Detailed Action
The present office action is in response to the amendments filed on 21 Aug 2025.
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
Claims 1, 6, 10, 14, 26-29, 33, 37, 39-40 of the pending application have been examined on the merits. Claims 2-3, 17-18, 20, 22, 24 remain withdrawn. Acknowledgement is made of the amendments filed 21 Aug 2025. Acknowledgement is made of the cancellation of claims 4-5, 7-9, 11-13, 15-16, 19, 21, 23, 25, 30-32, 34-36, and 38.
Priority
Applicants identify the instant application, Serial #: 17/763,445, filed 24 Mar 2022, as a National Stage Entry of International Patent Application #: PCT/US2020/052842, filed 25 Sep 2020, which claims priority from U.S. Provisional Application #: 62/907087, filed 27 Sep 2019.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 21 Aug 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Arguments
Acknowledgement is made of the amendments filed 21 Aug 2025.
The rejection of claims 1, 10, and 14 under 35 U.S.C. § 112(a) is rendered moot following applicant amendments.
The rejection of claim 5 under 35 U.S.C. § 103 is rendered moot following applicant amendments.
Regarding the rejection of claims 1, 6, 10, 14, 26-29, 33, 37, and 39-40 under 35 U.S.C. § 103 over Silva (São Paulo State University, 2018, Master's Dissertation; provided in the office action mailed 22 May 2025), hereinafter Silva, further in view of Lamonica et al. (PNAS, 2011, 108:E159-E168; provided in the office action mailed 22 May 2025), hereinafter Lamonica, and Ware et al. (Lancet, 2017, 390:311-323; provided in the office action mailed 22 May 2025), hereinafter Ware, applicant's arguments filed 21 Aug 2025 have been fully considered but they are not persuasive.
Applicant argues that claims 1 and 26 recite the use of BET protein inhibitors to induce expression of fetal and embryonic hemoglobin levels, but that this limitation is not taught or suggested by Silva, Ware, or Lamonica (Applicant Reply, pg. 7). Applicant further argues that Silva, Ware, nor Lamonica teach the limitations of claim 39 where administration of a BET protein inhibitor induces expression of fetal and embryonic hemoglobin and decreases expression of adult hemoglobin in a subject (Applicant Reply, pgs. 7-8).
Applicant argues that the outcomes of the method taught by Silva, Ware, and Lamonica would not be the same as the outcomes of the method found in the instant claims. However, Silva, Ware, and Lamonica teach the same steps as the instant claims, of administering a BET protein inhibitor, JQ1, to treat HbSS. By having the same steps, the two methods must necessarily have the same outcomes. Inducing expression of fetal hemoglobin, inducing embryonic hemoglobin in a subject, alleviating symptoms of an inherited blood disorder, inducing erythropoiesis, and decreasing expression of adult hemoglobin in a subject are all outcomes of the method of treating HbSS in a subject by administering the BET protein inhibitor, JQ1, as found in the instant claims. Therefore, since the same steps necessarily lead to the same outcomes, the outcomes found in the instant claims must also be the outcomes of the method taught by Silva, Ware, and Lamonica.
In light of the discussion above, the rejection of claims 1, 6, 10, 14, 26-29, 33, 37, and 39-40 under 35 U.S.C. § 103, as made obvious over Silva, Ware, and Lamonica is maintained for the reasons of record and restated 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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) 1, 6, 10, 14, 26-29, 33, 37, 39-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Silva (São Paulo State University, 2018, Master's Dissertation; English translation included), hereinafter Silva, further in view of Lamonica et al. (PNAS, 2011, 108:E159-E168), hereinafter Lamonica, and Ware.
Silva teaches that HbF levels decrease due to decreased production of gamma-globin and that the inhibition of gamma-globin gene transcription is due to the binding of the repressor complex consisting of BCL11A, FOG1, and GATA-1 to the gamma-gamma globin gene locus located on chromosome 11 (pg. 16). Silva teaches that the capacity of compounds, such as resveratrol, to increase gamma-globin gene transcription and HbF production are related in part to the capacity to modulate the levels of GATA-1 and BCL11A (pg. 23). Silva also teaches that GATA-1 recruitment to the gamma-globin gene occurs through the action of bromodomains, specifically BRD3 binds to acetylated GATA-1 and that exposure of erythroid cells to BET-bromodomain inhibitors decreases GATA-1 occupancy and may regulate the transcription of a number of genes (pg. 23). Silva teaches that Compound IX obtained the highest BRD3 inhibition value of 80% at 100 µM (pg. 64 and pg. 49, Fig. 10). Silva also teaches that JQ1 inhibited BRD3 at close to 100% at 3 µM (pg. 49, Fig. 10). Silva teaches that Compound IX induced an increase in the levels of gamma-globin gene expression in K562 cells after 24 hours of exposure (pg. 64). However, Silva does not teach treating sickle cell anemia by increasing HbF through administration of JQ1.
Ware teaches that sickle cell disease is caused by the inheritance of abnormal beta-globin alleles carrying the sickle mutation and the most common and severe form is homozygous HbSS, also known as sickle cell anemia, which permits the formation of HbS (pg. 311, column 2). Ware teaches that HbF inhibits intracellular HbS polymerization and that since higher HbF is associated with reduced morbidity and mortality it is a logical goal to induce HbF to treat sickle cell anemia. Ware further teaches there is an unacceptable dearth of therapeutic options for sickle cell disease (pg. 316, column 2).
Lamonica teaches that pharmacologic inhibition of GATA-1's interaction with BRD3 reduce the association of both proteins at key erythroid genes (pg. E160, column 2). Lamonica further teaches using the pharmacologic compound GW841819X, which is extremely similar in structure and function to the compound JQ1, to inhibit binding between GATA-1 and BRD3 (pg. E164, column 2).
It would be obvious to a person of ordinary skill in the art that inhibiting BRD3 inhibits recruitment of GATA-1 to gamma globin gene locus as taught by Silva and Lamonica. It would further be obvious to the artisan that inhibition of GATA-1 recruitment to the gamma globin gene locus increases levels of gamma globin and further increases levels of fetal hemoglobin. The artisan would be motivated to administer a drug to inhibit BRD3 and increase gamma globin levels to produce HbF in the treatment of HbSS to help fill the dearth of therapeutic options for sickle cell disease as taught by Ware.
It would be obvious to a person having ordinary skill in the art to use JQ1 over Compound IX to inhibit BRD3. The artisan would be motivated to use JQ1 because JQ1 inhibits Brd3 close to 100% at a 3 µM dose whereas Compound IX does not fully inhibit BRD3 even at 100 µM as taught by Silva.
Thus, it would be obvious to the artisan that by treating a patient with HbSS by administering JQ1, the levels of fetal hemoglobin would rise, HbS polymerization would be inhibited, and HbSS would be treated.
The limitations of inducing expression of fetal hemoglobin in a subject (instant claims 1 and 26-27), inducing embryonic hemoglobin in a subject (instant claim 1, 26, and 28), the alleviating of symptoms of an inherited blood disorder (instant claim 37), and inducing erythropoiesis in a subject (instant claim 39) are the outcomes of steps performed in the administration of a BET protein inhibitor to a subject. Silva, Ware, and Lamonica make it obvious to the person having ordinary skill in the art to administer a BET protein inhibitor to treat HbSS and, therefore, must necessarily have the same outcomes as instant claims 1, 26-28, 37, and 39.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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