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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-5 and 9, drawn to a co-crystal of hydroxytyrosol and nicotinamide, wherein the co-crystal of hydroxytyrosol and nicotinamide has a molar ratio of hydroxytyrosol to nicotinamide of 1: 1; and a composition comprising the co-crystal of hydroxytyrosol and nicotinamide wherein the composition further comprises nicotinamide and/or a pharmaceutically acceptable excipient; and “the co-crystal of hydroxytyrosol and nicotinamide has an X-ray powder diffraction pattern showing characteristic peaks at least at 2θ angles of 11.4±0.2, 13.6±0.2, 14.9±0.2, 17.6±0.2, 18.8±0.2, 20.1±0.2, 20.3±0.2, and 20.8±0.2 degrees” as the species of the co-crystal of hydroxytyrosol and nicotinamide are maintained.
Claims 6-8 and 11-13 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on July 9, 2026, wherein claims 1, 3-5, and 9 are amended; claims 2, 6-8 and 11-13 are unchanged; claim 14 is newly added; and claim 10 is canceled.
Claims 1-9 and 11-14 are pending.
Claims 6-8 and 11-13 remain withdrawn.
Claims 1-5, 9 and 14 are under examination in accordance with the elected invention and species.
Priority
The instant application 18/548,971 filed on September 5, 2023 is a 371 of PCT/CN2022/078935 filed on March 3, 2022, which claims priority to, and the benefits of Foreign Application No.
CN202110243777.0 filed on March 5, 2021.
Action Summary
Acknowledgement is made of the receipt and entry of the amendment to the drawing filed on July 9, 2026. Applicant’s amendment to the claims and the drawings overcomes each and every objection previously set forth in the Non-Final Office Action mailed on May 11, 2026.
Claim 9 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the composition of Example 4-5, does not reasonably provide enablement for the full scope of the composition comprising the co-crystal of hydroxytyrosol and nicotinamide, wherein the composition further comprises any amount of nicotinamide and/or a pharmaceutically acceptable excipient are maintained but revisited and modified in view of the claim amendments. Specifically, the amendment deletes the recitation of “and/or a pharmaceutically acceptable excipient” and added the new limitations drawn to the molar ratio of hydroxytyrosol to nicotinamide and further incorporate “hydroxytyrosol in free form” as an alternative to nicotinamide; and therefore, the rejection of record has been reapplied, but revisited and modified in view of amendments. Claims 1-5 and 9 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement are withdrawn in view of the claim amendments.
Claim 1-5 and 9 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 are withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the composition exemplified in Example 4-5, does not reasonably provide enablement for the full scope of the composition comprising the co-crystal of hydroxytyrosol and nicotinamide, further comprising nicotinamide or hydroxytyrosol in free form, wherein the molar ratio of hydroxytyrosol to nicotinamide in the composition is 10:1 to 1:10. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims (newly reapplied as necessitated by amendment).
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary. All of the Wands factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In this case, amended claim 9 now recites “[a] composition, comprising the co-crystal of hydroxytyrosol and nicotinamide according to claim 1, further comprising nicotinamide or hydroxytyrosol in free form, wherein the molar ratio of hydroxytyrosol to nicotinamide in the composition is 10:1 to 1:10”, in which claim 1 is specifically drawn to “[a] co-crystal of hydroxytyrosol and nicotinamide, wherein the co-crystal of hydroxytyrosol and nicotinamide has a molar ratio of hydroxytyrosol to nicotinamide of 1:1, and wherein the co-crystal of hydroxytyrosol and nicotinamide has an X-ray powder diffraction pattern showing characteristic peaks at 2θ angles of 11.4±0.2, 13.6±0.2, 14.9±0.2, 17.6±0.2, 18.8±0.2, 20.1±0.2, 20.3±0.2, and 20.8±0.2 degrees”.
