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 .
Priority
The present application claims priority to the application, 63/479,955, with effective filing date of 13 January 2023, respectively.
Claim Status
This Office Action is in response to Applicant’s Response to Restriction Requirement filed, 26 May 2026.
Applicant's election with traverse of Group I (claims 1-7) in the reply filed on 26 May 2026 is acknowledged. While Applicant’s response did not explicitly indicate that the election was made with traverse, the Applicant submitted substantive arguments. Accordingly, the Examiner has treated the election with traverse.
The traversal is on the ground(s) that Group II increases O-linked N-acetylglucosaminase (OGA), which reduces O-GlcNAcylation (see e.g. claim 11 and [00026] of the specification).
Applicant’s remarks are acknowledged; however, the Examiner notes that the process of claim 1 (a method of treating HFpEF via administering an OGT inhibitor) uses a materially different product than the process of claim 8 (a method of treating HFpEF via administering a composition that increases OGA). J Liu (J. Molec. Cell. Cardiolog.¸2006, 40, 303-312) teaches that the administration of glucosamine increased cardiac O-GlcNAc (OGA) levels (page 311, column 1, paragraph 1). Accordingly, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Accordingly, the restriction is proper.
Claims 8-15 are withdrawn from further consideration pursuant to 37 CR 1.142(b) as being drawn to a nonelected group (Group II: claims 8-15), there being no allowable generic or linking claim.
Claims 1-7 are under consideration in the instant office action.
Information Disclosure Statement
The Information Disclosure Statements filed 8 August 2024 and the references cited therein have been considered, unless indicated otherwise.
Claim Interpretation
For clarity, the Examiner interprets “subject” to include non-human animals, as defined in the specification ([00023]).
Additionally, the Examiner notes that claim 1 specifies treating or preventing heart failure with preserved ejection fraction (HFpEF). The Examiner notes that Cilia (Am. J. Lifestyle Med.¸2017¸13(2), 182-189) teaches prevention of heart failure with preserved ejection fraction via controlling blood pressure with common pharmacological agents (small molecules/pharmaceuticals; page 185, column 3, paragraph 3). Additionally, Zeng (Am. J. Hypertension¸2025¸38, 964-973) teaches that loss of OGT decreased blood pressure and that OGT increases systemic blood pressure and fluid retention in patients with heart failure (page 969, column 1, paragraph 2).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
1. Claim(s) 1 and 4-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tatekoshi (Abstract P3014, Circulation research, 14 Nov 2022, 131 Suppl 1).
Tatekoshi teaches that endothelial cell dysfunction underlies the pathogenesis of heart failure with preserved ejection fraction (HFpEF; abstract). Tatekoshi teaches ST045849, an O-GlcNAc transferase (OGT) inhibitor, rescued the less angiogenic ability in the endothelial cells in the HFpEF mouse model (abstract).
Regarding claim 1, Tatekoshi teaches a method of treating HFpEF via administering the OGT inhibitor, ST045849 (abstract).
Regarding claim 4, Tatekoshi teaches a method of treating HFpEF via administering the OGT inhibitor, ST045849 (abstract). Additionally, as Applicant does not further specify a certain concentration dosage of the OGT inhibitor to reduce O-GlcNAcylation in endothelial cells of the heart, claim 4 does not specify an additional step but does specify an additional effect. Thus, claim 4 merely recites an additional effect of a claimed method. Further, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Consequently, Tatekoshi teaches the claimed method of treating HFpEF via STN045849, wherein the OGT inhibitor to reduce O-GlcNAcylation in endothelial cells of the heart.
Regarding claim 5, Tatekoshi teaches a method of treating HFpEF via administering the OGT inhibitor, ST045849 (abstract). Additionally, Tatekoshi teaches that O-GlcNAcylation in endothelial cells is mediated by hexokinase-1 (HK-1) dislocation from mitochondria in cells (abstract).
Regarding claim 6, Tatekoshi teaches a method of treating HFpEF via administering the OGT inhibitor, ST045849 (abstract). Additionally, as Applicant does not further specify a certain concentration dosage of the OGT inhibitor, wherein diastolic function is restored or maintained in the heart of the subject, claim 6 does not specify an additional step but does specify an additional effect. Thus, claim 6 merely recites an additional effect of a claimed method. Further, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Consequently, Tatekoshi teaches the claimed method of treating HFpEF via STN045849, wherein the OGT inhibitor, wherein diastolic function is restored or maintained in the heart of the subject.
Regarding claim 7, Tatekoshi teaches a method of treating HFpEF via administering the OGT inhibitor, ST045849 (abstract). Additionally, Tatekoshi teaches that ST045849 rescued angiogenic function in endothelial cells of the heart (abstract).
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.
2. Claim(s) 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (ACIE¸ 2018, 57, 7644-7648, see IDS filed 8/8/24) in view of Zouein (J. Cardiovasc. Pharmacol.¸2013, 62(1), 13-21).
