DETAILED ACTION
Claims 9-21, submitted 09 March 2026, are pending in the application. Claims 9-12 are withdrawn. Claim 21 is new. Claims 13-21 are under examination in the instant Office 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 .
Election/Restrictions
Applicant’s election without traverse of Group III, claims 13-21, the elected species of pharmaceutical ingredient, metformin, and the elected species of NDMA inhibitor, sodium metabisulfite, in the reply filed on 09 March 2026 is acknowledged.
Claims 9-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09 March 2026.
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.
Claims 13-16 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Narang et al. (US PG-PUB 2013/0224296 A1) in view of Kumar et al. ("Metformin and nitrosamine impurities." International Journal of Research in Medical Sciences 8.10 (2020): 3778.) and Tian et al. ("Nitrite scavenging and inhibition of N-nitrosamines formation by phenolic extracts from Diospyros lotus L. leaves and active ingredients." Natural Product Communications 15.9 (2020): 1934578X20961186.).
Narang teaches a pharmaceutical composition comprising a tablet core that comprises a binder, wetting agent, a lubricant, and at least one antidiabetic or pharmaceutically acceptable salt thereof, wherein the antidiabetic is metformin (paragraph 0052). In that same paragraph, Narang teaches wherein a first layer coats the tablet core and comprises at least one water soluble antioxidant. This reference additionally teaches wherein a variety of water-soluble antioxidants can be used including ascorbic acid, propyl gallate, sodium sulfite, sodium metabisulfite, and sodium bisulfite (paragraph 0030). Narang does not teach wherein the antioxidants used are an inhibitor of N-nitrosodimethylamine, however, the specification teaches wherein sodium metabisulfite and sodium dithionite are antioxidants on page 5 in Example 2. Thus, the pharmaceutical composition taught by Narang reads, in part, on the limitations of the instant claims.
Narang does not teach a similar method of use to that of instant claim 13, as the pharmaceutical composition of the reference is used in a method to prevent or reduce N-formylation (paragraph 0033). However, Kumar teaches that, “Dimethyl amine (DMA), which is a precursor of NDMA, is used in the synthesis of Metformin. Thus, there is always a possibility of NDMA showing up in lots of Metformin.”(pg. 3780, Section “Source of NDMA in Metformin”, Right Col., 1st paragraph) and that “NDMA may be formed due to contact with oxidants in the process of synthesis of metformin like valsartan.”(pg. 3781, Section “Source of NDMA in Metformin”, Left Col., 1st paragraph). Additionally, Tian states that, “nitrite scavenging is an effective way to inhibit NAs (N-nitrosamines) formation”, and also teaches that the materials that could scavenge nitrite or inhibit NA formation have been reported in natural ingredients such as plant phenolics and α-tocopherol. Tian recites that “These findings suggested that plant phenolics possess strong antioxidant, nitrite scavenging, and inhibition of NAs formation activities, and the nitrite-scavenging activity was more closely related to their antioxidant activity. (pg. 1-2, Section, “Introduction”, Right Col. to Left Col. of pg. 1, 1st paragraph and Left Col. of pg. 2, 1st paragraph).
Therefore, it would have been prima facie obvious for a person having ordinary skill in the art to combine the teachings of Narang with the teachings of Kumar and Tian to inhibit the formation of N-nitrosodimethylamine (NDMA) in a pharmaceutical composition by combining an active pharmaceutical ingredient (API), wherein the API is metformin, with an inhibitor of NDMA to form a pharmaceutical composition because Kumar teaches that NDMA may increase the risk of cancer if people are exposed to it above the acceptable level and over a long period of time (pg. 3779, Section, “Metformin, NDMA and FDA recall”, Right Col., 1st paragraph). An ordinarily skilled artisan would have had a reasonable expectation of success because Tian teaches that NAs can be formed by the reaction of nitrite reagents and secondary amines in vitro and in vivo (pg. 1, Section, “Introduction”, Left Col. 1st paragraph) and also that the nitrite-scavenging activities of the phenolics were more closely related to their antioxidant activities. Additionally, Narang teaches an API tablet core with a layer of a water-soluble antioxidant. Thus, it would have been prima facie for one of ordinary skill in the art to combine the teachings of Narang, Kumar and Tien, to arrive at the instantly claimed invention.
With respect to claim 14, Narang teaches wherein a variety of water-soluble antioxidants can be used to include ascorbic acid, propyl gallate, sodium sulfite, sodium metabisulfite, and sodium bisulfite (paragraph 0030).
With respect to claim 15, Narang teaches wherein the composition comprises excipients where the excipients comprise a binder, a filler, a lubricant, or a release modifier shown in Table 14 below.
Table 14 (pg. 18-19)
PNG
media_image1.png
290
508
media_image1.png
Greyscale
Regarding claim 21, Narang teaches wherein the API comprises metformin hydrochloride (paragraph 0077).
Allowable Subject Matter
Claims 17-20 are 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.
The closest prior art is Narang, which teaches a pharmaceutical composition comprising a tablet core that comprises a binder, wetting agent, a lubricant, and at least one antidiabetic or pharmaceutically acceptable salt thereof, wherein the antidiabetic is metformin and wherein a layer coats the tablet core and comprises at least one water soluble antioxidant (paragraph 0052). However, Narang does not teach a similar use of said pharmaceutical composition and further does not teach wherein the pharmaceutical composition comprises less than 40 ng NMDA when administered at the maximum daily dose per the respective drug label, which would lead to an invention similar to that of the Applicants.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./ Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/ Supervisory Patent Examiner, Art Unit 1622