-37 recite a method of treating beta-thalassemia using a reagent that reduces expression and/or function of the mature sequence of miR-144 and miR-451, wherein the reagent is shRNA, siRNA, RNAi, antisense sequence, LNA technology and CRISPR-Cas9.
‘017 does not specifically teach using an antisense oligonucleotide that is complementary to a miR-144 and/or miR-451 (also known as miR-144 antagomir or miR-451 antagomir) in the method.
However, antagomirs were well known to a person of ordinary skill in the art to reduce expression and/or function of a microRNA in a cell or a subject as taught by Olson (pages 1-11). Olson teaches using anti-mir 451 (also known as miR-451 antagomir) to treat a disorder (polycythemias) in a subject.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of ‘017 taken with Olson to use an antisense oligonucleotide that is complementary to miR-144 and/or miR-451 to treat beta-thalassemia in a subject in need thereof, namely to arrive at the claimed invention. Since reducing either microRNA can treat beta-thalassemia as taught by ‘017, one of ordinary skill in the art would have been motivated to combine the teaching as a simple substitution to treat beta thalassemia using miR-144 and/or miR-451 antagomirs to reduce expression of miR-144 and/or miR-451 in the subject. See MPEP 2143 A and B. With respect to the limitation ‘removing excess free α-globin in erythroid cells comprising contacting erythroid cells with an effective amount’ in the pre-amble of claim 1, the method made obvious by ’017 taken with Olson would inherently have this functional limitation or be a latent property of the method because ‘017 taken with Olson makes obvious the claimed method steps. In addition, the specification does not appear to provide a definition for the term ‘effective amount’. In view of the BRI, the amount reads on any amount that reduces expression and/or function of miR-144 or miR-451 reads on the term.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636