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
This is in response to February 20, 2024 Preliminary Amendment in the above-identified application.
Claims 1-15, 20, 23-25 and 27 are pending, claim 12 is original, and claims 1-11, 13-15, 20 and 22-25 are amended, claim 27 is new and claims 16-19, 21-22 and 26 are cancelled in the above identified application.
Priority
The present U.S. Appln. Ser. No.: 18/533,710, Filed: December 8, 2023 is a 35 U.S.C. 111(a) By-Pass Appln., which is a continuation of WO 2022/258584 A1 (i.e., PCT/EP2022/065342, Intern.’ Filing Date: June 07, 2022), which claims foreign priority to EP 21178622.3, Filed: June 9, 2021.
Comments
Claim 1 of the February 20, 2024 Preliminary Amendment is identified as “currently amended”, but there appears to be no difference with that of claim 1, which part of the claim set of the originally filed December 8, 2023 disclosure.
Claim Rejections - 35 USC § 112
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 24 and 25, respectively, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd 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.
In general, the claims of the present invention fail to define the metes and bounds of the claimed invention due to use of indefinite, vague, ambiguous or unclear or poorly defined functional terms and/or language (i.e., such that exact scope of the claimed invention cannot be ascertained) without support from the specification within the claim itself. Claims must particularly point out and distinctly the claimed invention. Moreover, claims identified above also lack clarity, due to unnecessary use of repetitive and/or redundant terms.
The claim fails to provide a standard or "blaze marks" in the intrinsic evidence (specification, claims, prosecution history) that would enable a person of ordinary skill in the art to determine, with reasonable certainty, the exact boundaries of the claimed chemical structures; i.e., it’s unclear what the exact scope of the resulting chemical structure is meant to be.
[1] Claim 24-25 are rejected for lacking clarity and for being indefinite, vague, ambiguous, for being directed to a process that defines steps that recite indefinite broad terms, such as “suitable” preceding terms base, acid, solvent, substantial amounts and further without definitive reaction conditions (i.e., what are reaction times, temperatures employed in each step, specific reactant, reagent, solvent equivalents and the like employed in each step?) such that the metes and bound of the claimed invention are indeterminate (i.e., it is unclear what constitutes a suitable acid, base or solvent or what a substantial amount is?). Identified terms in steps that include those indefinite and broad terms are identified below:
[a] in claim 24:
suitable base in the presence of a suitable solvent (i.e., e.g., as in step (a));
“in presence of a suitable base in presence of a suitable solvent . . . (i.e., e.g., as in step (b))”;
“purifying by filtration a suspension of the crude product of the compound of formula (I) in a suitable solvent and a suitable acid to remove substantial amounts of dimer sulfate and to obtain a filtrate comprising substantial amounts of the compound of formula (I) (i.e., e.g., as in step (c))”;
[b] in claim 25:
(a) concentrating the filtrate of step (c) comprising substantial amounts of the compound of formula (I) under vacuum to provide a suspension;
(b) adding water and a suitable base to a suspension comprising the compound of formula (I) and after adjustment of the pH to 6.7±0.5 the reaction is stirred to afford a precipitate comprising the compound of formula (I);
(c) filtrating a precipitate comprising the compound of formula (I), followed by washing with a suitable solvent and drying in vacuo to afford crystallized (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide;
(d) adding a suitable solvent and water to (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide, followed by heating the suspension to between about 40° C. to about 80° C. and filtering and washing the resulting solution with a suitable solvent;
(e) concentrating a solution comprising to (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide in a suitable solvent in vacuo;
(f) solvent exchanging a solution comprising (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide by distillation and stirring the suspension to precipitate (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide; and
(g) filtering and drying a suspension of (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide in a suitable solvent in vacuo to afford crystalline polymorphic Form A.
Applicants are requested to amend the above identified claims to include specific reactions conditions, reagents, reactants, solvents, associated molar equivalents of reactants, reagents etc. at paras. [0070]-[0083] and [00129]-[00137] (i.e. Examples 1-9) pages 11-13 and 22-23, respectively.
Claim Rejections - 35 USC § 112
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 2-10 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 1 upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In particular, independent claim 1:
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; and
corresponding dependent claims 2 to 10, respectively, all are directed to a crystalline polymorphic Form A recites:
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Claim 1 establishes the core invention as a polymorph Form A (i.e., specifically defining and covering the entire Form A physical entity with a set of characteristic XRPD peaks distinguishable from other polymorphs based in its X-ray fingerprint), while dependent claims 2-7 provide additional structural peaks, which uniquely identify Form A. Claims1 to 7 directed to a single polymorphic Form A with characterizing XRPD peaks that define it. The same rationale applies to pending claims 8-10, which are directed to additional characterization data associated with melting point and differential scanning calorimetry, IR Spectrum and Raman Spectrum, which all of the characterizing data is directed to and defines a single solid form.
