Detailed Action
The present office action is in response to the remarks filed on 07 Aug 2025.
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
Claims 1, 3-16, 18-28, and 31-55 of the pending application have been examined on the merits. Acknowledgement is made of the amendments filed 07 Aug 2025. Acknowledgement is made of the cancelation of claims 2, 17, and 29-30.
Priority
Applicants identify the instant application, Serial #: 17/627,600, filed 14 Jan 2022, as a National Stage Entry of International Patent Application #: PCT/US2020/042389, filed 16 Jul 2020, which claims priority from U.S. Provisional Application #: 62/875,358, filed 17 Jul 2019.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 19 Feb 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Applicant Arguments
Regarding the rejections of claims 1, 3-16, 18-28, and 31-55 under obviousness-type double patenting over U.S. Patent No. 10,836,755, hereinafter ‘755, further in view of US 2013/0186801, hereinafter ‘801, US 2013/0273096, hereinafter ‘096, US 2017/0087180, hereinafter ‘180, Pifferi et al. (Il Famaco, 2003, 58:541-550; provided in the office action mailed 07 May 2025), hereinafter Pifferi, and King et al. (Remington’s Pharmaceutical Sciences, Ch. 90, 1985, 17th ed.; provided in the office action mailed 07 May 2025), hereinafter King, applicant arguments about lack of citation for ‘096 and incorrect cited reference claims for ‘755 have been considered and are persuasive. New grounds of rejection under obviousness-type double patenting against claims 1, 3-16, 18-28, and 31-55 can be found below. Applicant arguments on pgs. 23-26 regarding the following references have been fully considered and are not persuasive: ‘801, ‘180, Pifferi, and King.
Applicant argues that the office fails to establish that one would have been motivated to modify the composition of ‘755 in view of the secondary references. Applicant argues ‘801 is directed to formulations that do not include the instant compound and that are directed to treating CFTR which is unrelated to the diseases which the instantly claimed compound treats.
This is not persuasive. ‘801 is relied on to teach the ingredients of a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or glider and for providing motivation for including each additive in an oral formulation (see below) and is not relied on for teaching aficamten. The combination of references as a whole teach the invention. See MPEP § 2145(IV).
Applicant argues that ‘180 is directed to the use of sulfur compositions in treating nitric oxide deficiency disorders and related conditions. Applicant further argues there is no sulfur atom in the structure of aficamten and ‘180 and aficamten are structurally different in this way.
This is not persuasive. ‘180 is relied on for teaching the skill level of one having ordinary skill in the art. ‘180 teaches that modifying compositions of pharmaceutically acceptable dosages and forms would be known and that the artisan would have a reasonable expectation of success in modifying the formulations taught by ‘755, ‘801, ‘096, King, and Pifferi. See MPEP § 2145(IV).
Applicant argues that Pifferi and King are merely general references and that appropriate oral formulations will vary depending on the structure and activity of the active ingredient.
Pifferi is relied on for teaching that the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition. King is relied on for teaching various methods and motivations for different types of drug granulation. The rejection is based on a combination of references which include King and Pifferi and arguments against the references individually is not persuasive. See MPEP § 2145(IV).
Applicant further argues the potential options that could result from the combination of references would be functionally limitless with both the identity and amounts of ingredients varying in the extreme. Applicant argues there is no explanation how the specific formulations, tablets, and methods of the instant claims would be arrived at and instead there is merely an allegation that a skilled artisan would be motivated to make innumerable changes to the reference claims.
This is not persuasive. As taught by ‘755, ‘801, 096, ‘180, Pifferi, and King, the person of ordinary skill in the art has a reasonable expectation of success along with proper motivation to combine the references and arrive at the instantly claimed invention. Applicant has not presented evidence to show that there was no reasonable expectation of success. See MPEP § 2143.02(II) and MPEP § 2145(I). The rejection is amended in part and restated in part below.
