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 without traverse of Group II, encompassed by claims 2-10, drawn to a crystalline form of 25HC3S choline, in the reply filed on 04/10/2026 is acknowledged.
Applicant has not pointed to any errors in Examiner’s analysis of the different inventions. The requirement is still deemed proper and is therefore made FINAL.
In the Response to Restriction Requirement as filed on 4/10/2026, applicant has amended no claims; cancelled no claims; and added no new claims. Claims 1, 101-109, and 112 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Therefore, claims 1-10, 101-109, and 112 are currently pending and claims 2-10 are under consideration.
Priority
The instant application is 35 U.S.C. § 371 International Application of PCT/US2022/034959, filed June 24, 2022, which claims the benefit of the provisional application 63/215,383, filed June 25, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 9/4/2024 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
The information disclosure statement filed on 1/17/2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because:
37 CFR 1.98(a)(2) requires a legible copy of each cited foreign patent document. Currently, the three foreign documents on the IDS filed on 1/17/2025 are missing document text and only show images.
37 CFR 1.98(a)(2) requires a legible copy of each cited non-patent literature publication or that portion which caused it to be listed. Currently, the “Flamm et al.” and “Goel et al.” poster presentations are not legible.
The above documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
The applicant has an obligation to call the most pertinent prior art to the attention of the U.S. Patent and Trademark Office in a proper fashion. Burying one reference in one hundred other IDS references is like citing nothing. PENN YAN BOATS, INC. v. SEA LARK BOATS, INC. 175 USPQ 260 (S.D. Fla. 1972). Golden Valley Microwave Foods, Inc. v. Weaver Popcorn Co. Inc., 24 USPQ2d 1801 (U.S. Dist. N. Dist. IN 1992).
Specification
Acknowledgement is made of the drawings received 12/20/2023. These drawings are acceptable.
The inventor or joint inventor is reminded of the proper contents of the specification, that must include:
(b) CROSS-REFERENCES TO RELATED APPLICATIONS: See 37 CFR 1.78 and MPEP § 211 et seq.
The disclosure is objected to because of the following informalities: it lacks part (b): CROSS-REFERENCES TO RELATED APPLICATIONS. Appropriate correction is required.
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.
Claim Rejections - 35 USC § 112(a)
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.
Claims 3-10 are 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The following claims fail to meet the written description requirement with regards to identifying the specific crystalline form of 25HC3S choline.
The x-ray pattern of a pure crystalline substance can be used to identify compounds because the diffraction pattern is considered to be a "fingerprint" of a compound. The d value for the most intense line is found and compared, followed by the next two intense lines, and so on.
Identification of crystal structures is taught by Bhattacharya et al. (Brittain, ed. Polymorphism in Pharmaceutical Solids, 2009, page 334). As noted in the fourth full paragraph, "it is usually convenient to identify the angles of the 10 most intense scattering peaks in a powder pattern" or the last paragraph which states 5 characteristic XRD (X-Ray Diffraction) scattering peaks of sodium ibandronate was sufficient to determine the difference in the two polymorphic forms.
Thus, only one peak cannot be used to identify an unknown compound.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Ren et al. (US 2013/0143854 A1, published 02/14/2013, cited on IDS filed XX)(hereinafter, ‘Ren’) in view of Feinstone et al. (US 2,928,848, published 3/15/1960, cited on IDS filed XX)(hereinafter, ‘Feinstone’) and Berge et al. (J. Pharm. Sci., 1977, 66, 1-19)(hereinafter, ‘Berge’).
Ren teaches (para [0011]) the following compound, 5-cholesten-3β, 25-diol 3-sulphate (25HC3S):
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Ren further teaches 25HC3S can be formulated in various types of salts (para [0058]), reciting “the compounds may be administered in the pure form or in a pharmaceutically acceptable formulation including suitable elixirs, binders, and the like (generally referred to as “carriers”) or as pharmaceutically acceptable salts (e.g. alkali metal salts such as sodium, potassium, calcium or lithium salts, ammonium, etc.) or other complexes" (emphasis added).
Ren does not teach crystalline 25HC3S choline.
Feinstone teaches (col 1, lines 46-49) a choline salt of a crystalline steroid compound (shown below), reciting “these compounds may be considered as choline salts of the acid sulfate of a steroid compound in which the sulfate is attached to an enolic carbon atom in the 7 position".
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Feinstone further discloses (col 1, lines 62-68) that choline estrone sulfate is relatively stable and useful for oral administration, reciting “choline estrone sulfate is a crystalline material which melts with decomposition at 255-8oC., and is readily soluble in water, as contrasted with estrone, which is insoluble in water. It has been found to be physiologically active when administered orally and is quite stable", and (col 1, lines 24-26), "sodium estrone sulfate prepared from synthetic estrone is known to be unstable and therefore has not found practical medical use".