Liu teaches OGT inhibitors to decrease O-GlcNAc (β-O-linked N-acetylglucosamine) levels in vivo (abstract; page 7645, column 1, paragraph 1). Liu teaches that O-GlcNAc levels have been implicated in various diseases including cancer, neurodegeneration, cardiovascular disease, and obesity (page 7644, column 2, paragraph 2). Liu teaches that OGT (O-GlcNAc transferase) catalyzes the attachment of GlcNAc to hydroxy groups of serine/threonine residues in target proteins and that OGA (O-GlcNAcase) cleaves O-GlcNAc from proteins (page 7644, column 1, paragraph 1; page 7644, column 2, paragraph 1). Liu teaches that studies on the influence of decreased O-GlcNAc on mammalian physiology are lacking as there are no OGT inhibitors suitable for use in vivo (page 7645, column 1, paragraph 1). Liu teaches that previous efforts using broad-spectrum amidotransferase inhibitors (e.g. DON) promiscuously blocked all amidotransferases that biosynthesize many cellular metabolites including UDP-GlcNAc (age 7645, column 1, paragraph 2). Additionally, Liu teaches high throughput leads based upon DON showed modest cellular activity, limited solubility, and off-target cellular toxicity (page 7645, column 1, paragraph 2). Liu teaches that other compounds, such as 5SGlcNAc, could diffuse across the plasma membrane and was a competitive OGT inhibitor and non-toxic, but suffered from poor solubility in aqueous solution (page 7645, column 1, paragraph 2). Liu then teaches water-soluble analogs of 5SGlcNAc, such as Compound 12, which is 5SGlcNHex (page 7645, column 2, paragraph 2; page 7645, Figure 2). Liu teaches administration of 3-300 mg/kg in mice via intraperitoneal delivery of Compound 12 (page 7646, column 1, paragraph 2; page 7646, column 2, paragraph 1; Figures S5). Liu teaches that OGlcNAc levels were reduced in the kidneys, lungs, fat, pancreas, heart, spleen, and muscle tissue but no in the blood or brain (page 7646, column 2, paragraph 1). Due to issues of mice being moribund, Liu teaches that the mice were dosed with lower doses of Compound 12 and still found reduced OGlcNAc levels in various tissues 16h after dosing but no effects on the brain, liver, pancreas, and kidney (page 7646, column 2, paragraph 1).
Regarding claim 1, Liu fails to teach treating heart failure with preserved ejection fraction (HFpEF).
Zouein teaches that approximately half of heart failure patients have a normal ejection fraction, which is known as heart failure with preserved ejection fraction (HFpEF; abstract). Zouein teaches that this heart failure subtype is commonly associated with other cardiovascular comorbidities, such as hypertension and diabetes (abstract). Zouein teaches that HFpEF is increasing at a steady rate and is predicted to become the leading cause of heart failure within a decade (abstract). Zouein teaches that HFpEF is characterized by impaired diastolic function (abstract; page 13, column 2, paragraph 1). Zouein also teaches the need for new treatments of HFpEF as there are no evidenced-based therapies for HFpEF (page 16, column 1, bullet point 2; page 19, column 1, paragraph 3), but Zouein teaches that there are several drugs under evaluation for HFpEF (page 16, column 2, paragraph 2). Zouein teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules (page 19, column 1, paragraph 3).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to modify the method of reducing O-GlcNAc via Compound 12 of Liu with the method of treating HFpEF of Zouein as O-GlcNAc levels have been implicated in HFpEF comorbidities. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Liu teaches OGT inhibitors to decrease O-GlcNAc (β-O-linked N-acetylglucosamine) levels in vivo,
-Liu teaches that O-GlcNAc levels have been implicated in various diseases including cancer, neurodegeneration, cardiovascular disease, and obesity,
-Liu teaches that OGT (O-GlcNAc transferase) catalyzes the attachment of GlcNAc to hydroxy groups of serine/threonine residues in target proteins and that OGA (O-GlcNAcase) cleaves O-GlcNAc from proteins,
-Liu teaches that studies on the influence of decreased O-GlcNAc on mammalian physiology are lacking as there are no OGT inhibitors suitable for use in vivo,
-Liu teaches that previous efforts using broad-spectrum amidotransferase inhibitors (e.g. DON) promiscuously blocked all amidotransferases that biosynthesize many cellular metabolites including UDP-GlcNAc,
-Liu teaches high throughput leads based upon DON showed modest cellular activity, limited solubility, and off-target cellular toxicity,
-Liu teaches that other compounds, such as 5SGlcNAc, could diffuse across the plasma membrane and was a competitive OGT inhibitor and non-toxic, but suffered from poor solubility in aqueous solution,
-Liu then teaches water-soluble analogs of 5SGlcNAc, such as Compound 12, which is 5SGlcNHex,
-Liu teaches administration of 3-300 mg/kg in mice via intraperitoneal delivery of Compound 12,
-Liu teaches that OGlcNAc levels were reduced in the kidneys, lungs, fat, pancreas, heart, spleen, and muscle tissue but no in the blood or brain,
-Due to issues of mice being moribund, Liu teaches that the mice were dosed with lower doses of Compound 12 and still found reduced OGlcNAc levels in various tissues 16h after dosing but no effects on the brain, liver, pancreas, and kidney,
-Zouein teaches that approximately half of heart failure patients have a normal ejection fraction, which is known as heart failure with preserved ejection fraction (HFpEF)
-Zouein teaches that this heart failure subtype is commonly associated with other cardiovascular comorbidities, such as hypertension and diabetes,
-Zouein teaches that HFpEF is increasing at a steady rate and is predicted to become the leading cause of heart failure within a decade,
-Zouein teaches that HFpEF is characterized by impaired diastolic function,
-Zouein also teaches the need for new treatments of HFpEF as there are no evidenced-based therapies for HFpEF, but Zouein teaches that there are several drugs under evaluation for HFpEF, and
-Zouein that teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules.
