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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/06/2026 has been entered.
Status of Claims
Claims 1, 3-4, 32, 34, 37, 40-43 are amended. Claims 1-4, 28, 32, 34, 37, 40-43 are currently pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The claims have an earliest effective filing date of 09/13/2021, corresponding to application PRO 63/243,564.
Response to Remarks 05/06/2026
Applicant remarks regarding the 35 USC 112a rejection of claims 1-4, 28, 32, 34, 37, and 40-43 have been fully considered and are not persuasive. Applicant states: “In this regard, Applicant submits that the Office's allegation amounts to an indication that page 48, lines 16-20 fails for an unstated reason to evidence possession of the subject matter at issue. But the written description inquiry forbids conclusory statements (see, e.g., M.P.E.P. §706.03 (2024) ("Where a rejection not based on prior art is proper (lack of adequate written description, enablement, or utility, etc.) such rejection should be stated with a full development of the reasons rather than by a mere conclusion.") (emphasis added)). In any event, Applicant's specification is replete with disclosure of the subject at issue. For the convenience of the Office, Applicant has set forth below the disclosure at page 48, lines 16-20 of such specification: In any of the embodiments described herein, for subjects that carry a loss-of- function variant for TET2 (such as, for example, due to the presence of an INDEL; a TET2 somatic mutation deficiency), the methods of treatment and prevention can exclude treatment with a PARP1 inhibitor. Such subjects can be otherwise treated as described herein.”
Applicant additionally states: “In any of the embodiments described herein, for subjects that are determined to have an increased risk of developing CHIP, such subjects that also carry a loss- of-function variant for TET2 (such as, for example, due to the presence of an INDEL; a TET2 somatic mutation deficiency) can undergo a treatment or prevention regimen that excludes treatment with a PARP 1 inhibitor. Such subjects can be otherwise treated as described herein. Accordingly, subjects having a loss-of-function variant for TET2 and who have been determined to have an increased risk of developing CHIP can be excluded from the population of subjects amenable for treatment with a PARP1 inhibitor.”
Although the specification has adequate written description for excluding subjects having a loss-of-function variant for TET2 from treatment with a PARP1 inhibitor, the specification does not provide adequate written description for excluding subjects who DO NOT have a loss-of-function variant for TET2 as claimed in claim 1 of the instant application.
With respect to the rejection of claims 32, 34, 37, and 40-43 under 35 USC 112(a), Applicant states: “Claim 32 is NOT "claiming a broad genus of molecules". Rather, claim 32 recites (in relevant part):wherein when the CHIP comprises a myeloid neoplasia, the therapeutic agent that treats CHIP comprises arsenic trioxide, azacitidine, daunorubicin hydrochloride, cyclophosphamide, cytarabine, a combination of daunorubicin hydrochloride and a plurality of cytarabine liposomes, glasdegib maleate, dexamethasone, doxorubicin hydrochloride, enasidenib mesylate, gemtuzumab ozogamicin, gilteritinib fumarate, idarubicin hydrochloride, ivosidenib, midostaurin, mitoxantrone hydrochloride, azacitidine, prednisone, thioguanine, venetoclax, or vincristine sulfate; wherein when the CHIP comprises a lymphoid neoplasia, the therapeutic agent that treats CHIP comprises acalabrutinib, alemtuzumab, ofatumumab, bendamustine hydrochloride, chlorambucil, duvelisib, cyclophosphamide, dexamethasone, fludarabine phosphate, obinutuzumab, ibrutinib, prednisone, rituximab, a combination of rituximab and hyaluronidase human, venetoclax, or idelalisib; wherein when the CHIP comprises a coronary heart disease, the therapeutic agent that treats CHIP comprises benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination of bisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprolol succinate, nadolol, pindolol, propranolol, solotol, timolol, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, metformin, or nitroglycerin; wherein when the CHIP comprises a myocardial infarction, the therapeutic agent that treats CHIP comprises aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole, integrilin, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination ofbisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprololsuccinate, nadolol, pindolol, propranolol, solotol, timolol, hydralazine ,minoxidil, streptokinase, reteplase, alteplase, urokinase, or tenecteplase; wherein when the CHIP comprises severe calcified aortic valve stenosis, the therapeutic agent that treats CHIP comprises benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination of bisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprolol succinate, nadolol, pindolol, propranolol, solotol, timolol, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone, bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, eplerenone, spironolactone, triamterene, amiodarone, flecainide, ibutilide, lidocaine, procainamide, propafenone, quinidine, or tocainide; Claim 32 could not recite better written description for the specific therapeutic agents recited therein.”