Regarding the rejection of claims 1, 3-16, 18-28, and 31-55 under obviousness-type double patenting over copending Application No. 17/627,599, hereinafter ‘599, further in view of ‘801, ‘096, ‘180, Pifferi, and King, applicant arguments have been fully considered and are not persuasive. Applicant presents the same arguments regarding the combination of references of the obviousness-type double patenting rejection over ‘755, ‘801, ‘096, ‘180, Pifferi, and King. See the response to the arguments above. The rejection is maintained and restated below.
Regarding the rejection of claims 1, 3-16, 18-28, and 31-55 under obviousness-type double patenting over copending Application No. 17/627,590 further in view of ‘801, ‘096, ‘180, Pifferi, and King, applicant arguments have been fully considered and are persuasive. The copending application does not contain claims directed towards the instant compound of aficamten. The rejection is withdrawn.
Regarding the rejections of claims 1, 3-16, 18-28, and 31-55 under obviousness-type double patenting over copending Application Nos. 18/916,215, hereinafter ‘215, 18/355,195, hereinafter ‘195, and 18/365,038, hereinafter ‘038, further in view of ‘801, ‘096, ‘180, Pifferi, and King, applicant arguments have been fully considered but are not persuasive.
Applicant argues that because copending applications ‘215, ‘195, and ‘038 have later effective filing dates than the present application and because the present application is in condition for allowance the double patenting rejections should be withdrawn.
Because the rejections over ‘215, ‘195, and ‘038 are not the only rejections remaining in the application, the rejections are maintained. See MPEP § 804(I)(B)(1)(b)(i).
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 1, 3-16, 18-28, and 31-55 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 30-31, 38, and 46 of U.S. Patent No. in view of 10,836,755, hereinafter ‘755, and further in view of US 2013/0186801, hereinafter ‘801, US 2013/0273096, hereinafter ‘096, US 2017/0087180, hereinafter ‘180, Pifferi et al. (Il Famaco, 2003, 58:541-550), hereinafter Pifferi, and King et al. (Remington’s Pharmaceutical Sciences, Ch. 90, 1985, 17th ed.), hereinafter King.
'755 teaches a pharmaceutical composition of the following compound (ref claim 38):
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and a pharmaceutically acceptable excipient (ref claim 30). ‘755 further teaches treatment of hypertrophic cardiomyopathy or heart failure with preserved ejection fraction with the reference compound (ref claims 31 and 46). The specification of '755, cited for evidence, defines pharmaceutically acceptable compositions to include tablet, capsule, powder, liquid, suspension, suppository, and aerosol dosage forms (column 278, lines 59-62). However, '755 does not claim the compositions of the instant claims.
'801 teaches a pharmaceutical composition comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or a glider (paragraphs [0014]-[0021], paragraphs [0123]-[0130], paragraph [0134], paragraph [0137] and claim 1)
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'801 also teaches that fillers are useful for adding bulkiness to a pharmaceutical composition (paragraph [0107]), disintegrants hydrate a pharmaceutical composition and aid in tablet dispersion (paragraph [0106]), surfactants impart pharmaceutical compositions with enhanced solubility and/or wettability (paragraph [0107]), binders impart a pharmaceutical composition with enhanced cohesion or tensile strength (paragraph [0108]), lubricants are added to pharmaceutical compositions that are pressed into tablets and aid in compaction of granules into tablets (paragraph [0111]), and tablets are a pharmaceutical composition suitable for oral administration (paragraph [0229]). '801 teaches the formation of tablets by combining the active agent with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof, using a dry granulation process (paragraph [0277]). '801 further teaches a wet granulation process with a milling step to form a tablet of a composition of the active ingredient with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof (paragraph [0283]). '801 teaches blending intragranular ingredients with extragranular ingredients during the wet granulation process (paragraph [0283] and the graph on pg. 21). '801 also teaches various acceptable disintegrants, surfactants, binders, lubricants, and fillers (paragraph [0138]-[0148]).
'096 teaches the amount of any individual excipient in a pharmaceutical composition will vary depending on the nature and function of the excipient and particular needs of the composition and the optimal amount of any individual excipient is determined through routine experimentation (paragraph [0173]). '096 also teaches that generally, excipients will be present in the pharmaceutical composition in an amount of about 1% to 99% by weight (paragraph [0173]).
