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 December 12, 2024 are acknowledged and entered. Claims 134 and 136-162 are pending.
Priority
This application is a DIV of 18/051,471, filed October 31, 2022, now US 12,102,625, which is a DIV of 16/791,974, filed February 14, 2020, now US 11,524,005, which claims benefit of 62/807,542, filed February 19, 2019.
Information Disclosure Statement
Acknowledgement is made of the Information Disclosure Statement filed on December 16, 2024. 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.
Claim Rejections - 35 USC § 112a
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 134 and 136-160 are 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 a method of treating congenital hepatic fibrosis, does not reasonably provide enablement for preventing congenital hepatic fibrosis.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In the instant case, the claims are drawn to a method of treatment or prevention of disease. Applicant teaches that the instant compound is an agonist or modulator of FXR (see [0003]); however, this activity is not known to be correlated with the prevention of any disease. Applicant’s disclosure is only enabling for the treatment or prevention of conditions which Applicant has demonstrated may be treated or prevented by the instant compound, and of conditions which the prior art is already aware may be treated or prevented by a compound with the disclosed activity and for which Applicant has written support. Case law is clear on this point. In an unpredictable art, such as drug therapy to treat disease, models may be used for enablement only if there is a reasonable correlation between the activity in question and the asserted utility. Given the guidance provided by Applicant, one skilled in the art would not be able to practice the full scope of the invention without undue experimentation.
In evaluating the enablement question, several factors are to be considered. Note In re Wands, 8 USPQ2d 1400 and Ex parte Forman, 230 USPQ 546. The factors include: 1) The nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the breadth of the claims, and 7) the quantity of experimentation needed. The determination that “undue experimentation” would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations.
Nature of the Invention and Breath of the Claims
Instant claim 134 is drawn to a method of treating or preventing a disease or condition in a patient in need thereof, comprising administering a therapeutically effective amount of an FXR agonist, wherein the disease or condition is congenital hepatic fibrosis, and wherein the FXR agonist comprises a solid form of a compound of formula
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Instant claims 136-160 depend from claim 134 and include the limitation “preventing”.
“Preventing” as defined in the specification (see [0094]) means any treatment of a disease or condition that causes the clinical symptoms of the disease or condition not to develop.
The nature of the invention is thus a method of treating or preventing congenital hepatic fibrosis comprising administration of an FXR agonist or modulator. The scope of the method is understood to include wherein the method causes the clinical symptoms of the disease or condition not to develop.
The state of the prior art
State of the prior art reference Guerra et al. (Arq Gastroenterol 2018, 55(4), Abstract) teaches congenital hepatic fibrosis is a genetic disease (Abstract; Congenital hepatic fibrosis is an autosomal recessive disease due to mutation…). The state of the art is not aware of any therapeutic agent that prevents this condition.
The Level of One of Ordinary Skill
The level of skill in the art is high. The artisan using the claimed invention would be a person with medical training such as a medical doctor or physician with an MD degree or the equivalent.
Predictability in the art
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Amount of guidance/working examples
No experimental or other data is provided to show the instant compound prevents the claimed disease. Moreover, there is no evidence in the record to suggest the claimed invention prevents any condition claimed. It is presumed “prevention” of the claimed disease would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. Nothing in the specification teaches how one skilled in the art identifies a subject who’s disease will be prevented.
The quantity of experimentation needed:
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on theevidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here and one skilled in the art could not practice the full scope of the claimed invention without undue experimentation.
This rejection could be overcome by amending the claims to delete “preventing”.
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.
Claims 134 and 136-160 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. The claims are indefinite for the reasons that follow:
In claim 134, the phrase “FXR agonist comprises” renders the claim indefinite because it is unclear what other structural elements are regarded as part of an FXR agonist other than the formula recited in the claim. Applicant teaches “comprises” is to be construed in an open, inclusive sense, that is as “including but not limited to” (see [0083]). In this case, the term “comprises” renders structure of the FXR agonist itself is ambiguous because one skilled in the art could not say what other elements are included. It is suggested the claim be amended to replace “comprises” with “is”, e.g. “FXR agonist is”.
Claims 136-160 depend from claim 134, include the limitation “FXR agonist comprises”, and are therefore also indefinite.
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 136-137, 139-141, 143-144, 146-147, 149-150, 152-156 and 158-159 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.