These arguments have been fully considered and are deemed persuasive. As such the rejection of claims 32, 34, 37, and 40-43 under 35 USC 112(a) has been withdrawn.
Applicant’s arguments and amendments regarding the 35 USC 103 rejection have been fully considered and are persuasive. Specifically, amending the claim to recite wherein the subject is not administered a PARP1 inhibitor overcomes the rejection. Therefore, the 35 USC 103 rejection is withdrawn.
New Rejections Necessitated by Amendment
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.
Claim(s) 1-4, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Kahn et al (WO2017156416, published: 09/14/2017) in view of Bressan et al (Bressan et al, Cancer Research, 2017, 77, 13; published 07/01/2017).
Kahn et al teach a method of treating CHIP or a therapy related neoplasm in a subject, the method comprising administering an inhibitor to a subject identified as having or having a propensity to develop CHIP or a therapy related neoplasm (Kahn et al, pg. 50-51, claim 10).
Therefore, Kahn et al teach a method of treating CHIP in a subject comprising administering an inhibitor to the subject. Kahn et al do not teach a method of treating CHIP in a subject comprising administering a Ly75 inhibitor to the subject. This deficiency is remedied by Bressen et al.
Bressen et al teaches use of a Ly75 inhibitor in different cancers including those derived from hematopoietic origins.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Kahn et al with those of Bressen et al to arrive a method of treating CHIP in a subject comprising administering a Ly75 inhibitor to the subject. One of ordinary skill in the art would have been motivated to do so, because Kahn et al teach a method of treating CHIP in a subject comprising administering an inhibitor to the subject. Furthermore based upon the teachings of Bressen et al, one of ordinary skill in the art would have been motivated to treat a disease of hematopoietic origins, such as in CHIP. As such one of ordinary skill in the art would have been motivated to modify the invention of Kahn et al, which teaches a method of treating CHIP in a subject comprising administering an inhibitor to the subject, to further include a using a Ly75 inhibitor because there would have been a reasonable expectation that the resultant invention, which comprises the administration of a Ly75 inhibitor to treat CHIP, is effective in treating CHIP. The invention of Kahn et al and Bressen et al meets the limitations of claim 1.
Regarding claim 2, Kahn et al teach the method can be used for a subject at risk of developing a hematologic cancer (Kahn et al, pg. 23, paragraph 5).
Regarding claims 3-4, Kahn et al teach that the inhibitor can be an siRNA (Kahn et al, pg. 30 paragraph 4- pg. 31, paragraph 1).
Regarding claim 28 Kahn et al teach the method where the subject receives the standard dosage or less (Kahn et al, pg. 28, paragraph 2, last two sentences).
Therefore the claims as a whole were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Rejections Maintained- Final 03/06/2026
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.
Claims 1-4, 28, 32, 34, 37, 40-43 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 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.
Claim 1 recites a method of treating clonal hematopoiesis of indeterminate potential (CHIP) in a subject, the method comprising administering a Lymphocyte Antigen 75 (LY75) inhibitor, a Cluster of Differentiation 164 (CD164) inhibitor, or a Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor, or any combination thereof, to the subject, wherein the subject does not carry a loss-of-function variant for Tet Methylcytosine Dioxygenase 2 (TET2).