'180 teaches that conventional methods of formulating pharmaceutically acceptable dosage forms are known in the art. This includes varying dosage levels of the active ingredients to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient (paragraph [0105]). '180 teaches a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required (paragraph [0105]).
Pifferi teaches that interactions between excipients and active ingredients can be of two types, physical and chemical (pg. 543, column 2). Pifferi teaches that physical interactions can modify speed of dissolution or uniformity of dosage of a solid formulation (pg. 543, column 2). Pifferi also teaches that the ideal excipient should be able to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient (pg. 548, column 2).
King teaches that tablets remain popular as a dosage form because of the advantages afforded to the manufacturer (stability, convenience in packaging, shipping, etc.) and the patient (compactness, portability, accuracy of dosage, etc.) (pg. 1603, column 1). King also teaches that wet-granulation methods are popular due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets (pg. 1610, column 2). King further teaches that dry granulation eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying (pg. 1613, column 1).
It would be obvious to a person having ordinary skill in the art to combine reference claims 31 and 46 directed to treating hypertrophic cardiomyopathy or heart failure with preserved ejection fraction by administering aficamten and a pharmaceutical composition taught by ‘801 comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder in tablet form. The artisan would be motivated to create a pharmaceutical composition of aficamten in tablet form to afford advantages to the manufacturer and the patient.
The artisan would further be motivated to add: A filler to add bulkiness to the pharmaceutical composition, a binder to impart the pharmaceutical composition with enhanced cohesion, a disintegrant to hydrate the pharmaceutical composition and aid in tablet dispersion, a surfactant to enhance solubility of the pharmaceutical composition, and a lubricant to aid in the compaction of the pharmaceutical compositions granules into tablets.
It would be prima facie obvious to a person having ordinary skill in the art to combine the teaching of ‘755 and ‘801 to create a pharmaceutical composition of aficamten in tablet form with a filler, a binder, a disintegrant, a surfactant, and a lubricant as excipients and vary the concentration of active ingredient and concentration and identity of excipients with the expected result of an optimized formulation as taught by ‘096, ‘180, and Pifferi. ‘096 and ‘180 teach the artisan would be skilled enough to perform this optimization. ‘180 further teaches the artisan would be motivated to vary the concentration of the active ingredient to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient. Pifferi further teaches the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient.
It would be obvious to a person having ordinary skill in the art to combine the teachings of ’755 of a pharmaceutical composition of aficamten in tablet form with the teachings of King that the formation of tablets can occur with a wet- or dry-granulation method. The artisan would be motivated to use wet-granulation because of the greater probability that the granulation will meet all the physical requirements for the compression of good tablets. The artisan would be motivated to use dry-granulation because it eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying.
Claims 1, 3-16, 18-28, and 31-55 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting being unpatentable over claims 50-53 of copending Application No. 17/627,599, hereinafter ‘599, and further in view of ‘801, ‘096, ‘180, Pifferi, and King.
'599 claims a method for treating obstructive or nonobstructive hypertrophic cardiomyopathy (reference claim 52) or heart failure with preserved ejection fraction (reference claim 53) by administering a polymorph of aficamten (reference claim 50). By claiming a method of administering aficamten, ‘599 necessarily puts the inventors in possession of the compound. However, '599 does not teach a composition comprising the compound of the instant claims, a filler, a binder, a disintegrant, a surfactant, and a lubricant.
