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 Claims
The amendments to the claims filed February 18, 2026 are acknowledged and entered. Claims 1-15 are pending.
Priority
This application is a 371 of PCT/CN2021/138255, filed December 15, 2021, which claims priority of CN 202011573509.7, filed December 28, 2020.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statements filed on February 5 and February 9, 2026. All references have been considered except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which applicant may become aware of in the specification.
Election/Restriction
Applicant’s election without traverse of Group I (claims 1-7 drawn to a pharmaceutical composition comprising a pyrroloquinoline quinone trilithium salt nonahydrate compound, wherein the pyrroloquinoline quinone trilithium salt nonahydrate compound is in a crystalline form, and the pyrroloquinoline quinone trilithium salt nonahydrate compound has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 2ɵ diffraction angles of 6.2 ±0.2, 7.4 ±0.2, 7.9 ±0.2 and 23.6 ±0.2) in the reply filed on February 18, 2026 is acknowledged. Claims 8-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 18, 2026.
Claim Objections
The claims are objected to because the lines are crowded too closely together, making reading difficult. Substitute claims with lines one and one-half or double spaced on good quality paper are required. See 37 CFR 1.52(b).
Claim 1 objected to because of the following informalities:
Line 4 of the claim recites “1.0 part by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound” and should instead recite “1.0 part by weight of the pyrroloquinoline quinone trilithium salt nonahydrate compound”
Appropriate correction is required.
Claim Rejections - 35 USC § 112b
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.
Claim 4 is 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. The claims are indefinite for the reasons that follow:
Claim 4 recites the limitations “0.6 part by weight … of pregelatinized starch; 0.36 part by weight to 0.96 part by weight of microcrystalline cellulose; and 0 part by weight to 0.06 part by weight of magnesium stearate" in lines 3-6. There is insufficient antecedent basis for these limitations in the claim because claim 4 depends from claim 3 which recites the additional pharmaceutically acceptable excipient is of 2.0 parts by weight to 4.0 parts by weight. The excipient ranges set forth in claim 4 are less than 2.0 parts by weight set forth in claim 3, are outside of the scope of claim 3, and therefore lack antecedent basis.
Claim Rejections - 35 USC § 112d
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 depends from claim 2 and recites characterized in that the colloidal silica can be added through an internal addition method or an internal-external addition method; and the additional pharmaceutically acceptable excipient can be added through an internal addition method or an internal-external addition method.
Claim 6 depends from claim 5 and recites characterized in that when the colloidal silica is added through the internal-external addition method, the weight ratio of the internally added colloidal silica to the externally added colloidal silica is greater than 3:1; and when the additional pharmaceutically acceptable excipient is added through the internal-external addition method, the weight ratio of the internally added additional pharmaceutically acceptable excipient to the externally added additional pharmaceutically acceptable excipient is greater than 3:1.
Claims 7 depends from claim 5 and recites characterized in that the additional pharmaceutically acceptable excipient which can be added through the internal addition method is selected from one or more of starch, lactose, microcrystalline cellulose, mannitol, croscarmellose sodium, copovidone, and magnesium stearate; and the additional pharmaceutically acceptable excipient which can be added through the external addition method is selected from one or more of microcrystalline cellulose, croscarmellose sodium, and magnesium stearate.
Claims 5-7 recite characteristics of how the composition of claim 2 is made. How the composition is made (e.g. characterized in that the colloidal silica can be added through an internal addition method…) does not change the chemical composition (structure) of the claimed invention. How the composition is made is thus not regarded as a further limitation to the composition of claim 2 because it does not provide any additional structural limitation. Claims 5-7 are therefore rejected for failing to further limit the subject matter of the claim upon which they depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (US9,738,639 B2; published 2017) (hereinafter “Zhong”) in view of Tran et al. (International J of Pharmaceutics 556 (2019) 383-394)(hereinafter “Tran”).
Instant claim 1 is drawn to a composition comprising a pyrroloquinoline quinone trilithium salt nonahydrate compound, characterized in that the pharmaceutical composition comprises: 1.0 part by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound; and a pharmaceutically acceptable excipient; the pharmaceutically acceptable excipient comprises: 0.16 part by weight to 0.48 part by weight of colloidal silica; wherein the pyrroloquinoline quinone trilithium salt compound has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 2ɵ diffraction angles of 6.2 ±0.2, 7.4 ±0.2, 7.9 ±0.2 and 23.6 ±0.2.