Dependent claims 2 to 7 recite that each polymorph is further characterized by two (2) X-ray powder diffraction peaks already defined in claim 1 and as identified in the Xray diffraction pattern of Figure 1 in claim 7. Because claim 1 already requires the presence of all seven aforementioned peaks, a dependent claims 2 to 7 reciting the presence of only one or more of those same peaks does not add a further limitation or narrow the scope of the claim 1, because additional peaks associated with polymorph A are considered obvious as per well-known crystallization techniques in the art.
A dependent claim must restrict the scope of the claim from which it depends; here the dependent claims are commensurate in scope with or broader than the independent claim.
However, if Applicants amend claim 1 by deleting the term “form A”, the scope of claim 1 would be broadened, i.e., not solely limited to Form A but encompasses all forms), including dependent claims 2-7 in their current form would no longer be further limiting and acceptable as written now.
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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 11-15 and 24-25 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2021/116055 A1 to Hoffmann La Roche Inc. (i.e., Intern.’l Filing Date: 08 December 2020; Earliest Priority Data; 10 December 2019; i.e., “WO ‘055 Appln.”)
The WO ‘055 Appln. discloses and teaches methyl quinazolinone derivative compounds (i.e., which includes racemate and isomeric forms) of the formula (I):
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; or a pharmaceutically acceptable salt thereof.
In particular, while WO ‘055 Appln. discloses:
the (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide isomer, which is the specific identical compound isomer as taught in the claimed invention (i.e., see Example 1 of the WO ‘055 Appln. at page 25, lines 1-20):
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where the compound is isolated as a colorless (i.e., amorphous) solid (i.e., see page 25, line 17)
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corresponding pharmaceutical compositions thereof;
compounds are BRAF inhibitors taught therein used for the treatment of BRAF associated cancers;
methods or uses for the treatment of cancers, such as melanoma or non-small lung cancer
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synthetic methods for preparation of the compound of the (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide isomer,
Moreover, it is conventionally understood in the chemical arts that a solid that is not crystalline is defined as an amorphous solid (i.e., constituent particles, atoms, ions or molecules are randomly arranged, rather than in a regular repeating lattice without a well-defined internal structure and sharp melting points, amorphous solids lack long range order and soften gradually over a range of temperatures rather than melting sharply ) The instant specification provides associated information and data associated with amorphous (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide is hygroscopic and is characterized by enhanced biophysical properties such as for instance solubility or bioavailability. (i.e., e.g., see [0026]) ]; which is specifically supported by:
FIG. 6 is a sorption/desorption curve of amorphous (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide obtained by dynamic vapour sorption (DVS). Masschange ˜3.8% from 0%-90% RH; the amorphous form is hygroscopic. Recrystallization to Form A observed in high humidity storage experiments;
FIG. 10 is a IR spectrum of amorphous (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide; and
amorphous of claims 12 to 16 solid compound form of the instant invention is characterized by melting point, transition glass temperature, Raman IR as here is described
Therefore, the WO ‘055 Appln. anticipates the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 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.
Claims 1-10, 20 and 23 is rejected under 35 U.S.C. 103 as being unpatentable over:
WO 2021/116055 A1 to Hoffmann La Roche Inc. (i.e., Intern.’l Filing Date: 08 December 2020; Earliest Priority Data; 10 December 2019; i.e., “WO ‘055 Appln.”)
WO 2020/261156 A1 to Array Biopharma Inc. (i.e., Intern.’l Filing Date: 24 June 2020; Earliest Priority Data; 28 June 2019; i.e., “WO ‘156 Appln.”),
alone, in view of or in combination with:
Kumar et al. Pharmaceutical Technology (March 2, 2008) Vol. 32, Issue 3.
Raza et al., “ Polymorphism: The Phenomenon Affecting Performance of Drugs”, Review Article: Pharm Sci, 1(2), 10, Pub.: July 28, 2014, pp. 1-10; and
Lee. “A Practical Guide To Pharmaceutical Polymorph Screening & Selection”, Asian Journal Of Pharmaceutical Sciences, 9 (2014) 163-175
The WO ‘055 Appln. discloses and teaches methyl quinazolinone derivative compounds (i.e., which includes racemate and isomeric forms) of the formula (I):
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; or a pharmaceutically acceptable salt thereof.