'801 teaches a pharmaceutical composition comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or a glider (paragraphs [0014]-[0021], paragraphs [0123]-[0130], paragraph [0134], paragraph [0137] and claim 1)
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'801 also teaches that fillers are useful for adding bulkiness to a pharmaceutical composition (paragraph [0107]), disintegrants hydrate a pharmaceutical composition and aid in tablet dispersion (paragraph [0106]), surfactants impart pharmaceutical compositions with enhanced solubility and/or wettability (paragraph [0107]), binders impart a pharmaceutical composition with enhanced cohesion or tensile strength (paragraph [0108]), lubricants are added to pharmaceutical compositions that are pressed into tablets and aid in compaction of granules into tablets (paragraph [0111]), and tablets are a pharmaceutical composition suitable for oral administration (paragraph [0229]). '801 teaches the formation of tablets by combining the active agent with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof, using a dry granulation process (paragraph [0277]). '801 further teaches a wet granulation process with a milling step to form a tablet of a composition of the active ingredient with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof (paragraph [0283]). '801 teaches blending intragranular ingredients with extragranular ingredients during the wet granulation process (paragraph [0283] and the graph on pg. 21). '801 also teaches various acceptable disintegrants, surfactants, binders, lubricants, and fillers (paragraph [0138]-[0148]).
'096 teaches the amount of any individual excipient in a pharmaceutical composition will vary depending on the nature and function of the excipient and particular needs of the composition and the optimal amount of any individual excipient is determined through routine experimentation (paragraph [0173]). '096 also teaches that generally, excipients will be present in the pharmaceutical composition in an amount of about 1% to 99% by weight (paragraph [0173]).
'180 teaches that conventional methods of formulating pharmaceutically acceptable dosage forms are known in the art. This includes varying dosage levels of the active ingredients to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient (paragraph [0105]). '180 teaches a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required (paragraph [0105]).
Pifferi teaches that interactions between excipients and active ingredients can be of two types, physical and chemical (pg. 543, column 2). Pifferi teaches that physical interactions can modify speed of dissolution or uniformity of dosage of a solid formulation (pg. 543, column 2). Pifferi also teaches that the ideal excipient should be able to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient (pg. 548, column 2).
King teaches that tablets remain popular as a dosage form because of the advantages afforded to the manufacturer (stability, convenience in packaging, shipping, etc.) and the patient (compactness, portability, accuracy of dosage, etc.) (pg. 1603, column 1). King also teaches that wet-granulation methods are popular due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets (pg. 1610, column 2). King further teaches that dry granulation eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying (pg. 1613, column 1).
It would be obvious to a person having ordinary skill in the art to combine the teachings of ‘599 directed to treating obstructive or nonobstructive hypertrophic cardiomyopathy or heart failure with preserved ejection fraction by administering aficamten and a pharmaceutical composition taught by ‘801 comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder in tablet form. The artisan would be motivated to create a pharmaceutical composition of aficamten in tablet form to afford advantages to the manufacturer and the patient.
The artisan would further be motivated to add: A filler to add bulkiness to the pharmaceutical composition, a binder to impart the pharmaceutical composition with enhanced cohesion, a disintegrant to hydrate the pharmaceutical composition and aid in tablet dispersion, a surfactant to enhance solubility of the pharmaceutical composition, and a lubricant to aid in the compaction of the pharmaceutical compositions granules into tablets.
It would be prima facie obvious to a person having ordinary skill in the art to combine the teaching of ‘599 and ‘801 to create a pharmaceutical composition of aficamten in tablet form with a filler, a binder, a disintegrant, a surfactant, and a lubricant as excipients and vary the concentration of active ingredient and concentration and identity of excipients with the expected result of an optimized formulation as taught by ‘096, ‘180, and Pifferi. ‘096 and ‘180 teach the artisan would be skilled enough to perform this optimization. ‘180 further teaches the artisan would be motivated to vary the concentration of the active ingredient to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient. Pifferi further teaches the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient.
It would be obvious to a person having ordinary skill in the art to combine the teachings of ’599 of a pharmaceutical composition of aficamten in tablet form with the teachings of King that the formation of tablets can occur with a wet- or dry-granulation method. The artisan would be motivated to use wet-granulation because of the greater probability that the granulation will meet all the physical requirements for the compression of good tablets. The artisan would be motivated to use dry-granulation because it eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-16, 18-28, and 31-55 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-6, 70-71, 91-99, 106, 108, and 126 of copending Application No. 18/365,038, hereinafter ‘038, and further in view of ‘801, ‘096, ‘180, Pifferi, and King.
