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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
This application is a 371 of PCT/EP2021/084070 filed 12/02/2021.
This application also claim foreign benefit of EPO EP20306504.0 filed 12/04/2020.
Accordingly, claims 1-11 and 13-21 of the instant application are afforded the effective filing date of 12/04/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted 06/02/2023 has been considered by the examiner and initialed copies of the IDS are included with the mailing of this office action.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6 and 14-16, in the reply filed on 03/16/2026 is acknowledged.
The traversal is on the ground(s) that the claims have been amended to “require ranitidine compositions that contain "less than 320 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C during 5 days," and such technical feature is not disclosed or suggested in the cited prior art of Sokol. Thus, Applicant alleged that the claims have unity of invention for the additional reason that the Written Opinion from the International Search Authority have found that the claims had unity of invention due the claims are novel, have inventive step and industrial applicability. (Remarks filed 03/16/2026, page 7-8).
This is not found persuasive because the amount of “less than 320 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days” has been taught and render obvious by the teachings from Parr et al (Journal of Pharmaceutical and Biomedical Analysis, 2019, 164: 536-549), and Winston and Strawn (“FDA Provides Guidance to Manufacturers for Controlling Nitrosamine Impurities in Human Drugs.” Published date: 18 September 2020, pages 1-4), in which Parr established that nitrosodimethylamine (NDMA) is a known impurity in ranitidine products (Parr: Abstract; pages 538-544), and per Winston and Strawn, the acceptable intake limit according to the FDA for NDMA in drug products such as ranitidine products is less than 96 ng/day (below 320 ppb) (Winston and Strawn: pages 1-3), which reads on the claimed amount of “less than 320 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts.” Thus, ordinary artisan knowing the drawbacks of NDMA impurities in ranitidine products would have looked to providing a ranitidine composition of Sokol which meets the FDA’s guideline for drug products by providing a ranitidine composition of Sokol that contains less than 320 ppb of NDMA. Accordingly, lack of unity invention remains between Groups I-III of the Restriction Requirement dated 01/16/2026 because the combined teachings of Sokol, Parr, and Winston and Strawn have taught and rendered obvious the common technical feature as recited in claim 1 and thus, said common technical feature remains not a special technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-11, 13, and 17-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected groups/inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/16/2026.
Status of the Claims
Claims 1-11 and 13-21 are pending in this instant application, of which claims 7-11, 13, and 17-21 are withdrawn at this time being drawn to a nonelected groups/inventions.
Claims 1-6 and 14-16 are examined herein on the merits for patentability.
Claim Objections
Claim 2 is objected to because of the following informalities: it is suggested that all the dashes (-) be removed from claim 2. It is noted that [w]here a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m). Appropriate correction is required.
Claim 5 is objected to because of the following informalities: claim 5 recites multiple improper Markush groups languages. When materials recited in a claim are so related as to constitute a proper Markush groups, they may be recited in the conventional manner, or alternatively. For example, if “wherein R is a material selected from the group consisting of A, B, C and D” is a proper limitation, then “wherein R is A, B, C or D” shall also be considered proper. Appropriate correction is required.
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 1-6 and 14-16 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.
Regarding claim 1, the recitation of “comprising” following “pharmaceutical acceptable salts” renders claim 1 indefinite because it is unclear if the claimed features of “less than 1 ppm, less than 900 ppb, less than 600 ppb, or less than 300 ppb of iron species by weight with respect to the total dry weight of the composition, wherein said composition comprises less than 320 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days” that follows “comprising” are features that are part of the “one of its pharmaceutical acceptable salts” or the composition. To obviate this indefinite rejection, it is suggested that claim 1 is amended as follows: “A composition comprising ranitidine or one of its pharmaceutically acceptable salts, wherein said composition comprises less than 1 ppm, less than 900 ppb, less than 600 ppb, or less than 300 ppb of iron species by weight with respect to the total dry weight of the composition, and wherein said composition comprises less than 320 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days.” Clarification by amendment in claim 1 is required.
Regarding claim 2, the recitation of “comprising” in the fourth (4th) line of the claim renders claim 2 indefinite because it is unclear if the claimed features following “comprising” are features that are part of the composition, the “one of its pharmaceutical acceptable salts” or the N-nitrosodimethylamine (NDMA). To obviate this indefinite rejection, it is suggested that the term “containing” (in line 1 of claim 2) be amended to “comprising” and the term “comprising” (in line 4 of claim 2) be amended to “, wherein said composition comprises: …” Clarification by amendment in claim 1 is required.
Claims 3-6 and 14-16 are also rejected as they depend from indefinite claims 1 and 2, respectively.
As a result, claims 1-6 and 14-16 do not clearly set forth the metes and bounds of patent protection desired.
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(s) 1 and 3-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over of Sokol et al (Acta Poloniae Pharmaceutica—Drug Research, 2011, 68(2): 169-177; previously cited) in view of Parr et al (Journal of Pharmaceutical and Biomedical Analysis, 2019, 164: 536-549) and Winston and Strawn (“FDA Provides Guidance to Manufacturers for Controlling Nitrosamine Impurities in Human Drugs.” Published date: 18 September 2020, pages 1-4).