Instant claims 2-4 depend from claim 1 and recite additional excipients and parts by weights.
Instant claims 5-7 depend indirectly from claim 1 and recite characteristics of how the composition is made. How the composition is made (e.g. characterized in that the colloidal silica can be added through an internal addition method…) does not change the chemical composition (structure) of the claimed invention and is therefore not regarded as an additional limitation which can distinguish the invention from the prior art
Regarding claims 1-7, Zhong teaches a pharmaceutical composition comprising a pyrroloquinoline quinone trilithium salt nonahydrate compound and at least one pharmaceutically acceptable excipient, wherein the pyrroloquinoline quinone trilithium salt nonahydrate compound is in a crystalline form, and the pyrroloquinoline quinone trilithium salt nonahydrate compound has an X-ray powder diffraction pattern comprising characteristic diffraction peaks at 2ɵ diffraction angles of 6.2 ±0.2, 7.4 ±0.2, 7.9 ±0.2 and 23.6 ±0.2 (see claims 1 and 6; see col 1, lines 25-45: Formula (I), the full name of pyrroloquinoline quinine lithium salt is the trilithium derivative of pyrroloquinoline quinine; see Table 1 at col 5: Form B of pyrroloquinoline quinine lithium salt, XRPD at 6.222, 7.379, 7.941 and 23.631; see also pages 1-2 of the instant specification: Chinese invention patent applications 200910048873.9 and 201310270885.2 respectively disclose a lithium salt form and a nonahydrate crystalline form of the
pyrroloquinoline quinone compound. As described in Chinese invention patent application 201310270885.2, the crystalline form represented by Formula (I); the structure of Formula (I) is the trilithium salt nonahydrate compound; CN application no. 201310270885.2 corresponds to US9,738,639 B2). Zhong teaches wherein the excipients are selected from fillers, disintegrants, lubricants, binders and a combination of two or more thereof (claim 7). Zhong teaches wherein the excipients are starch, which includes pregelatinized forms, microcrystalline cellulose and magnesium stearate (claims 8 and 11).
Zhong is silent regarding colloidal silica and the parts by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound and parts by weight of both colloidal silica and other excipients of the claims (e.g. microcrystalline cellulose). However, Tran teaches pharmaceutical mixtures typically comprise a plurality of components and some of those are used specifically to modify the flow behavior of the blend. The flow properties of the mixture are a complex function of not only the mixture composition, but also the specific arrangement of the different component particles. The use of glidants to enhance the flow properties of pharmaceutical particulate blends for direct tablet compression is the typical application utilizing specific particle arrangement to improve flow. The small quantities of glidant substances (e.g. colloidal silica or talc) added to the formulation and blended together can improve the flow of the powder substantially and facilitate the capsule or tablet die filling (page 384, col 1, paragraph 3). Tran further teaches colloidal silica is one of the most efficient glidants and is commonly used to improve pharmaceutical blend flowability and that the optimal concentration of colloidal silica is 0.125-0.5% by weight (page 384, col 2, paragraph 2).
The difference between the prior art and the instant claims is that the instant claims require colloidal silica and specific parts by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound and parts by weight of both colloidal silica and other excipients (e.g. microcrystalline cellulose). However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the composition of Zhong into the claimed invention because colloidal silica, as disclosed by Tran, was commonly used to improve pharmaceutical blend flowability. Moreover, it would have been routine to modify the amount of each component in pharmaceutical composition of Zhong, which would include the claimed parts by weight, in order to achieve optimal blend flowability. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.) (see MPEP 2144.05). In the instant case, Tran disclosed that pharmaceutical mixtures typically comprise a plurality of components and some of those are used specifically to modify the flow behavior. Thus, a person of ordinary skill in the art would have been aware that a pharmaceutical composition was comprised of multiple components, that these components could be used to modify the flow behavior of the composition, and would have recognized that the flow behavior could be optimized through routine experimentation of varying the amount of each component in the mixture in order to achieve the optimal result.