'038 claims a method for treating obstructive hypertrophic cardiomyopathy by administering aficamten or a polymorph of aficamten (reference claim 1-6, 70-71, 91-99, 106, 108, and 126). By claiming a method of administering aficamten, ‘038 necessarily puts the inventors in possession of the compound. However, '038 does not teach a composition comprising aficamten, a filler, a binder, a disintegrant, a surfactant, and a lubricant.
'801 teaches a pharmaceutical composition comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or a glider (paragraphs [0014]-[0021], paragraphs [0123]-[0130], paragraph [0134], paragraph [0137] and claim 1)
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'801 also teaches that fillers are useful for adding bulkiness to a pharmaceutical composition (paragraph [0107]), disintegrants hydrate a pharmaceutical composition and aid in tablet dispersion (paragraph [0106]), surfactants impart pharmaceutical compositions with enhanced solubility and/or wettability (paragraph [0107]), binders impart a pharmaceutical composition with enhanced cohesion or tensile strength (paragraph [0108]), lubricants are added to pharmaceutical compositions that are pressed into tablets and aid in compaction of granules into tablets (paragraph [0111]), and tablets are a pharmaceutical composition suitable for oral administration (paragraph [0229]). '801 teaches the formation of tablets by combining the active agent with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof, using a dry granulation process (paragraph [0277]). '801 further teaches a wet granulation process with a milling step to form a tablet of a composition of the active ingredient with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof (paragraph [0283]). '801 teaches blending intragranular ingredients with extragranular ingredients during the wet granulation process (paragraph [0283] and the graph on pg. 21). '801 also teaches various acceptable disintegrants, surfactants, binders, lubricants, and fillers (paragraph [0138]-[0148]).
'096 teaches the amount of any individual excipient in a pharmaceutical composition will vary depending on the nature and function of the excipient and particular needs of the composition and the optimal amount of any individual excipient is determined through routine experimentation (paragraph [0173]). '096 also teaches that generally, excipients will be present in the pharmaceutical composition in an amount of about 1% to 99% by weight (paragraph [0173]).
'180 teaches that conventional methods of formulating pharmaceutically acceptable dosage forms are known in the art. This includes varying dosage levels of the active ingredients to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient (paragraph [0105]). '180 teaches a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required (paragraph [0105]).
Pifferi teaches that interactions between excipients and active ingredients can be of two types, physical and chemical (pg. 543, column 2). Pifferi teaches that physical interactions can modify speed of dissolution or uniformity of dosage of a solid formulation (pg. 543, column 2). Pifferi also teaches that the ideal excipient should be able to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient (pg. 548, column 2).
King teaches that tablets remain popular as a dosage form because of the advantages afforded to the manufacturer (stability, convenience in packaging, shipping, etc.) and the patient (compactness, portability, accuracy of dosage, etc.) (pg. 1603, column 1). King also teaches that wet-granulation methods are popular due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets (pg. 1610, column 2). King further teaches that dry granulation eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying (pg. 1613, column 1).
It would be obvious to a person having ordinary skill in the art to combine the teachings of ‘038 directed to treating obstructive hypertrophic cardiomyopathy by administering aficamten and a pharmaceutical composition taught by ‘801 comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder in tablet form. The artisan would be motivated to create a pharmaceutical composition of aficamten in tablet form to afford advantages to the manufacturer and the patient.
The artisan would further be motivated to add: A filler to add bulkiness to the pharmaceutical composition, a binder to impart the pharmaceutical composition with enhanced cohesion, a disintegrant to hydrate the pharmaceutical composition and aid in tablet dispersion, a surfactant to enhance solubility of the pharmaceutical composition, and a lubricant to aid in the compaction of the pharmaceutical compositions granules into tablets.
It would be prima facie obvious to a person having ordinary skill in the art to combine the teaching of ‘038 and ‘801 to create a pharmaceutical composition of aficamten in tablet form with a filler, a binder, a disintegrant, a surfactant, and a lubricant as excipients and vary the concentration of active ingredient and concentration and identity of excipients with the expected result of an optimized formulation as taught by ‘096, ‘180, and Pifferi. ‘096 and ‘180 teach the artisan would be skilled enough to perform this optimization. ‘180 further teaches the artisan would be motivated to vary the concentration of the active ingredient to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient. Pifferi further teaches the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient.