In particular, while WO ‘055 Appln. discloses:
the (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide isomer, which is the specific identical compound isomer as taught in the claimed invention (i.e., see Example 1 of the WO ‘055 Appln. at page 25):
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corresponding pharmaceutical compositions thereof;
compounds are BRAF inhibitors taught therein used for the treatment of BRAF associated cancers;
methods or uses for the treatment of cancers, such as melanoma or non-small lung cancer
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synthetic methods for preparation of the compound identified supra.
While the WO ‘055 Appln. teaches a solid form of the compound (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide in Example 1 (i.e. a non-crystalline compound is considered an amorphous in the chemical arts, which lacks a regular ordered structure of particles , the WO ‘055 Appln. does not disclose, teach or state:
the specific crystalline polymorphic Form A of (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide . . ” of the claimed invention, or
corresponding characteristic crystalline data (i.e., such as characteristic XRPD peaks):
However, one of ordinary skill in the art would routinely understand that application of art known purification techniques are tailored to the chemical and physical nature of the compound being purified, which is essential for high purity for accurate analytical, pharmaceutical or industrial use. One such technique used in the purification of solid organic compounds is crystallization,
which relies on differences in solubility between a desired compound and its impurities in a specific solvent. It involves dissolving the impure compound in the minimum hot solvent, filtering that hot solution to remove insoluble impurities, allowing slow cooling to form crystals, filtering, and drying the purified crystals.
While the WO ‘055 Appln. teaches a solid form of the compound (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide in Example 1 (i.e. a non-crystalline compound is considered an amorphous in the chemical arts, which lacks a regular ordered structure of particles , the WO ‘055 Appln. does not disclose, teach or state:
the specific crystalline polymorphic Form A of (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide . . ” of the claimed invention, or
corresponding characteristic crystalline data (i.e., such as characteristic XRPD peaks):
However, one of ordinary skill in the art would routinely understand that application of art known purification techniques are tailored to the chemical and physical nature of the compound being purified, which is essential for high purity for accurate analytical, pharmaceutical or industrial use. One such technique used in the purification of solid organic compounds is crystallization, which relies on difference in solubility between a desired compound and its impurities in a specific solvent.It involves dissolving the impure compound in the minimum hot solvent, filtering the hot solution to remove insoluble impurities, allowing slow cooling to form crystals, filtering, and drying the purified crystals.
Such technical expertise in conventionally applied in routine salt and polymorphic screening, which incorporates extensive scientific literature and knowledge in the areas of drug development to find alternate polymorphic forms to potentially optimize a drug's properties, such as its solubility, stability, biological activity and bioavailability to potentially improve enhanced pharmacological properties, drug delivery, increased stability in certain environments, synthetic accessibility and/or manufacturing costs as taught by review articles that teach conventional techniques for the synthesis and formation of polymorphic forms as taught by review articles, such as, but not limited to Kumar et al., Raza et al. and Lee references directed to practical applications or guide to pharmaceutical polymorph screening & selection
Based on such teachings, an ordinary artisan would meet with an expectation of success and/or it would be obvious to try and apply routine conventional purification techniques using crystallization to generate the crystalline polymorph of the compound (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide of the present invention as per the chemical and physical properties taught by the disclosures of the instant invention and the WO ‘055 Appln.
One of ordinary skill in the art would have been motivated in applying the knowledge taught in the art to make and use corresponding novel and unobvious crystalline polymorphic forms of 4-[(7-chloro-2-methoxybenzo[b][1,5]n aphthyridin-10-yl)amino]-2,6-bis(pyrrolidin-1 -ylmethyl)phenol for reasons discussed supra, because the need remains in drug development to discover and improved new alternate salt or polymorphic forms for practical use in therapeutic treatment of b-Raf associated cancers.
Claims 24 and 25 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/116055 A1 to Hoffmann La Roche Inc. (i.e., Intern.’l Filing Date: 08 December 2020; Earliest Priority Data; 10 December 2019; i.e., “WO ‘055 Appln.”).
Claims 24-25 are directed to:
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; and
corresponding or associated process steps as discussed below.
