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 .
DETAILED ACTION
2. Claims 13 – 28 are pending in this application. Applicant’s preliminary amendment, submitted May 8, 2024, is entered, wherein claims 13 – 28 are new and claims 1 – 12 are canceled.
Priority
3. This application is a national stage application of PCT/EP2021/078691, filed October 15, 2021, which claims benefit of foreign priority document GB2016450.5, filed October 16, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/12/2023 and 08/12/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 21 – 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
a. Claims 21 – 22 recite the term “preferably”. These claims are indefinite because the inclusion of the term “preferably” renders the scope of the claim ambiguous. The use of “preferably” introduces uncertainty as to whether the narrower option of species is intended to be a required limitation or merely a suggested, non-limiting embodiment of the broader range. The use of the term prevents one of ordinary skill in the art from determining the precise boundaries of the claims.
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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 13 – 18, and 24 – 27 are rejected under 35 U.S.C. 103 as being unpatentable over Rebel Distributor Corp (Metformin Hydrochloride, 2011, Reference included with PTO-892) in view of Niazi (Crc Press, 2004, Reference included with PTO-892) and Wasylaschuk et al. (Journal of Pharmaceutical Sciences, 2007, Vol. 96, Issue 1, page 106 – 116, Reference included with PTO-892).
a. Regarding claims 13 – 18, and 24 – 27, Rebel Distributor Corp teaches information about metformin hydrochloride extended-release tablets. Metformin hydrochloride extended-release tablets contain the inactive ingredients, which are xanthan gum, Hypromellose, sodium carbonate, povidone, talc, colloidal silicon dioxide, and magnesium stearate ( page 1, para. 4). Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose (page 1, para. 7).
However, Rebel Distributor Corp does not disclose the composition comprising more than 50 ppm of peroxide impurities and less than 50 ppm of an amine impurity.
Niazi teaches the amount of sodium carbonate used in one formulation is 5 mg in a total of 208 mg composition (page 141). Niazi explicitly teaches the amount of povidone used in a metformin hydrochloride extended-release tablet is 51.50 mg in a total of 1030 mg composition (page 204).
Wasylaschuk et al. teach the hydroperoxide (HPO) impurity levels of common pharmaceutical excipients. Of the four excipients with substantial HPO levels, povidone, PEG 400, and HPC contain a mixture of hydrogen peroxide and organic HPOs while PS80 contains predominantly organic HPOs (Abstract). HPOs can be an “organic” hydroperoxide (ROOH), wherein R is a carbon atom, or hydrogen peroxide (H2O2) (page 107, Left Col., para. 1). Wasylaschuk et al. monitor the “total” HPO content (ROOH + H2O2) (page 107, Left Col., para. 2). The average level of HPOs found in povidone is 7300 nmole/g (page 109, Table 1). The distribution of H2O2 in HPOs is between 20 – 60% (page 112, Table 7).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the metformin hydrochloride extended-release tablets comprising metformin hydrochloride, sodium carbonate, and povidone as taught by Rebel Distributor Corp with the amount of sodium carbonate and povidone used in the formulation in view of Niazi because Niazi teaches the amount of sodium carbonate and povidone used in different formulations. One would have been motivated to use the amount of sodium carbonate disclosed by Niazi, which is 2.4 wt%, as a general guidance to indicate the safe amount of sodium carbonate used in subject even the formulation is not for metformin hydrochloride. One would also have been motivated to use the amount of povidone disclosed by Niazi because Niazi teaches the amount of povidone used in a metformin hydrochloride extended-release tablet, thereby, yielding a predictable result. For the amount of sodium carbonate and povidone, one would have performed routine experimentation to discover the best quantities for optimal treatment characteristics. For the composition comprising more than 50 ppm of peroxide impurities, the average HPO content of povidone and the lowest distribution of H2O2 in the HPOs disclosed by Wasylaschuk et al. are used for the calculation. Based on the calculation, there are 1460 nmole H2O2 in 1 g of povidone. When 51.5 mg povidone is used, the amount of H2O2 is 75.19 nmole. Therefore, the lowest amount of H2O2 presented in the formulation with 51.5 mg povidone is 49.7 ppm. The HPO content will be expected to be greater than 50 ppm when ROOH is also taken into consideration. Moreover, it is known in the art that a pharmaceutical composition is manufactured by mixing and formulating. As Rebel Distributor Corp teaches the same components, the formulation will inherently achieve the reduction of an amine impurity. Therefore, the amine impurity is expected to be less than 50 ppm as claimed. One of the ordinary skill in the art would have had a reasonable expectation of success to combine the metformin hydrochloride extended-release tablets comprising metformin hydrochloride, sodium carbonate, and povidone as taught by Rebel Distributor Corp with the amount of sodium carbonate and povidone used in the formulation in view of Niazi because Rebel Distributor Corp teaches the exact composition and Niazi provides the amount of sodium carbonate and povidone commonly used. Finally, Wasylaschuk et al. teach information to determine the amount of peroxide impurities.
Claims 19 – 23 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Rebel Distributor Corp (Metformin Hydrochloride, 2011, Reference included with PTO-892) in view of Niazi (Crc Press, 2004, Reference included with PTO-892) and Wasylaschuk et al. (Journal of Pharmaceutical Sciences, 2007, Vol. 96, Issue 1, page 106 – 116, Reference included with PTO-892) as applied to claims 13 – 18 and 24 – 27 above, and further in view of Qternmet (Highlights of Prescribing Information, 2019, Reference included with PTO-892).
b. Regarding claims 19 – 23 and 28, the references teach the limitations discussed above.
However, these references do not teach the composition further comprising an anti-diabetic compound, wherein the anti-diabetic compound is SGLT2 inhibitor and/or DPP-4 inhibitor, wherein the SGLT2 inhibitor is dapagliflozin and the DPP-4 inhibitor is saxagliptin.
Oternmet teaches a composition comprising a SGLT2 inhibitor, a DPP-4 inhibitor, and a biguanide as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (page 1, Left Col., Indications and Usage), wherein the SGLT2 inhibitor is dapagliflozin, the DPP-4 inhibitor is saxagliptin, and the biguanide is metformin HCl (page 1, Left Col., Dosage and Strengths).
It would have been prima facie obvious to combine the metformin hydrochloride extended-release tablets comprising metformin hydrochloride, sodium carbonate, and povidone as taught by Rebel Distributor Corp with dapagliflozin and saxagliptin in view of Oternmet because such combination is already known in the art. It would have been obvious to combine because these references teach that the combination or the drugs alone are used for treating type 2 diabetes. It would have been obvious to combine them to treat the same disease. One of the ordinary skill in the art would have had a reasonable expectation of success to combine the metformin hydrochloride extended-release tablets comprising metformin hydrochloride, sodium carbonate, and povidone as taught by Rebel Distributor Corp with dapagliflozin and saxagliptin in view of Oternmet because it is well known to combine drugs to treat the same disease and Qternmet’s disclosure indicates that such combination is already known in the art.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693