It would be obvious to a person having ordinary skill in the art to combine the teachings of ’038 of a pharmaceutical composition of aficamten in tablet form with the teachings of King that the formation of tablets can occur with a wet- or dry-granulation method. The artisan would be motivated to use wet-granulation because of the greater probability that the granulation will meet all the physical requirements for the compression of good tablets. The artisan would be motivated to use dry-granulation because it eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-16, 18-28, and 31-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 12-13, 51-52, 65-66, 91-96, 112-114, 120-121, and 162 of copending Application No. 18/355,195, hereinafter ‘195, and further in view of ‘801, ‘096, ‘180, Pifferi, and King.
'195 claims a method for treating obstructive hypertrophic cardiomyopathy by administering aficamten or a polymorph of aficamten (reference claims 1-2, 12-13, 51-52, 65-66, 91-96, 112-114, 120-121, 162). By claiming a method of administering aficamten, ‘195 necessarily puts the inventors in possession of the compound. However, '195 does not teach a composition comprising aficamten, a filler, a binder, a disintegrant, a surfactant, and a lubricant.
'801 teaches a pharmaceutical composition comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or a glider (paragraphs [0014]-[0021], paragraphs [0123]-[0130], paragraph [0134], paragraph [0137] and claim 1)
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'801 also teaches that fillers are useful for adding bulkiness to a pharmaceutical composition (paragraph [0107]), disintegrants hydrate a pharmaceutical composition and aid in tablet dispersion (paragraph [0106]), surfactants impart pharmaceutical compositions with enhanced solubility and/or wettability (paragraph [0107]), binders impart a pharmaceutical composition with enhanced cohesion or tensile strength (paragraph [0108]), lubricants are added to pharmaceutical compositions that are pressed into tablets and aid in compaction of granules into tablets (paragraph [0111]), and tablets are a pharmaceutical composition suitable for oral administration (paragraph [0229]). '801 teaches the formation of tablets by combining the active agent with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof, using a dry granulation process (paragraph [0277]). '801 further teaches a wet granulation process with a milling step to form a tablet of a composition of the active ingredient with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof (paragraph [0283]). '801 teaches blending intragranular ingredients with extragranular ingredients during the wet granulation process (paragraph [0283] and the graph on pg. 21). '801 also teaches various acceptable disintegrants, surfactants, binders, lubricants, and fillers (paragraph [0138]-[0148]).
'096 teaches the amount of any individual excipient in a pharmaceutical composition will vary depending on the nature and function of the excipient and particular needs of the composition and the optimal amount of any individual excipient is determined through routine experimentation (paragraph [0173]). '096 also teaches that generally, excipients will be present in the pharmaceutical composition in an amount of about 1% to 99% by weight (paragraph [0173]).
'180 teaches that conventional methods of formulating pharmaceutically acceptable dosage forms are known in the art. This includes varying dosage levels of the active ingredients to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient (paragraph [0105]). '180 teaches a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required (paragraph [0105]).
Pifferi teaches that interactions between excipients and active ingredients can be of two types, physical and chemical (pg. 543, column 2). Pifferi teaches that physical interactions can modify speed of dissolution or uniformity of dosage of a solid formulation (pg. 543, column 2). Pifferi also teaches that the ideal excipient should be able to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient (pg. 548, column 2).
King teaches that tablets remain popular as a dosage form because of the advantages afforded to the manufacturer (stability, convenience in packaging, shipping, etc.) and the patient (compactness, portability, accuracy of dosage, etc.) (pg. 1603, column 1). King also teaches that wet-granulation methods are popular due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets (pg. 1610, column 2). King further teaches that dry granulation eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying (pg. 1613, column 1).
It would be obvious to a person having ordinary skill in the art to combine the teachings of ‘195 directed to treating obstructive hypertrophic cardiomyopathy by administering aficamten or a polymorph of aficamten and a pharmaceutical composition taught by ‘801 comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder in tablet form. The artisan would be motivated to create a pharmaceutical composition of aficamten in tablet form to afford advantages to the manufacturer and the patient.
