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 the Claims
Claims 1 – 18 are pending.
Claims 1 – 13, 16 and 18 and rejected.
Claims 14 – 15 and 17 are objected.
Response to Applicant’s Remarks
Applicant’s remarks filed on February 9, 2026 have been fully considered.
Regarding the objections to claims 13 – 16, Applicant did not amend the claims or provide any remarks to address the issues. Therefore, the objections are maintained.
Regarding the rejections:
35 U.S.C. 102(a)(1) of claims 1 – 4, 6 and 8 – 11 as being anticipated by Mia et al.,
35 U.S.C. 103 of claims 12 – 14 as being unpatentable over Mia et al., as applied to claims 1 – 4, 6 and 8 – 11 above, and
35 U.S.C. 103 of claims 7, 15 and 17 as being unpatentable over Mia et al., as applied to claims 1 – 4, 6 and 8 – 14 above, further in view of Tan et al.,
Applicant’s remarks and the Declaration under 37 C.F.R. 1.130(a) of Dr. Konstantinos Drosatos have been considered. Applicant state that the filing date of the instant application is less than one year after the publication of the Mia reference. Applicant rely on 35 U.S.C. 102(b)(1)(A) and 35 U.S.C. 102(b)(1)(A) exceptions to state that the Mia reference is a publication by the inventors, and is not available as prior art. Applicant’s remarks are persuasive and the rejections are withdrawn.
Regarding the rejections:
35 U.S.C. 102(a)(1) of claims 1 – 4 and 7 – 11 as being anticipated by Ziberna K. et al.,
35 U.S.C. 103 of claim 5 as being unpatentable over Ziberna K. et al., as applied to claims 1 – 4 and 7 – 11 above, further in view of Xintaropoulou et al., and
35 U.S.C. 103 of claims 6, 12 – 13 and 16 as being unpatentable over Ziberna et al., as applied to claims 1 – 5 and 7 – 11 above, further in view of Xintaropoulou et al.,
35 U.S.C. 103 of claim 18 as being unpatentable over Ziberna et al. in view of Xintaropoulou et al., as applied to claims 1 – 5 and 7 – 11 above,
Applicant’s remarks have been considered and addressed below:
On page 6, 3rd paragraph of the remarks, Applicant note Ziberna reference is merely an abstract from a presentation at the 2017 BCS Annual Conference. Applicant state that Ziberna disclose that the murine model overexpress mGCH1 did not develop left ventricle dysfunction, while the WT diabetic models did. Ziberna does not disclose that any Glut-1 inhibitor was used to treat diabetic cardiomyopathy. Thus, Applicant assert that Ziberna reference cannot anticipate claim 1 or any claim depending therefrom.
On page 6, 4th paragraph – page 7, 3rd paragraph, Applicant state that Ziberna reference, alone or in combination with any of the other cited references, does not render the claims unpatentable. Applicant cites a journal article (Carnicer, Ricardo et al., Circulation Research 128.5 (2021), 585-601) that corresponds to the information from the Ziberna presentation abstract, which reiterates the statement “all agents significantly inhibited glucose transport only in mGCH1-Tg and abolished the differences between genotypes”. Applicant note and further summarizes the teachings that Carnicer teaches away from the claimed methods and a person of ordinary skill in the art would not combine the cited references to arrive at the presently claimed methods because Ziberna is silent to the use of the inhibitor in treating diabetic cardiomyopathy and because subsequent teachings teach away from the use. Emphasis added. However, in response to Applicant’s arguments, MPEP §2131.05 states:
“ ‘Arguments that the alleged anticipatory prior art… ‘teaches away from the invention’ or is not recognized as solving the problem solved by the claimed invention, [are] not ‘germane’ to a rejection under section 102.’ Twin Disc, Inc. v. United States, 231 USPQ 417, 424 (Cl. Ct. 1986)… A reference is no less anticipatory if, after disclosing the invention, the reference then disparages it. The question whether a reference "teaches away" from the invention is inapplicable to an anticipation analysis. Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The prior art was held to anticipate the claims even though it taught away from the claimed invention”.
Thus, Applicant’s position that Carnicer provides guidance and “teaches away” from the claimed methods is not applicable for anticipation analysis under 35 U.S.C. 102(a)(1) standard. Ziberna teaches diabetes impairs myocardial glucose uptake and glycolysis and plays a key role in the development of a cardiomyopathy. Ziberna induces diabetes in mGCH1 transgenic mice and once cardiac dysfunction developed and myocardial glucose oxidation increased, GLUT1 inhibitor (STF-31) is administered to abolish all differences between mGCH and WT (wildtype) diabetic mice. See, e.g., pp. A135, 3rd paragraph. Therefore, Ziberna discloses every limitation and anticipates the instant claims 1 – 4 and 7 – 11. Applicant’s remarks are not persuasive and the rejections are maintained.