The WO ‘055 Appln. discloses a method or process for making the methyl quinazolinone derivative compounds; i.e., inc. racemate and isomeric forms of formula (I) of the claimed invention:
Racemate
(3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide
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isomer reads on claimed invention
(i.e., see Example 1 - WO ‘055 Appln. at page 25).
While Scheme 1 of the WO ‘055 Appln. discloses and teaches preparation process for making N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxy-phenyl]-3-fluoro-pyrrolidine-1-sulfonamide compounds, it is directed to a longer synthetic route, which incorporates identical synthetic steps (a) to (c) that read on claims 24- 25 of the claimed invention (inc. with identical intermediates, where reactants, reagents and/or reaction conditions are adaptable within skill of the ordinary artisan), but the specific process steps of the WO ‘055 Appln. do not disclose, teach or identical, reaction steps and/or reaction conditions, which are distinguished from those of the claimed invention.
In particular, schematic shown below indicate all the key changes bet. claimed invention & WO‘055 Appln.:
Claims 24-25 of the Present Invention
WO’055 Appln.
Step B2- 3 Step Synthesis convergent synthesis strategy
(i.e., see claim 24)
Step B2- 2 steps separately make intermediate or smaller precursor
Fragments
Step A includes use of Amido sulfonamide
H₂NSO₂NH₂ to make pyrrolidine-1-sulfonamide
nucleophilic reagent
Step C Purification Steps – Standard Work-up (i.e., see claim 25)
5 Step Synthesis (full synthesis strategy)
Corresp. Step includes use of Chlorosulfonyl isocyanate
ClSO₂NCO to make pyrrolidine-1-sulfonamide
electrophilic reagent
Purification Steps – Standard Work-up
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Moreover, the WO ‘055 Appln. teaches that an ordinary artisan would adapt known knowledge and conventional techniques within the organic chemical arts to prepare compounds or pharmaceutically acceptable salts, polymorphic forms or solvates thereof, optimize reaction conditions and other factors to generate different crystalline compounds of similar chemical structures, apply convergent synthetic strategies to shorten reaction synthetic sequences, adapt purification techniques, etc. such as processes of the claimed invention. This is supported by the following excerpt from the WO ‘055 Appln. specification (i.e., see WO ‘055 Appln, at page 6, lines 4-15):
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Thus, a person of ordinary skill in the art would recognize the ability:
to adapt same techniques from the WO ‘055 Appln and those known in the conventional art to make crystalline polymorphic forms of the (3R)-N-[2-cyano-4-fluoro-3-(3-methyl-4-oxo-quinazolin-6-yl)oxynyl]-3-fluoro-pyrrolidine-1-sulfonamide of the claimed invention;
to make polymorphic form of the species of the instant invention, based upon the chemical and physical properties taught by the disclosures of the cited references (i.e., with WO ‘055 Appln teaching the compound species per se, and compound genus of the WO ‘156 being virtually identical defining same compound core with a small predictable number of functional groups (i.e., sans R2 ≠ H therein), potentially optimize properties, because the WO ‘156 Appln. teaches that it is possible to make stable polymorphic forms of corresponding derivatives with same chemical core structure (i.e., obvious to try substitution of R2 ≠ H) to result in the ability to fine tune known techniques to form polymorphic forms, even despite unpredictable changes in activity and polymorphism of the present invention.
Based on the foregoing and the teachings of the artisan ordinary artisan would meet with an expectation of success in make polymorphic forms via improved reaction conditions and more chemically efficient synthetic routes for compound per se of the present invention taught in the WO ‘055 Appln, because the ordinary artisan routinely employs technical expertise in routine polymorphic screening, incorporating extensive scientific literature and knowledge in the areas of drug development to find alternate polymorphic forms to improve drug delivery, increased stability in certain environments, or enhanced pharmacological properties, such as its solubility, stability, and bioavailability, synthetic accessibility and/or manufacturing costs (i.e., Kumar references).
One of ordinary skill in the art would have been motivated in applying the knowledge taught in the art to make, use corresponding novel and unobvious crystalline polymorphic forms of 4-[(7-chloro-2-methoxybenzo[b][1,5]n aphthyridin-10-yl)amino]-2,6-bis(pyrrolidin-1-ylmethyl)phenol and optimize synthetic reaction strategies and conditions in the preparation of corresponding crystalline polymorphs, solvates and the as discussed supra, because the need remains in drug development to discover and improved new alternate salt or polymorphic forms for practical use in therapeutic treatment of B-Raf associated cancers.
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689. The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Kortney L. Klinkel, can be reached on 571-270-5239.
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/G.C.H./
Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627