Berge teaches choline as an FDA-approved commercially marketed salt (page 2, Table 1, “Cation”).
The primary reference teaches the base compound, which can be prepared with any organic acid. The specific acid of the claims is not named in the primary reference. Thus, the difference between the claims and the prior art is that applicants have prepared a novel crystalline salt of an old drug. Berge teaches the choline salt and Feinstone teaches the crystalline choline salt of a sulfated C7 steroid.
When the exact compound is not specifically named, but instead it is necessary to select portions of teachings within a reference and combine them, e.g., select various substituents from a list of alternatives given for placement at specific sites on a generic chemical formula to arrive at a specific composition, anticipation can only be found if the classes of substituents are sufficiently limited or well delineated. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). If one of ordinary skill in the art is able to “at once envisage” the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be “at once envisaged.”
The factual situation is thus largely the same as in Pfizer, Inc. v. Apotex, Inc. 82 USPQ2d 1321 which was directed to the amlodipine besylate drug. At the time of the invention, amlodipine was known as was the use of besylate anions. While the amlodipine besylate had the same therapeutic use, Pfizer discovered that the besylate (benzene sulphonate) form had superior properties. Pfizer’s argument that the results of forming amlodipine besylate would have been unpredictable, and therefore were nonobvious, was unpersuasive. The court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties (e.g., non-stickiness, and improved stability) while at the same time having good solubility, and non-hygroscopicity. The court found that one of ordinary skill in the art looking to improve amlodipine would have looked to forming a salt of the compound with the group of potential salt-formers being a group of 53 anions already known to form pharmaceutically acceptable salts, which would be an acceptable number to provide ‘‘a reasonable expectation of success.’’ Indeed, the Court decision quoted unrefuted testimony that “part and parcel of pharmaceutically accepted[] was to look in pharmacopoeias and compendia” to find an anion having “precedence for use within the pharmaceutical industry” and that it “It would be logical to try” salts from the known list (page 1331). That other drugs which used the besylate salt did not have the same therapeutic use as amlodipine was called “unimportant, if not actually irrelevant” (page 1332). The Court further noted that “upon making a new acid addition salt, it was routine in the art to verify the expected physicochemical characteristics of each salt”, so that if “one skilled in the art would have had a reasonable expectation of success at the time the invention was made” one “merely had to verify that expectation” and learn of these properties (page 1335). Moreover, the Court found this “analogous to the optimization of a range or other variable within the claims that flows from the “normal desire of scientists or artisans to improve upon what is already generally known.” In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)…”
Accordingly, the secondary references provide a “reasonable expectation of success”, and that is all the law requires, not a total predictability. See In re Clinton, 188 USPQ 365; In re Longi, 225 USPQ 645, 651; Alza Corp. v. Mylan Laboratories Inc., 80 USPQ2d 1001, 1006; In re Corkill, 771 F.2d 1496, 1500 ; Brown & Williamson Tobacco Corp. v. Philip Morris Inc., 56 USPQ2d 1456; Merck & Co., Inc. v. Biocraft Labs., Inc., 10 USPQ2d 1843; In re Merck & Co., Inc., 231 USPQ 375; In re Rinehart, 189 USPQ 143; In re O'Farrell, 7 USPQ2d 1673.
It would be obvious to of one of ordinary skill in the art to make 25HC3S choline in view of Berge because choline is one of the specific salts taught in the secondary reference. It would have been obvious to formulate crystalline 25HC3S choline by routine experimentation, in order to find the most effective crystalline 25HC3S salt form for the inflammation treatment because Feinstone teaches crystalline choline salts of sulfated C7 steroids. Thus, claim 2 is obvious over Ren.
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.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 3, 10, and 13 of copending Application No. 19/142,096 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 2 is drawn to the crystalline form of 25HC3S choline. Reference claim 3 is drawn to “a crystalline salt of 25HC3S other than a crystalline sodium salt of 25HC3S”. The choline salt of instant claim 2 is not a sodium salt, and therefore, reference claim 3 is directed to an invention embraced by the present claims. Reference application further recites (para 00135): “the amine salts are amine alcohol salts of 25HC3S including choline, hydroxyethylammonium, hydroxyethylpyrrolidinium, meglumine, tromethammonium, and diethanolamine” (emphasis added) and recites, in Table 19 (page 68-69), the peaks of crystalline 25HC3S choline.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1, 14, and 16 of copending Application No. 19/142,082 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 2 is drawn to the crystalline form of 25HC3S choline. Reference claims 1, 14, and 16 specifically recite different solid 25HC3S choline forms (e.g. composition, amorphous, micronized. The ‘crystalline’ nature of the compound is an inherent characteristic and therefore included in the teachings of the reference.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
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/L.A.B./Examiner, Art Unit 1624
/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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