Claim Objections
Claims 13 – 17 are objected to because of the following informalities:
Claim 13, line 4 of the claim: The phrase “… glinides, sulfonylurea, thiazolidinedione, and combinations thereof” is grammatically incorrect because it does not recite proper language for the Markush groups of alternatives. The use of the conjunction “and” to claim the combinations of the second therapeutic agent is incorrect. In order to overcome the objection, Applicant may amend the phrase as follows: “… glinides, sulfonylurea, and thiazolidinedione, or combinations thereof”.
Claim 14, line 2 of the claim: The use of the comma (,) after the phrase “SGLT2 inhibitor” is redundant and grammatically incorrect. In order to overcome the objection, Applicant may amend to delete the comma (,).
Claim 15, line 2 of the claim: The use of the comma (,) after the phrase “GLP1 receptor agonist” is redundant and grammatically incorrect. In order to overcome the objection, Applicant may amend to delete the comma (,).
Claim 16, lines 1-2 of the claim: The phrase “an incretin mimetics” is grammatically incorrect because the article “an” refers to a singular form, while the term “incretin mimetics” is recited in plural form. In order to overcome the objection, Applicant may amend as follows: “an incretin mimetic
Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claims 1 – 4 and 7 – 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ziberna K. et al., 200, Heart 2017;103: pp. A135-A136, published online June 5, 2017.
Ziberna et al. teach that myocardial glucose uptake and glycolysis are impaired and the heart exclusively uses fatty acids (FA) for ATP generation in the presence of diabetes (DM). Said maladaptation plays a key role in the development of a cardiomyopathy. See, e.g., pp. A135, 1st paragraph. Ziberna induces diabetes mellitus (DM) (type 2 diabetes) via multiple low-dose streptozotocin injections in mGCH1 transgenic mice. Once cardiac dysfunction developed and myocardial glucose oxidation increased, GLUT1 inhibitor (STF-31) is administered to abolish all differences between mGCH and WT (wildtype) diabetic mice. See, e.g., pp. A135, 3rd paragraph. Ziberna concludes that “a myocardial increase in BH4 and NOS activity is sufficient to maintain a favourable substrate utilisation and preserve cardiac mitochondrial function in the presence of DM”. See, e.g., See, e.g., pp. A135, 4th paragraph. Ziberna teaches new metabolic triggers of diabetic cardiomyopathy and new targets for BH4-based therapeutics. See, e.g., the bridging paragraph between pp. A135-A136.
The prior art anticipates the instant claims as presented below:
Claims 1 – 3, directed to a method of treating diabetic cardiomyopathy in a patient in need thereof comprising administering a therapeutically effective amount of GLUT1 inhibitor STF-31.
Claim 4, wherein STF-31 is administered intraperitoneally (parenteral route).
Claim 7, wherein the patient is suffering from type 2 diabetes.
Claims 8 – 9, wherein STF-31 is administered after the patient is diagnosed with diabetes, and the patient experiences cardiac dysfunction.
Claims 10 – 11, wherein STF-31 is administered at least once (daily).
Claim Rejections - 35 USC § 103
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Ziberna K. et al., 200, Heart 2017;103: pp. A135-A136, published online June 5, 2017, as applied to claims 1 – 4 and 7 – 11 above, in view of Xintaropoulou et al., Oncotarget (2015), 6 (28), pp. 25677-25695.
Determining the scope and contents of the prior art
Ziberna et al. teach that myocardial glucose uptake and glycolysis are impaired and the heart exclusively uses fatty acids (FA) for ATP generation in the presence of diabetes (DM). Said maladaptation plays a key role in the development of a cardiomyopathy. See, e.g., pp. A135, 1st paragraph. Ziberna induces diabetes mellitus (DM) (type 2 diabetes) via multiple low-dose streptozotocin injections in mGCH1 transgenic mice. Once cardiac dysfunction developed and myocardial glucose oxidation increased, GLUT1 inhibitor (STF-31) is administered to abolish all differences between mGCH and WT (wildtype) diabetic mice. See, e.g., pp. A135, 3rd paragraph. Ziberna concludes that “a myocardial increase in BH4 and NOS activity is sufficient to maintain a favourable substrate utilisation and preserve cardiac mitochondrial function in the presence of DM”. See, e.g., See, e.g., pp. A135, 4th paragraph. Ziberna teaches new metabolic triggers of diabetic cardiomyopathy and new targets for BH4-based therapeutics. See, e.g., the bridging paragraph between pp. A135-A136.