Regarding claims 1 and 3-6, Sokol teaches a pharmaceutical composition containing ranitidine HCl and trace amount of iron (Fe(II)) (Abstract; pages 169, right column to page 176, right column), thereby “trace amount” meets the claimed less 1 ppm of iron species.
While Sokol does not expressly teach the composition comprises less than 320 ppb or less than 160 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days,” as recited in claims 1 and 3, respectively, it would have been obvious to provide the composition of Sokol such that the amount of NDMA is less than 320 ppb or less than 160 ppb by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days per guidance from Parr, and Winston and Strawn.
Parr teaches that nitrosodimethylamine (NDMA) is a known impurity in ranitidine products, especially ranitidine has been reported to show very high molar conversion to NDMA in oxidizing conditions and thus, exposure to air and light may also lead to the formation of NDMA during API storage (Abstract; pages 538-544).
Winston and Strawn teaches that nitrosodimethylamine (NDMA) is a known impurity in ranitidine products, and the acceptable intake limit according to the FDA for NDMA in drug products such as ranitidine products is less than 96 ng/day (less 320 ppb) (pages 1-3).
It would have been obvious to one of ordinary skill in art to provide the composition of Sokol such that the amount of NDMA in the composition is less than 320 ppb or less than 160 ppb by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because ordinary artisan knowing the drawbacks of NDMA impurities in ranitidine products during storage per Parr would have looked to providing a ranitidine composition Sokol which meets the FDA’s guideline for drug products per Winston and Strawn, by providing a ranitidine composition of Sokol that contains less than 320 ppb of NDMA after an exposure to 70°C for 5 days by optimizing the manufacturing conditions to prevent unacceptable levels of NDMA in ranitidine products, achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 2 and 14-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over of Sokol et al (Acta Poloniae Pharmaceutica—Drug Research, 2011, 68(2): 169-177; previously cited) in view of Parr et al (Journal of Pharmaceutical and Biomedical Analysis, 2019, 164: 536-549), Winston and Strawn (“FDA Provides Guidance to Manufacturers for Controlling Nitrosamine Impurities in Human Drugs.” Published date: 18 September 2020, pages 1-4), and Pilgaonkar et al (US 2017/0128379 A1).
Regarding claims 2 and 14-16, Sokol teaches a pharmaceutical composition containing ranitidine HCl and trace amount of iron (Fe(II)) (Abstract; pages 169, right column to page 176, right column), thereby “trace amount” meets the claimed less 1 ppm of iron species.
While Sokol does not expressly teach the composition comprises less than 320 ppb or less than 160 ppb of N-nitrosodimethylamine (NDMA) by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days,” as recited in claims 2 and 14, respectively, it would have been obvious to provide the composition of Sokol such that the amount of NDMA is less than 320 ppb or less than 160 ppb by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days per guidance from Parr, and Winston and Strawn.
Parr teaches that nitrosodimethylamine (NDMA) is a known impurity in ranitidine products, especially ranitidine has been reported to show very high molar conversion to NDMA in oxidizing conditions and thus, exposure to air and light may also lead to the formation of NDMA during API storage (Abstract; pages 538-544).
Winston and Strawn teaches that nitrosodimethylamine (NDMA) is a known impurity in ranitidine products, and the acceptable intake limit according to the FDA for NDMA in drug products such as ranitidine products is less than 96 ng/day (less 320 ppb) (pages 1-3).
It would have been obvious to one of ordinary skill in art to provide the composition of Sokol such that the amount of NDMA in the composition is less than 320 ppb or less than 160 ppb by weight with respect to the total dry weight of ranitidine or its pharmaceutically acceptable salts after an exposure to 70°C for 5 days, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because ordinary artisan knowing the drawbacks of NDMA impurities in ranitidine products during storage per Parr would have looked to providing a ranitidine composition Sokol which meets the FDA’s guideline for drug products per Winston and Strawn, by providing a ranitidine composition of Sokol that contains less than 320 ppb of NDMA after an exposure to 70°C for 5 days by optimizing the manufacturing conditions to prevent unacceptable levels of NDMA in ranitidine products, achieve Applicant’s claimed invention with reasonable expectation of success.
With respect to the chelating agent of claim 2, Pilgaonkar teaches a pharmaceutical composition comprising an active ingredient such as ranitidine, and at least one pharmaceutically acceptable excipient including stabilizers such as chelating agents ([0014]-[0032]; claim 4). It would have been obvious to one of ordinary skill in the art to include a chelating agent in the pharmaceutical composition containing ranitidine of Sokol, and produce the claimed invention. One of ordinary skill in the art would have been motivated do so because Pilgaonkar provided the guidance for including a chelating agent in a pharmaceutical composition containing an active ingredient such as ranitidine, as chelating agents are known pharmaceutically acceptable excipient conventionally added to pharmaceutical preparation to inhibit or prevent degradation of the drug during manufacturing process and over shelf life of the composition per Pilgaonkar ([0016]). Thus, an ordinary artisan seeking to inhibit or prevent degradation of the ranitidine during manufacturing process and over shelf life of the composition, would have looked to including conventionally known pharmaceutically acceptable excipients including chelating agent in the pharmaceutical composition containing ranitidine of Sokol, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the in art the before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613
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