In short, the breadth of the claims does not arise merely from combing the co-crystal with any excess amount of nicotinamide or hydroxytyrosol in free form; Rather, the claims permit independent selection of either nicotinamide or hydroxytyrosol in free form and combine it with the cocrystal to arrive at a specific molar ratio of hydroxytyrosol to nicotinamide in the composition in the range of 10:1 to 1:10; and that encompass numerous potential composition(s) with a broad molar ratio range and any additional, unrecited elements. The disclosed examples do not proportionately sample that broad composition genus; Instead, the examples cluster around a molar ratio of hydroxytyrosol to nicotinamide of 1:2 and 1:3 in the composition as a raw material to prepare composition containing the cocrystal and excess amount of “free nicotinamide crystal”.
The claimed invention pertains to compositions that contain the co-crystal plus excess amount of nicotinamide or hydroxytyrosol in free form, which is obtained during the process of preparing the co-crystal that has a 1:1 molar ratio. While the composition may be obtained during the process of preparing the claimed co-crystal, but the claimed invention is not limited to just the composition obtained during the process of preparing the claimed cocrystal. Rather, the claim permits the incorporation of any excess amount of free form of nicotinamide or hydroxytyrosol in combination with the claimed co-crystal to arrive at a variety of compositions comprising hydroxytyrosol and nicotinamide in the molar ratio instantly claimed. The nature of the invention requires the co-crystal contains therein to retain its crystalline characteristic(s) when the excess amount of free form of nicotinamide or hydroxytyrosol is present, rather than merely combining or mixing the two components together that satisfy the claimed genus.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
According to Tim (Journal of Chemical and Pharmaceutical Research, 2024, 16(5): 9-10), one skilled in the art would have known that polymorphs significantly affect solubility, dissolution rate, stability, and bioavailability; different polymorphs of the same compound can exhibit different pharmaceutical behavior, despite identical chemical composition (see e.g., p. 9, 1st paragraph). One skilled in the art would have also known that polymorphs forms are sensitive to formulation conditions, including excipients selection, processing conditions, and storage; Polymorphs may undergo phase transitions, recrystallization, and conversion to less stable forms during storage or manufacturing processes (see e.g., p. 9, 2nd paragraph and p. 10, 2nd paragraph). In other words, the crystal polymorph in the composition is highly sensitive to formulation variables. While the level of skilled in the art with respect to forming a composition would have been high, there is lack of predictability surrounding polymorph behavior in manufacturing the claimed genus of compositions.
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all the foregoing, at the time the application was filed, it would have required undue experimentation to practice the entire scope of the claimed invention. In this case, the instant specification provides two species of composition (Example 4 and Example 5) as depicted below (see page 10-11 of the specification):
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. In short, although the specification provide guidance to prepare the compositions containing the claimed co-crystal of hydroxytyrosol and nicotinamide and “free nicotinamide crystal”, which is obtained during the process of preparing the claimed cocrystal using a raw material composed of hydroxytyrosol and nicotinamide with a molar ratio of 1:2 and 1:3, respectively, the disclosure fails to teach how to formulate the full scope of the claimed composition genus with broad molar ratio while maintaining the claimed cocrystal in the presence of extra hydroxytyrosol or nicotinamide in free form. It is respectfully noted that the disclosure compares the chemical stability of the claimed co-crystal with the compositions obtained in Example 4-5 at 40°C/75% RH in Example 7, and describes “the content of hydroxytyrosol was slightly decreased in the composition comprising the co-crystal of hydroxytyrosol and nicotinamide” after 30 days, which indicates the compositions comprising excess amount of nicotinamide in free forms alters the chemical stability when compared to the co-cystal form alone.
In addition, the specification does not provide any examples drawn to preparing compositions comprising an excess amount of hydroxytyrosol in free form, and at the same time, it discloses that hydroxytyrosol has the defect of low melting point and poor stability (see e.g., p. 5, line 27 to p. 6, line 3). In view of the unpredictability of pharmaceutical cocrystal behavior during formulation, one skilled in the art armed with general knowledge cannot reasonably determine whether adding any excess amount of hydroxytyrosol in free form, which has low melting point and poor stability, can successfully preserve the claimed cocrystal without undue experimentation.