Ziberna does not teach that STF-31 is administered as a plurality of doses.
Xintaropoulou et al. teach using GLUT1 inhibitors to inhibit the glycolysis pathway molecules and treat several breast and ovarian cancer cell lines. See, e.g., Abstract. Xintaropoulou teaches that GLUT1 inhibitors, including STF31 and WZB117, were administered in four breast and four ovarian cancer cell lines for a treatment period of 5 days. See, e.g., pp. 25679, 4th – 5th paragraphs, pp. 25680, 1st paragraph, and Table 1. The data (see, e.g., Table 1) is presented below:
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95
800
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95
794
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Ascertaining the differences between the prior art and the claims at issue
Compared to the instant claim 5, Ziberna et al. do not teach that STF-31 is administered as a plurality of doses.
Rationale for a prima face case of obviousness
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary
skill to modify the prior art reference or to combine prior art reference teachings to arrive at the
claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Xintaropoulou teaches administering GLUT1 inhibitor STF31 in breast and ovarian cancer cell lines for a treatment period of 5 days. See, e.g., pp. 25679, 4th – 5th paragraphs, pp. 25680, 1st paragraph, and Table 1. A person having ordinary skill in the art would have been motivated to perform routine experimentation to administer more than one dose of STF-31 to the patient because Xintaropoulou identifies STF31 as a lead compound and administering said compound for a treatment period of 5 days. The PHOSITA would have a reasonable expectation that administering plurality of doses of STF31 could also successfully treat diabetic cardiomyopathy in patients.
Claims 6, 12 – 13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Ziberna K. et al., 200, Heart 2017;103: pp. A135-A136, published online June 5, 2017, as applied to claims 1 – 5 and 7 – 11 above, in view of Liu et al., Endocrine Connection (2019), 8: pp. 277-288.
Determining the scope and contents of the prior art
Ziberna et al. teach that myocardial glucose uptake and glycolysis are impaired and the heart exclusively uses fatty acids (FA) for ATP generation in the presence of diabetes (DM). Said maladaptation plays a key role in the development of a cardiomyopathy. See, e.g., pp. A135, 1st paragraph. Ziberna induces diabetes mellitus (DM) (type 2 diabetes) via multiple low-dose streptozotocin injections in mGCH1 transgenic mice. Once cardiac dysfunction developed and myocardial glucose oxidation increased, GLUT1 inhibitor (STF-31) is administered to abolish all differences between mGCH and WT (wildtype) diabetic mice. See, e.g., pp. A135, 3rd paragraph. Ziberna concludes that “a myocardial increase in BH4 and NOS activity is sufficient to maintain a favourable substrate utilisation and preserve cardiac mitochondrial function in the presence of DM”. See, e.g., See, e.g., pp. A135, 4th paragraph. Ziberna teaches new metabolic triggers of diabetic cardiomyopathy and new targets for BH4-based therapeutics. See, e.g., the bridging paragraph between pp. A135-A136.
Ziberna does not teach co-administering STF-31 with one or more second therapeutic agents, specifically an incretin mimetic (e.g., glucagon-like peptide 1 receptor agonist (GLP-1 RA) or a dipeptidyl peptidase-4 (DPP-4) inhibitor).
Liu et al. teach “[i]ncretin-based drugs, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP-4) inhibitors, may offer an opportunity to avoid these side effects. Theoretically, GLP-1 RAs are structurally and functionally similar to GLP-1 and can mimic the effects of GLP-1, such as augmenting glucose-dependent insulin secretion, suppressing glucagon secretion, delaying gastric emptying and finally enhancing blood glucose management with weight loss”. See, e.g., pp. 278, 1st paragraph. Liu et al. evaluate the combination of insulin and incretin-based therapy in subjects with type 1 diabetes. See, e.g., pp. 278, 2nd paragraph.
Ascertaining the differences between the prior art and the claims at issue
Compared to the instant claims, Ziberna et al. do not teach the method further comprising co-administering one or more second therapeutic agents, specifically an incretin mimetic (e.g., glucagon-like peptide 1 receptor agonist (GLP-1 RA) or a dipeptidyl peptidase-4 (DPP-4) inhibitor).