Claims 136-137, 139-141, 143-144, 146-147, 149-150, 152-156 and 158-159 are substantial duplicates of claim 134. Each of these claims depends from claim 134 and recites wherein each of the crystalline forms recited in claim 134 is characterized by an X-ray diffraction pattern further comprising additional peaks (2ɵ reflections). One skilled in the art would understand that these claims are doing no more than reciting additional peaks which are properties that are inherent the crystalline forms recited in claim 134. Thus, claims 136-137, 139-141, 143-144, 146-147, 149-150, 152-156 and 158-159 are not teaching a new or different crystalline form of claim 134, rather they just adding additional peaks which only adds more detail to the claim. The crystalline forms which are present in claim 134 are identical to the crystalline forms in dependent claims 136-137, 139-141, 143-144, 146-147, 149-150, 152-156 and 158-159. The claims are thus rejected for failing to further limit the subject matter of the claim upon which they depend.
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.
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 134 and 136-160 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-36 of U.S. Patent No. 11,524,005 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the patent claims.
MPEP 804.01 states the prohibition against nonstatutory double patenting rejections under 35 U.S.C. 121 does not apply when (B) The claims of the application under examination and claims of the other application/patent are not consonant with the restriction requirement made by the examiner, since the claims have been changed in material respects from the claims at the time the requirement was made. For example, the divisional application filed includes additional claims not consonant in scope with the original claims subject to restriction in the parent. Symbol Technologies, Inc. v. Opticon, Inc., 935 F.2d 1569, 19 USPQ2d 1241 (Fed. Cir. 1991); Gerber Garment Technology, Inc. v. Lectra Systems, Inc., 916 F.2d 683, 16 USPQ2d 1436 (Fed. Cir. 1990). In order for consonance to exist, the line of demarcation between the independent and distinct inventions identified by the examiner in the requirement for restriction must be maintained. 916 F.2d at 688, 16 USPQ2d at 1440. In the present case, the instant claims are not consonant with the restriction requirement made by the examiner in Application No. 16/791,974 because the claims have been changed in material respects from the claims at the time the requirement was made.
The patent claims are drawn to a solid form tromethamine salt of a compound , having
the following formula
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The crystalline solid forms of the patent claims include those recited in the instant claims (e.g. see patent claim 1: the solid form is tromethamine salt Form I characterized by an X - ray diffraction pattern having 2ɵ - reflections at 5.2 , 16.8 , and 25.6 degrees 2ɵ , plus or minus 0.2 degrees 2ɵ)
The patent specification teaches the solid form has use in treating congenital hepatic fibrosis (col 30). In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See also Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008);Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
The difference between the patent claims and the instant claims is that the instant claims are drawn to a method of treating congenital hepatic fibrosis. However, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to use the patented compound in a method of treating congenital hepatic fibrosis as is claimed because the compound had this reported utility.
One would have been motivated as a matter of practicing the patented invention.
One would have had a reasonable expectation of success because the patent disclosed that the compound was useful for the treatment of congenital hepatic fibrosis.
Claims 161-162 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-36 of U.S. Patent No. 11,524,005 B2 in view of Jones (Drug Discovery Series, CH 1 Preformulation Studies, 2018, pages 1-20)(hereinafter “Jones”).
The patent claims are drawn to a solid form tromethamine salt of a compound , having
the following formula
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The crystalline solid forms of the patent claims include those recited in the instant claims (e.g. see patent claim 1: the solid form is tromethamine salt Form I characterized by an X - ray diffraction pattern having 2ɵ - reflections at 5.2 , 16.8 , and 25.6 degrees 2ɵ , plus or minus 0.2 degrees 2ɵ).
The patent specification teaches the solid form has use in treating congenital hepatic fibrosis (col 30).
The patent claims are silent regarding a pharmaceutical composition; however, Jones teaches that during the development of a new medical product the candidate drug should be formulated into a dosage for the appropriate study (page 1). Jones teaches pre-formulation studies should be conducted to evaluate excipients and their interaction with drug substances (page 2, Figs 1.1 and 1.2).
The difference between the patent claims and the instant claims is that the instant claims are drawn to a pharmaceutical composition. However, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the patented invention into a pharmaceutical composition because the patented compound had medicinal use in the treatment of congenital hepatic fibrosis, at the time it was known that candidate drugs should be formulated for evaluation, and the result of such formulation would have been a composition.
One would have been motivated as a matter of investigating the treatment of congenital hepatic fibrosis with the patented compound.
One would have had a reasonable expectation of success because at the time it was known that candidate drugs required formulation.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEVIN MARTIN whose telephone number is (571)270-0917. The examiner can normally be reached Monday - Friday 8 am - 5 pm.
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August 26, 2026
/K.S.M./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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