Accordingly, the combination of Liu and Zouein teaches a method of treating HFpEF via the OGT inhibitor, 5SGlcNHex.
Regarding claim 2, Liu teaches the OGT inhibitor, 5SGlcNHex (page 7645, column 1, paragraph 2; page 7645, column 2, paragraph 2; page 7645, Figure 2).
Regarding claim 3, Liu teaches a composition of 5SGlcNHex, which is administered at 3-300 mg/kg to a mouse via intraperitoneal delivery (page 7646, column 1, paragraph 2; page 7646, column 2, paragraph 1; Figures S5). Zouein teaches that there are several drugs (pharmaceutical compositions) under evaluation for HFpEF (page 16, column 2, paragraph 2), but Zouein teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules (page 19, column 1, paragraph 3). Thus, the combination of Liu and Zouein teaches a pharmaceutical composition that is administered to a subject with or at risk of experiencing HFpEF.
Regarding claim 4, Liu teaches the OGT inhibitor, 5SGlcNHex, which reduces protein O-GlcNAcylation (page 7645, column 1, paragraph 2; page 7645, column 2, paragraph 2; page 7645, Figure 2).
Regarding claim 5, Liu teaches the OGT inhibitor, 5SGlcNHex, which reduces protein O-GlcNAcylation (page 7645, column 1, paragraph 2; page 7645, column 2, paragraph 2; page 7645, Figure 2). Zouein teaches that there are several drugs (pharmaceutical compositions) under evaluation for HFpEF (page 16, column 2, paragraph 2), but Zouein teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules (page 19, column 1, paragraph 3). Additionally, as Applicant does not further specify a certain concentration dosage of 5SGlcNHex reducing protein O-GlcNAcylation in endothelial cells, which is mediated by hexokinase-1 (HK-1) dislocation from mitochondria in the cells, claim 5 does not specify an additional step but does specify an additional effect. Thus, claim 5 merely recites an additional effect of a claimed method. Further, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Consequently, the combination of Liu and Zouein teaches the claimed method of treating HFpEF via 5SGlcNHex, wherein the protein O-GlcNAcylation in the endothelial cells is mediated by hexokinase-1 dislocation from mitochondria in the cells.
Regarding claim 6, Liu teaches the OGT inhibitor, 5SGlcNHex, which reduces protein O-GlcNAcylation (page 7645, column 1, paragraph 2; page 7645, column 2, paragraph 2; page 7645, Figure 2). Zouein teaches that there are several drugs (pharmaceutical compositions) under evaluation for HFpEF (page 16, column 2, paragraph 2), but Zouein teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules (page 19, column 1, paragraph 3). Additionally, as Applicant does not further specify a certain concentration dosage for diastolic function restoration or maintenance in the heart of the subject, claim 6 does not specify an additional step but does specify an additional effect. Thus, claim 6 merely recites an additional effect of a claimed method. Further, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Consequently, the combination of Liu and Zouein teaches the claimed method of treating HFpEF via 5SGlcNHex, wherein diastolic function is restored or maintained in the heart of the subject.
Regarding claim 7, Liu teaches the OGT inhibitor, 5SGlcNHex, which reduces protein O-GlcNAcylation (page 7645, column 1, paragraph 2; page 7645, column 2, paragraph 2; page 7645, Figure 2). Zouein teaches that there are several drugs (pharmaceutical compositions) under evaluation for HFpEF (page 16, column 2, paragraph 2), but Zouein teaches that failure of trials thus far to demonstrate any benefit of drugs that have proven so effective in treating HFrEF supports a need for novel drug approaches to HFpEF and thus suggests treating HFpEF via small molecules (page 19, column 1, paragraph 3). Additionally, as Applicant does not further specify a certain concentration dosage wherein the OGT inhibitor restores or maintains angiogenic function in endothelial cells of the heart, claim 7 does not specify an additional step but does specify an additional effect. Thus, claim 7 merely recites an additional effect of a claimed method. Further, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the Examiner may make a rejection under both 35 U.S.C. 102 and 103. This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. See MPEP § 2112(II) and (III). Consequently, the combination of Liu and Zouein teaches the claimed method of treating HFpEF via 5SGlcNHex, wherein the OGT inhibitor restores or maintains angiogenic function in endothelial cells of the heart.
Conclusion
No claim is allowed.
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/MADELINE M. DEKARSKE/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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