In this case, the breadth of the claim is substantial, the specification only provides limited examples for obtaining compositions comprising the cocrystal with excess amount of free nicotinamide crystal using a specific molar ratio of raw material. Based on the limited disclosure provided and ordinary knowledge alone, one skilled in the art could not reasonably predict what other amount of nicotinamide or hydroxytyrosol in free form can be incorporated without altering the polymorph behavior of the co-crystal of hydroxytyrosol and nicotinamide contains within the composition. Therefore, the quantity of experimentation necessary to practice the entire scope of the claimed invention is high, because it would require extensive formulation screening across the untested portion of the genus to identify the amount of nicotinamide or hydroxytyrosol in free form and formulation conditions that can preserve the claimed cocrystal throughout the full scope of the claim; and at the same time, ensuring the process can arrive at stable and effective compositions when changing the overall molar ratio. Given the sensitivity of polymorphic forms to formulation conditions and the lack of guidance in the specification, a person of ordinary skill in the art would be required to engage in undue experimentation to practice the full scope of the composition instantly claimed in view of the unpredictability of cocrystal behavior during formulation.
Accordingly, while the specification supports the composition of Example 4-5, the entire scope of composition instantly claimed is not enabled by the instant specification. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Response to Arguments
Applicant's arguments filed on July 9, 2026 have been fully considered.
Applicant's arguments filed on July 9, 2026 with respect to the rejection of Claim 9 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the composition of Example 4-5, does not reasonably provide enablement for the full scope of the composition have been fully considered but they are not persuasive.
In this case, applicant amends claim 9 by deleting the recitation of “and/or a pharmaceutically acceptable excipient” and amends the scope of the claim by further adding the limitation of “or hydroxytyrosol in free form” and the limitation of “wherein the molar ratio of hydroxytyrosol to nicotinamide in the composition is 10:1 to 1:10”. Each of these findings demonstrates that the amendment changes the scope of the claims.
In Summary, applicant argues that the claim amendment overcomes the rejection of record.
In response, applicant’s arguments are not found persuasive. While applicant deletes the recitation of “and/or a pharmaceutically acceptable excipient” from the claim language and added new limitations, the breath of the amended claim still encompasses a broad composition genus encompassing a broad molar ratio range of hydroxytyrosol to nicotinamide, and that contains the claimed cocrystal, various amount of nicotinamide or hydroxytyrosol in free form, and any additional, unrecited elements. As noted in the rejection set forth above, one skill in the art would have known that the polymorphs are sensitive to formulation conditions, which is also evidenced by the disclosure of instant specification. Because the specification only provides generalized guidance to prepare the claimed composition and does not teach how to formulate the full scope of the claimed compositions without loss of the claimed cocrystal, the specification does not enable the full scope of composition genus without undue experimentation for the reason set forth herein.
Therefore, the previous rejection has been withdrawn, but has been reapplied, revisited and modified as necessitated by amendment that changes the scope of the claims.
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 9 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 (newly applied as necessitated by amendments).
Regarding claim 9, the limitation that recites “the molar ratio of hydroxytyrosol to nicotinamide in the composition is 10:1 to 1:10” renders the claim indefinite, because it is unclear which hydroxytyrosol and nicotinamide referred to therein is used to calculate the molar range. Specifically, the instant claim is drawn to composition comprising two components, one is drawn to the co-crystal of hydroxytyrosol and nicotinamide while the other one is drawn to free form of nicotinamide or hydroxytyrosol. For instance, to the extent that that the second component is free form of nicotinamide, is the “nicotinamide” in the phrase of “the molar ratio of hydroxytyrosol to nicotinamide” referring to (i) moles of nicotinamide in the cocrystal plus the moles of nicotinamide in free form, or (ii) referring to just the mole of nicotinamide in free form? Same logic applies to hydroxytyrosol. Therefore, the claims are considered indefinite because it is not clear which interpretation applies, and one cannot reasonably determine the metes and bounds of the claimed composition.
Free of the Art
Claims 1-5, 9 and 14 are free of the art.
Conclusion
Claims 1-5 and 14 are allowable; and claim 9 is not allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
