DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission, filed 01/16/2026, has been entered.
Status of Application
Receipt of the amendments to the specification and claims as well as applicant arguments/remarks, filed 01/16/2026, is acknowledged. Amendments to the specification have been entered.
Claims 1, 4-7, 9-12, 14-18, 24-28 are pending in this action. Claims 2, 3 have been cancelled. Claims 8, 13, 19-23 have been cancelled previously. Claims 1, 5-7, 9, 12, 14, 16-18, 24-25 have been amended. New claims 26-28 have been added. No new matter was added. Claims 1-7, 9-12, 14-18, 24-28 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant's amendments necessitated new ground(s) of rejection presented in this office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/EP2021/052163, filed January 29, 2021, which claims benefit of foreign priority to EP20306410.0, filed November 19, 2020, and EP20305089.3, filed January 31, 2020.
Specification
The lengthy specification (106 pages as filed 07/23/2025, exclusive of claims) 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 errors of which applicant may become aware in the specification. MPEP 608.01. The specification is objected to because of the following informalities:
As stated previously, the specification comprises references on a publication(s) (e.g., Page 56). The publications recited in the instant application should be identified by publisher, author (if any), title, relevant pages of the publication, date, and place of publication. MPEP 609.05(a). Regarding electronic document(s) retrieved from an online source, it is noted that the format for the citation of an electronic document should be similar to the format used for paper documents of the same type, with the addition of the information in the locations (internet, database, etc.) indicated. MPEP 707.05(e). Appropriate correction is required.
Information Disclosure Statement
The information disclosure statement, filed 11/12/2025, is acknowledged and has been considered. Please see the attached initialed PTO-1449 forms.
Claim Objections
Claims 7, 10, 26-28 are objected to because of the following informalities:
Claim 7 comprises the typographic error “is in a range of from 30% to 95%” that needs to be corrected to “is in the range of from 30% to 95%”. Similar is applied to claim 26.
In claim 10 (dependent on claim 9) the term “monoalcohol” should be corrected to “alcohol” or clarified (see claim 9).
Claim 27 comprises the typographic error “is in an amount of 35%” that needs to be corrected to “is in the amount of 35%” or clarified. Similar is applied to claim 28.
Appropriate correction is required.
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 1, 4-7, 9-12, 14-18, 24-28 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 enablement requirement.
The claim(s) contains subject matter, which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirement, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are (see MPEP 2164.01(a)): (1) scope or breadth of the claims; (2) nature of the invention; (3) relative level of skill possessed by one of ordinary skill in the art; (4) state of, or the amount of knowledge in, the prior art; (5) level or degree of predictability, or a lack thereof, in the art; (6) amount of guidance or direction provided by the inventor; (7) presence or absence of working examples; and (8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. MPEP 2164.01(a). In the present case,
(1) The claims disclose an amorphous solid dispersion(s) comprising 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier selected from povidone, copovidone, hydroxypropylmethylcellulose acetate succinate, methacrylic acid/ethyl acrylate copolymers, a mixture of povidone and copovidone, a mixture of copovidone and citric acid, a mixture of copovidone and polysorbate 80, a mixture of copovidone and hydroxypropylmethylcellulose acetate succinate, and a mixture of povidone and citric acid (claim 1); wherein said amorphous solid dispersions are prepared by (i) dissolving 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or salt thereof in a solvent(s) to obtain a solution; and (ii) by adding to said solution the at least one pharmaceutically acceptable carrier (claim 9); and wherein said amorphous solid dispersions can be incorporated into pharmaceutical compositions comprising pharmaceutically acceptable excipient(s) (claim 16) to be used for treatment inflammatory diseases (claims 18, 24).
(2) The nature of the invention is directed to amorphous solid dispersions (ASD) comprising 8-chloro-N-(4- (trifluoromethoxy)phenyl)quinolin-2-amine or a pharmaceutically acceptable salt thereof (as an active agent) and at least one pharmaceutically acceptable carrier to be incorporated into pharmaceutical compositions for treatment and prevention of various diseases.
(3) The relative level of skill possessed by one of ordinary skill in the art of biomedical research, polymer science, physical chemistry, and/or biochemical engineering is relatively high, as a majority of lead investigators directing scientific research and development in this particular technological area possess a Ph.D. or M.D. in a scientific discipline such as biochemistry, physical chemistry, molecular biology, bioengineering, pharmacology, medicine, medicinal chemistry, polymer science, material engineering, biology or the like.