Rationale for a prima face case of obviousness
According to MPEP §2141(III), two of the rationales in the KSR decision states “(A)
Combining Prior Art Elements According to Known Methods To Yield Predictable Results…
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary
skill to modify the prior art reference or to combine prior art reference teachings to arrive at the
claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Liu et al. teach administering insulin in combination with incretin-based therapy in subjects with type 1 diabetes. See, e.g., pp. 278, 2nd paragraph. Liu further teaches that the co-administration reduced the total daily insulin dose in patients with type-1 diabetes (T1DM). See, e.g., pp. 281, 3rd paragraph. MPEP §2144.06(I) further states:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”.
In view of In re Kerkhoven, a person having ordinary skill in the art would have been motivated to co-administer STF31 with incretin-based drugs because Liu teaches co-administering incretin-based drugs for the purpose of treating patients with type 1 diabetes (T1DM). Since these compounds have been generally known as antidiabetic drugs, the PHOSITA would find it advantageous to co-administer STF31 and incretin mimetic and treat diabetic cardiomyopathy in patients with type 1 diabetes.
Thus, the prior art renders the instant claims prima facie obvious.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Ziberna K. et al., 200, Heart 2017;103: pp. A135-A136, published online June 5, 2017 in view of Xintaropoulou et al., Oncotarget (2015), 6 (28), pp. 25677-25695, as applied to claims 1 – 5 and 7 – 11 above.
Determining the scope and contents of the prior art
Ziberna et al. teach that myocardial glucose uptake and glycolysis are impaired and the heart exclusively uses fatty acids (FA) for ATP generation in the presence of diabetes (DM). Said maladaptation plays a key role in the development of a cardiomyopathy. See, e.g., pp. A135, 1st paragraph. Ziberna induces diabetes mellitus (DM) (type 2 diabetes) via multiple low-dose streptozotocin injections in mGCH1 transgenic mice. Once cardiac dysfunction developed and myocardial glucose oxidation increased, GLUT1 inhibitor (STF-31) is administered to abolish all differences between mGCH and WT (wildtype) diabetic mice. See, e.g., pp. A135, 3rd paragraph. Ziberna concludes that “a myocardial increase in BH4 and NOS activity is sufficient to maintain a favourable substrate utilisation and preserve cardiac mitochondrial function in the presence of DM”. See, e.g., See, e.g., pp. A135, 4th paragraph. Ziberna teaches new metabolic triggers of diabetic cardiomyopathy and new targets for BH4-based therapeutics. See, e.g., the bridging paragraph between pp. A135-A136.
Ziberna does not teach co-administering STF-31 with one or more second therapeutic agents, specifically a biguanide (e.g., metformin).
Xintaropoulou et al. teach using GLUT1 inhibitors to inhibit the glycolysis pathway molecules and treat several breast and ovarian cancer cell lines. See, e.g., Abstract. Xintaropoulou also teaches “[a] second objective was to examine the effect of selected
glycolytic inhibitors in combination with the antidiabetic drug metformin”. See, e.g., pp. 25688, 2nd paragraph. Xintaropoulou specifically teaches testing a range of different concentrations of STF31 in combination with a constant fixed concentration of metformin. See, e.g., pp. 25685, 2nd paragraph.
Ascertaining the differences between the prior art and the claims at issue
Compared to the instant claims, Ziberna et al. do not teach the method further comprising co-administering one or more second therapeutic agents, specifically a biguanide (e.g., metformin).
Rationale for a prima face case of obviousness
According to MPEP §2141(III), two of the rationales in the KSR decision states “(A)
Combining Prior Art Elements According to Known Methods To Yield Predictable Results…
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary
skill to modify the prior art reference or to combine prior art reference teachings to arrive at the
claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Xintaropoulou teaches administering STF31 in combination with the antidiabetic drug metformin. See, e.g., pp. 25688, 2nd paragraph. Xintaropoulou further teaches “[m]etformin enhanced the potency of… STF31… to inhibit cancer cell proliferation compared to the effect of these drugs individually”. See, e.g., pp. 25685, 2nd paragraph, and Figures 7A and 7B. MPEP §2144.06(I) further states:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”.
In view of In re Kerkhoven, a person having ordinary skill in the art would have been motivated to co-administer STF-31 with metformin (biguanide) because these compounds have been generally known as antidiabetic drugs. Xintaropoulou teaches co-administering STF-31 and metformin for the purpose of treating breast and ovarian cancer cell lines and the PHOSITA would have expected that their co-administration could also successfully treat diabetic cardiomyopathy in patients.
Thus, the prior art renders the instant claims prima facie obvious.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sagar Patel whose telephone number is (571)272-1317. The examiner can normally be reached Monday - Friday: 9am to 5pm EST.
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/Sagar Patel/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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