Claim 32 recites a method of treating a subject with a therapeutic agent that prevents or reduces development of CHIP, treats clonal hematopoiesis of indeterminate potential (CHIP), wherein the subject has CHIP or is at risk of developing CHIP, the method comprising the steps of: determining whether the subject has an LY75 variant nucleic acid molecule, a CD 164 variant nucleic acid molecule, and/or a PARP1 variant nucleic acid molecule by: obtaining or having obtained a biological sample from the subject; and performing or having performed a sequence analysis on the biological sample to determine if the subject has a genotype comprising the LY75 variant nucleic acid molecule, the CD 164 variant nucleic acid molecule, and/or the PARP1 variant nucleic acid molecule; and administering or continuing to administer the therapeutic agent that prevents or reduces development of treats CHIP in a standard dosage amount to a subject that is LY75 reference, CD 164 reference, and/or PARP1 reference; and/or administering an LY75 inhibitor, a CD164 inhibitor, or a PARP1 inhibitor, or any combination thereof, to the subject that is LY75 reference, CD164 reference, and/or PARP1 reference; or administering or continuing to administer the therapeutic agent that prevents or reduces development of treats CHIP in an amount that is the same as or less than a standard dosage amount to a subject that is heterozygous for the LY75 variant nucleic acid molecule, the CD164 variant nucleic acid molecule, and/or the PARP1 variant nucleic acid molecule; and/or administering an LY75 inhibitor, a CD 164 inhibitor, or a PARP1 inhibitor, or any combination thereof, to the subject that is heterozygous for the LY75 variant nucleic acid molecule, the CD 164 variant nucleic acid molecule, and/or the PARP1 variant nucleic acid molecule; or administering or continuing to administer the therapeutic agent that prevents or reduces development of treats CHIP in an amount that is the same as or less than a standard dosage amount to a subject that is homozygous for the LY75 variant nucleic acid molecule, the CD164 variant nucleic acid molecule, and/or the PARP1 variant nucleic acid molecule; wherein the presence of a genotype having the LY75 variant nucleic acid molecule, the CD 164 variant nucleic acid molecule, and/or the PARP1 variant nucleic acid molecule indicates the subject has a decreased risk of developing CHIP; wherein the subject does not carry a loss-of-function variant for Tet Methylcytosine Dioxygenase 2 (TET2); wherein when the CHIP comprises a myeloid neoplasia, the therapeutic agent that treats CHIP comprises arsenic trioxide, azacitidine, daunorubicin hydrochloride, cyclophosphamide, cytarabine, a combination of daunorubicin hydrochloride and a plurality of cytarabine liposomes, glasdegib maleate, dexamethasone, doxorubicin hydrochloride, enasidenib mesylate, gemtuzumab ozogamicin, gilteritinib fumarate, idarubicin hydrochloride, ivosidenib, midostaurin, mitoxantrone hydrochloride, azacitidine, prednisone, thioguanine, venetoclax, or vincristine sulfate;wherein when the CHIP comprises a lymphoid neoplasia, the therapeutic agent that treats CHIP comprises acalabrutinib, alemtuzumab, ofatumumab, bendamustine hydrochloride, chlorambucil, duvelisib, cyclophosphamide, dexamethasone, fludarabine phosphate, obinutuzumab, ibrutinib, prednisone, rituximab, a combination of rituximab and hyaluronidase human, venetoclax, or idelalisib;wherein when the CHIP comprises a coronary heart disease, the therapeutic agent that treats CHIP comprises benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination ofbisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprolol succinate, nadolol, pindolol, propranolol, solotol, timolol, amlodipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, metformin, or nitroglycerin:wherein when the CHIP comprises a myocardial infarction, the therapeutic agent that treats CHIP comprises aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole, integrilin, benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination ofbisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprolol succinate, nadolol, pindolol, propranolol, solotol, timolol, hydralazine, minoxidil, streptokinase, reteplase, alteplase, urokinase, or tenecteplase: and wherein when the CHIP comprises severe calcified aortic valve stenosis, the therapeutic agent that treats CHIP comprises benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, acebutolol, atenolol, betaxolol, bisoprolol, a combination ofbisoprolol and hydrochlorothiazide, metoprolol tartrate, metoprolol succinate, nadolol, pindolol, propranolol, solotol, timolol, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone, bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, eplerenone, spironolactone, triamterene, amiodarone, flecainide, ibutilide, lidocaine, procainamide, propafenone, quinidine, or tocainide.
While the specification provides adequate description for the treatment of subjects with TET2 mutant disease, the specification does not include support for treating a subject wherein the subject does not carry a loss-of function variant for TET2. Applicant asserts that support for the amended claims may be found at page 48 of the specification, lines 16-20; however after reviewing the specification, it does not appear that the specification, including the claims, as originally filed, provide adequate support for a method of treating a subject wherein the subject does not carry a loss-of function variant for TET2.
Applicant is advised that the instant new matter rejection may be obviated by pointing to other disclosures in the specification, including the claims, as originally filed, which are believed to provide the necessary written support for these new limitations.
This is a new matter rejection.
Conclusion
No claim is allowed.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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