(4) State of the art of medical/pharmacological research comprises laborious time-consuming and costly experimental methods comprising preparation of perspective compounds/compositions, functional and non-functional assays for perspective combinations, representing both in vitro and in vivo experiments, where it is nearly impossible to test large quantities of compositions/combinations in vivo. In the present case, one would need to (i) identify effective compositions and/or amounts of actives and carriers for providing an ADS; (ii) identify compounds/additives that can be used and/or should be excluded from pharmaceutical formulations comprising said ADS; (iii) optimize doses and/or schedule of treatment for patients with different conditions; (iv) identify the potential negative side effects caused by the treatments.
(5) Level or degree of predictability, or a lack thereof, in the art. In the present case, it is noted that the instant specification teaches that ASD means a glass solution, wherein the active pharmaceutical ingredient is under an amorphous form, and the pharmaceutically acceptable carrier is also under an amorphous form in which said active pharmaceutical ingredient molecules (the solute molecules) are dispersed molecularly, and wherein said glass solution forms is a homogeneous one-phase system (Specification, Page 7). To this end, it is noted that it is well known in the field that level or degree of predictability of physical properties of multicomponent systems/compositions is low, given that said properties depend on compounds included as well as on concentrations thereof that define network of inter- and intramolecular interactions, and thereby, physical and chemical properties of said systems/compositions. Therefore, not only chemical structure of selected compounds/active ingredients define “structure-function relationship”, but also entire structure of the formulations may impact the structure of the compositions (i.e., amorphous) and the activity of the incorporated compounds/active ingredient. Further, level or degree of predictability of physical properties of multicomponent systems/compositions comprising (co)polymers is also low, given that said properties depend on thermodynamic and kinetic flexibility of (co)polymers included.
(6) Amount of guidance/direction provided by the inventor is low, because the specification does not teach any correlation between structural specificity of (co)polymers/compounds, functional agents/surfactants/excipients, other additives and required/claimed properties of the claimed product (i.e., ASD, pharmaceutical compositions comprising ASD for specific treatment), and only general statements what can be used/mixed are provided. The specification simply directs those skilled in the art to go figure out for themselves combinations of compounds that can be used in combination with said active agent of interest for preparing claimed products. For instance, claims disclose ASD comprising 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier that can be a (co)polymer (e.g., povidone, copovidone, hydroxypropyl methylcellulose acetate succinate, methacrylic acid/ethyl acrylate copolymers, and mixtures thereof) or mixtures of said (co)polymers with polysorbate (identified in the instant specification as a surfactant) or acid/citric acid. No information is provided in the instant specification what chemical structure of said (co)polymeric constituents, i.e., degree of polymerization, molecular weight distribution, composition and/or distribution of comonomers, etc.) should be used for providing the ASD suitable to be used for specific treatments. This implies that one should run tests on a wide spectrum of compounds for providing working examples, or potential candidates. Further, it is noted that the applicant was required to provide in the specification additional guidance and direction with respect to how to make ASD and/or compositions/formulations comprising said ASD to be used for a specific treatment (i.e., inflammatory diseases) in order for the application to be fully enabled. 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 and use the invention commensurate in scope with these claims without an undue amount of experimentation to identify the effective ASD and/or compositions comprising said ASD and amounts of components that would allow to eliminate or minimize site effects and/or provide an effective treatment.
(7) The specification provides examples of preparation of ASD by mixing said active ingredient with vinylpyrrolidone-vinyl acetate copolymer (here as Kollidone VA 64), or polyvinylpyrrolidone (here as Kollidone 30; Example 1), that further are included into the composition including mannitol, pregelatinized starch, talc, zinc stearate (Example 5), or sorbitol, lactose monohydrate, sodium starch glycolate, silicone dioxide, zinc stearate (Example 7). Applicant also provides the example of preparation of ASD by mixing said active ingredient with poly(methacrylic acid-co-ethyl acrylate), hydroxypropyl methylcellulose acetate succinate, polysorbate 80, citric acid (see Table 13). No information is provided regarding the structure of the (co)polymers to be used for preparation of ASD, i.e., degree of polymerization, molecular weight distribution, composition of comonomers, distribution of co-monomeric units (e.g., random copolymers, linear, branched, block-copolymers), etc. (Examples 1, 6).
