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 Claims
Claims 5-27, 29-31, 33, 35, 36, 38, 39, and 44-139 are cancelled. Claims 1, 3, 28, 32, 34, 37, 40, 42, and 43 are amended. Claims 1-4, 28, 32, 34, 37, 40-43 are pending and under examination.
Priority
Application claims priority to 63/243,564 filed 09/13/2021 and 63/271,171 filed 10/24/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/01/2023 has been considered.
Response to Remarks filed 11/20/20225
Applicant’s arguments and amendments regarding the 35 USC 101 rejection have been fully considered and are persuasive. Specifically, cancelling claim 139 remedies the rejection. Therefore the 35 USC 101 rejection is withdrawn.
Applicant’s arguments and amendments regarding the 35 USC 112a rejection have been fully considered and are not persuasive. Specifically, removing the preventing language from the claims remedies the enablement rejection. However, regarding the written description rejection, only 3 inhibitors are disclosed in the specification and Applicant claims a broad genus of therapeutic agents in claim 32. Therefore, the 35 USC 112 enablement rejection is withdrawn, and the 35 USC 112 written description rejection is maintained.
Applicant’s arguments and amendments regarding the 35 USC 103 rejection have been fully considered and are persuasive. Specifically, amending the claims to require the treatment of a subject that does not carry a loss-of-function variant for TET2 obviates the rejection.
New Rejections Necessitated by Amendment
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.
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 Wahab (Wahab, The Hematologist, 2017, vol 14, published 10/27/2017).
Kahn et al teach a method of treating or preventing 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 preventing or reducing the development of CHIP in a subject comprising administering an inhibitor to the subject. Kahn et al do not teach a method of preventing or reducing the development of CHIP in a subject comprising administering a PARP inhibitor to the subject. This deficiency is remedied by Jing et al.
Kahn et al do not teach the use of PARPi in TET2- competent (HSPCs). This deficiency is remedied by Wahab.
Wahab teaches that TET2 competent CHIP can be treated with PARPi (Wahab et al, Abstract).
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 Jing et al and Wahab to arrive a method of preventing or reducing the development of CHIP in a subject comprising administering a PARP 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 preventing or reducing the development of CHIP in a subject comprising administering an inhibitor to the subject. Furthermore based upon the teachings of Jing et al, one of ordinary skill in the art would have been motivated to treat a disease comprising TET2 mutant HSCs, such as in CHIP. Importantly, based upon the teachings of Wahab one of ordinary skill in the ART would have been motivated to treat TET2 competent CHIP because Wahab teaches that normal functioning TET2 makes HSCs more susceptible to PARPi. 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 preventing or reducing the development of CHIP in a subject comprising administering an inhibitor to the subject, to further include a using a PARP inhibitor because there would have been a reasonable expectation that the resultant invention, which comprises the administration of a PARP inhibitor to treat CHIP, is effective in treating CHIP. The invention of Kahn et al, Jing et al and Wahab meets the limitations of claims 1 and 139.
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 28Kahn 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- Nonfinal 08/21/2025
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 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 32, 34 and 37 are drawn to therapeutic agents that prevent or reduce development of CHIP.
Following a review of the specification, it appears that Applicant has disclosed CD164 inhibitors, PARP inhibitors, and LY75 inhibitors as therapeutic agents that prevent or reduce development of CHIP. However in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple therapeutic agents that prevent or reduce development of CHIP. Even though Applicant has disclosed three species within said genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed three species within the genus claimed. However given the substantial variation within the genus, the disclosure of three species comprised within the claimed genus is not adequate. The specification also fails to provide relevant, identifying characteristics of an agent that prevent or reduce development of CHIP.
Although screening techniques can be used to find therapeutic agents that prevent or reduce the development of CHIP, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Accordingly given the unpredictability associated with treating CHIP and given the lack of particularity with which the claimed therapeutic agents are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Conclusion
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.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642