DETAILED ACTION
This office action is in response to applicant’s filling dated May 22, 2026.
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
Claims 1, 3, and 5-10 are pending in the instant application. Acknowledgement is made of applicant’s remarks and amendments filed May 22, 2026. Acknowledgement is made of applicant’s cancellation of claims 2, 4, and 11.
Priority
The present application is a 371 of PCT/EP2021/072808 filed on August 17, 2021 which claims benefit of foreign priority to EP20191343.1 filed on August 17, 2020.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
New Rejections
Necessitated by Claim Amendment
Claim Rejections - 35 USC § 112(b)
Indefinite
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, 3, and 5-10 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation a crystal form of 5-bromo-6-chloro-3-indoxyl caprylate characterized by an X ray powder diffraction pattern comprising one or more peaks selected from 5.5376, 11.0389, and 16.7875 Degrees 2 theta, and the claim also recites a crystal form of 5-bromo-6-chloro-3-indoxyl caprylate as shown in Fig. 1 which is the narrower statement of the range/limitation. In addition, claim 3 recites the broad recitation a crystal form of 5-bromo-6-chloro-3-indoxyl caprylate characterized by an X ray powder diffraction pattern comprising one or more peaks selected from 6.5175, 6.6308, and 11.5021 Degrees 2 theta, and the claim also recites a crystal form of 5-bromo-6-chloro-3-indoxyl caprylate as shown in Fig.2 which is the narrower statement of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 5-10, which depend from claim 1, do not clarify the ambiguity of claim 1. Thus, the rejection also applies to claims 5-10.
Claim Rejections - 35 USC § 112(a)
Written Description
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 1, 3, and 5-10 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 claims contain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. For instance, fewer species will be required where the skill and knowledge in the art is high, and more species will be required when the claimed genus is highly variable.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
(1) Partial structure:
Claim 1 is directed to a crystalline form of bromo-6-chloro-3-indoxyl caprylate characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 5.5376, 11.0389, and 16.7875 2Th. Claim 3 is directed to a crystalline form of bromo-6-chloro-3-indoxyl caprylate characterized by an X-ray powder diffraction pattern comprising one or more peaks selected from 6.5175, 6.6308, and 11.0521. Instant claims 5 and 8 are directed to a method of making a crystalline form claims 1 and 3, respectively. Instant claims 6 and 7 are directed to a system and a method for detecting presence or absence of an esterase comprising the crystalline form of claim 1. Instant claims 9 and 10 are directed to a system and a method for detecting presence or absence of an esterase comprising the crystalline form of claim 3. The scope of claims 1 and 3-10 encompass ALL pluralities of bromo-6-chloro-3-indoxyl caprylate crystalline polymorph which exhibits an x-ray powder diffraction pattern having a characteristic peak in one of 5.5376, 11.0389, 16.7875, 6.5175, 6.6308, or 11.0521 2TH.
A review of the XRPD spectrum in Figure 1 (corresponding to the claimed bromo-6-chloro-3-indoxyl caprylate of claim 1) and Figure 2 (corresponding to the claimed bromo-6-chloro-3-indoxyl caprylate of claim 3) fails to pick and label ANY distinguishing x-ray diffraction peaks or non-distinguishing peaks. However, the Applicant has disclosed 2 polymorphic species which exhibits a characteristic peak in degrees 2-theta at approximately 11.03. As shown in Table 1 [0049] and Table 2 [0051], the polymorphic species in Figure 1 and 2 of the instant specification exhibit more than 30 characteristic peaks. However, in a review of Figure 3, Fig. 1 and 2 correspond to very different crystalline structures.
(2) Physical properties
Claims 1, 3, and 5-10 disclose limited physical properties directed to the two specific claimed polymorphic forms of bromo-6-chloro-3-indoxyl caprylate. Said claims do not discuss other physical properties for the structural elucidation of polymorphic forms and distinction from other polymorphic forms, specifically, distinct peak locations in the XRPD spectrum. The claims merely recite a limitation directed to a crystalline structure having at least one of the claimed peaks, a process of making a crystalline form having an x-ray powder diffraction pattern having at least one of claimed peaks, a system or method for detecting an esterase comprising a crystalline form an x-ray powder diffraction pattern having at least one of claimed peaks.
It has been established in the art that the identification of two peaks (and in the instant case, one peak) in an X-ray powder diffraction (XRPD) spectrum is insufficient to identify a specific crystalline form. “Since every compound produces its own characteristic powder pattern owing to the unique crystallography of its structure, powder x-ray diffraction is clearly the most powerful and fundamental tool for a specification of the polymorphic identity of an analyte” (Brittain et al. "Polymorphism in Pharmaceutical Dosage Forms." Polymorphism in Pharmaceutical Solids XX (January 1999) pp.235-238). However, Brittain also explains that proper identification of a particular crystal structure is established by looking at the margin of error of the ten strongest reflections (i.e. peaks) for an analyte material in comparison with a reference material, and further that identity is only established when the scattering angles are within 0.2 degrees and the intensity of the reflections do not vary by more than 20 percent (p.236, paragraph 2, lines 10-18). Thus, the reference clearly makes the case that properly identifying a particular crystalline structure requires the identification of its ten strongest reflections, which are not present within the scope of claims 1, 3, and 5-10.
(3) Method of making the claimed invention:
Methods of synthesizing bromo-6-chloro-3-indoxyl caprylate are, in general, known to the skilled artisan. However, a method of making a distinct species bromo-6-chloro-3-indoxyl caprylate “which exhibits an x-ray powder diffraction pattern having a characteristic peak in at least one of the claimed peaks is beyond the skill of the artisan as, the state of the prior art discloses that forming polymorphic forms of a compound is unpredictable.
Vippagunta et al (Crystalline Solids: Advanced Drug Delivery Reviews Vol. 48 pages 3-26 published 2001) is brought in to teach the state of the prior art on the unpredictability of distinct polymorph formation of a specific compound: "The main challenge in managing the phenomenon of multiple solid forms of a drug is the inability to predict the number of forms that one can be expected in a given case. This prediction would involve quantification of the myriad intermolecular forces within any proposed crystal structure as well as the ability to postulate the likely packing modes for a given molecule in all its configurations" (page 11, right col. paragraph 3).
As described in MPEP § 2163, for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. In the instant case, the genus of bromo-6-chloro-3-indoxyl caprylate polymorphs comprise a substantial variance in the plurality of distinguishing peaks between 5-30 degrees 2theta. Considering that preparation of specific polymorphic forms of a specific compound with distinct XRPD is unpredictable as taught by Vippagunta et al, it is unquestionable that the claims are broad and generic, with respect to all possible and unpredictable polymorphic forms of bromo-6-chloro-3-indoxyl caprylate with the claimed melting points and characteristic peaks. The possible variations are limitless. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. Moreover, as stated above, the specification lacks sufficient variety of species to reflect this variance in the genus. Thus, the specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
Claims 1, 3, and 5-10 are rejected. No claim is allowed.
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.
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/A.R.U./Examiner, Art Unit 1628
/Rayna Rodriguez/Primary Examiner, Art Unit 1628
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