(8) Quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure is great. In the present case, one of ordinary skill in the art would have to conduct time-consuming and costly experimental methods comprising functional and non-functional assays to (i) determine/identify what compound(s)/(copolymers/mixtures can be used as pharmaceutically acceptable carriers in preparation ASD as instantly claimed; (ii) what compounds can be used in pharmaceutical compositions comprising said ASD in combination with pharmaceutically acceptable excipients for the treatment of inflammatory diseases. No example is provided in the specification how to use said formulations (e.g., treatment schedule, effective concentrations of used active agents, additives/carriers/excipients). This implies that one of ordinary skill in the art would be required to conduct an undue amount of experimentation to prepare claimed ASD and composition/formulations comprising said ASD and to see what works for treatment of a specific condition with minimized side effects. Essentially, one of ordinary skill in the art has to figure out how to do this by themselves.
When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. In conclusion, Genetech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.” (Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997).
In response to applicant’s argument that the instant specification provides examples and considerable/sufficient direction and guidance how to make and used this invention, as stated previously, the examples in the specification demonstrate the use of particular products (e.g., Kollidon VA64, EUDRAGIT L 100-55, HPMCAS-MF) without clarifying the chemical structure of compounds/(co)polymers in use. The instant specification does not teach how a (co)polymer structure (i.e., degree of polymerization, molecular weight distribution, composition and distribution of co-monomers, etc.) should be controlled for providing desired results, i.e., amorphous solid dispersions. Further, it is noted that it is well known in the field that polymeric stabilization of ASD depends on polymer molecular weight, the glass transition temperature of a polymer, hydroscopicity and pH solubility of a polymer (see Iyer et al., Amorphous Solid Dispersions (ASDs): The Influence of Material Properties, Manufacturing Processes and Analytical Technologies in Drug Product Development; Pharmaceutics 2021, 13, 1682 and references cited therein). Therefore, the examiner maintains the position that quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure is great, and one of ordinary skill in the art would be required to conduct an undue amount of experimentation to prepare claimed amorphous solid dispersions and composition/formulations comprising said amorphous solid dispersions to be used for treatment of a specific condition.
Claim Rejections - 35 USC § 112(b)
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, 4-7, 9-12, 14-18, 24-28 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 pre-AIA the applicant regards as the invention.
Claim 1 discloses “An amorphous solid dispersion comprising 8-chloro-N-(4- (trifluoromethoxy)phenyl)quinolin-2-amine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier … selected from” that is not reasonably clear. Does this limitation imply that claimed amorphous solid dispersions may include all recited carriers? Applicant is advised to use a proper Markush group language, i.e., “is selected from the group consisting of A, B, … and C”. MPEP 2117. Similar is applied to claims 9, 12, 26; to claim 5 regarding the “ratio to at least one pharmaceutically acceptable carrier”; and to claims 6-7, 26 regarding the “combined weight of claimed active agent and the at least one pharmaceutically acceptable carrier” Clarification is required.
Claim 27 recites the limitation “a total amount of the at least one pharmaceutically acceptable carrier is in a range of 65% by weight” that is unclear, because the recited concentration range is not clearly defined. Clarification is required.
Claim 28 recites the limitation “carrier is a mixture of a 1st compound and a 2nd compounds” that is not reasonably clear, because a 1st compound and a 2nd compounds are not clearly defined. Clarification is required.
Claims 4, 10-11, 14-18, 24-25 are rejected as being dependent on rejected independent claim 1 and failing to cure the defect.
Response to Arguments
Applicant's arguments, filed 01/16/2026, have been fully considered, but they were not found to be persuasive for the reasons set forth above. New objections, rejections and arguments have been added to the record to clarify the position of the examiner and/or to address newly introduced amendments. Applicant is advised to clarify the claim language, the structure of the constituents to be included into the claimed amorphous solid dispersions and clearly point out the patentable novelty, which the applicant thinks the claims present in view of the state of the art, to place the application in condition for allowance.
Conclusion
No claim is allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA V. TCHERKASSKAYA whose telephone number is (571)270-3672. The examiner can normally be reached 9 am - 6 pm, Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615