One would have been motivated to modify Zhong with colloidal silica as a matter of enhancing flow properties of the composition in order to facilitate capsule or tablet die filling (see Tran). One would have been motivated to perform the routine optimization of varying the amount of each component in the composition as a matter of achieving the optimal flow behavior.
One would have had a reasonable expectation of success because at the time it was known that colloidal silica could be added to the formulation and blended together to improve the flow of the powder substantially and facilitate the capsule or tablet die filling.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,738,639 in view of in view of Tran et al. (International J of Pharmaceutics 556 (2019) 383-394)(hereinafter “Tran”).
Patent claim 1 is drawn to a pyrroloquinoline quinine lithium salt crystalline form B, characterized by an X-ray powder diffraction pattern with significant peaks at diffraction angles (2θ values) of about 6.222±0.2°, 7.379±0.2°, 7.941±0.2°, 23.631±0.2°.
Patent claim 6 depends from claim 1 and recites a pharmaceutical composition comprising the pyrroloquinoline quinine lithium salt crystalline form B according to claim 1 and at least one pharmaceutically acceptable excipients.
Patent claim 7 depends from claim 1 and recites the pharmaceutical composition of claim 6, wherein the excipients are selected from fillers, disintegrants, binders, lubricants and a combination of two or more thereof.
Patent claim 8 depends from claim 7 and recites wherein the fillers are selected from starch, lactose, crystalline cellulose, dextrin, mannitol, oxidase, calcium sulfate and a combination of two or more thereof.
Patent claim 11 depends from claim 7 and recites wherein the lubricants are selected from magnesium stearate, calcium stearate and a combination of two thereof.
The patent claims are silent regarding colloidal silica and the parts by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound and parts by weight of both colloidal silica and other excipients of the claims (e.g. microcrystalline cellulose). However, Tran teaches pharmaceutical mixtures typically comprise a plurality of components and some of those are used specifically to modify the flow behavior of the blend. The flow properties of the mixture are a complex function of not only the mixture composition, but also the specific arrangement of the different component particles. The use of glidants to enhance the flow properties of pharmaceutical particulate blends for direct tablet compression is the typical application utilizing specific particle arrangement to improve flow. The small quantities of glidant substances (e.g. colloidal silica or talc) added to the formulation and blended together can improve the flow of the powder substantially and facilitate the capsule or tablet die filling (page 384, col 1, paragraph 3). Tran further teaches colloidal silica is one of the most efficient glidants and is commonly used to improve pharmaceutical blend flowability and that the optimal concentration of colloidal silica is 0.125-0.5% by weight (page 384, col 2, paragraph 2).
The difference between the patent claims and the instant claims is that the instant claims require colloidal silica and specific parts by weight of pyrroloquinoline quinone trilithium salt nonahydrate compound and parts by weight colloidal silica and other excipients (e.g. microcrystalline cellulose). However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the patent claims into the claimed invention because colloidal silica, as disclosed by Tran, was commonly used to improve pharmaceutical blend flowability. Moreover, it would have been routine to modify the amount of each component in pharmaceutical composition of Zhong, which would include the claimed parts by weight, in order to achieve optimal blend flowability. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.) (see MPEP 2144.05). In the instant case, Tran disclosed that pharmaceutical mixtures typically comprise a plurality of components and some of those are used specifically to modify the flow behavior. Thus, a person of ordinary skill in the art would have been aware that a pharmaceutical composition was comprised of multiple components, that these components could be used to modify the flow behavior of the composition, and would have recognized that the flow behavior could be optimized through routine experimentation of varying the amount of each component in the mixture in order to achieve the optimal result.
One would have been motivated to modify the patent claims with colloidal silica as a matter of enhancing flow properties of the composition in order to facilitate capsule or tablet die filling. One would have been motivated to perform the routine optimization of varying the amount of each component in the composition as a matter of achieving the optimal flow behavior.
One would have had a reasonable expectation of success it was known that colloidal silica could be added to the formulation and blended together to improve the flow of the powder substantially and facilitate the capsule or tablet die filling.
Conclusion
No claim is allowed.
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March 19, 2026
/KEVIN S MARTIN/Examiner, Art Unit 1624