The artisan would further be motivated to add: A filler to add bulkiness to the pharmaceutical composition, a binder to impart the pharmaceutical composition with enhanced cohesion, a disintegrant to hydrate the pharmaceutical composition and aid in tablet dispersion, a surfactant to enhance solubility of the pharmaceutical composition, and a lubricant to aid in the compaction of the pharmaceutical compositions granules into tablets.
It would be prima facie obvious to a person having ordinary skill in the art to combine the teaching of ‘195 and ‘801 to create a pharmaceutical composition of aficamten in tablet form with a filler, a binder, a disintegrant, a surfactant, and a lubricant as excipients and vary the concentration of active ingredient and concentration and identity of excipients with the expected result of an optimized formulation as taught by ‘096, ‘180, and Pifferi. ‘096 and ‘180 teach the artisan would be skilled enough to perform this optimization. ‘180 further teaches the artisan would be motivated to vary the concentration of the active ingredient to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient. Pifferi further teaches the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient.
It would be obvious to a person having ordinary skill in the art to combine the teachings of ’195 of a pharmaceutical composition of aficamten in tablet form with the teachings of King that the formation of tablets can occur with a wet- or dry-granulation method. The artisan would be motivated to use wet-granulation because of the greater probability that the granulation will meet all the physical requirements for the compression of good tablets. The artisan would be motivated to use dry-granulation because it eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-16, 18-28, and 31-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of copending Application No. 18/916,215, hereinafter ‘215, and further in view of ‘801, ‘096, ‘180, Pifferi, and King.
'215 claims a method for treating obstructive hypertrophic cardiomyopathy by administering aficamten (reference claims 1-13 and 16-87). By claiming a method of administering aficamten, ‘215 necessarily puts the inventors in possession of the compound. However, '215 does not teach a composition comprising aficamten, a filler, a binder, a disintegrant, a surfactant, and a lubricant.
'801 teaches a pharmaceutical composition comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder or a glider (paragraphs [0014]-[0021], paragraphs [0123]-[0130], paragraph [0134], paragraph [0137] and claim 1)
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'801 also teaches that fillers are useful for adding bulkiness to a pharmaceutical composition (paragraph [0107]), disintegrants hydrate a pharmaceutical composition and aid in tablet dispersion (paragraph [0106]), surfactants impart pharmaceutical compositions with enhanced solubility and/or wettability (paragraph [0107]), binders impart a pharmaceutical composition with enhanced cohesion or tensile strength (paragraph [0108]), lubricants are added to pharmaceutical compositions that are pressed into tablets and aid in compaction of granules into tablets (paragraph [0111]), and tablets are a pharmaceutical composition suitable for oral administration (paragraph [0229]). '801 teaches the formation of tablets by combining the active agent with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof, using a dry granulation process (paragraph [0277]). '801 further teaches a wet granulation process with a milling step to form a tablet of a composition of the active ingredient with a filler, diluent, disintegrant, surfactant, glidant, binder, lubricant, or any combination thereof (paragraph [0283]). '801 teaches blending intragranular ingredients with extragranular ingredients during the wet granulation process (paragraph [0283] and the graph on pg. 21). '801 also teaches various acceptable disintegrants, surfactants, binders, lubricants, and fillers (paragraph [0138]-[0148]).
'096 teaches the amount of any individual excipient in a pharmaceutical composition will vary depending on the nature and function of the excipient and particular needs of the composition and the optimal amount of any individual excipient is determined through routine experimentation (paragraph [0173]). '096 also teaches that generally, excipients will be present in the pharmaceutical composition in an amount of about 1% to 99% by weight (paragraph [0173]).
'180 teaches that conventional methods of formulating pharmaceutically acceptable dosage forms are known in the art. This includes varying dosage levels of the active ingredients to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient (paragraph [0105]). '180 teaches a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required (paragraph [0105]).
Pifferi teaches that interactions between excipients and active ingredients can be of two types, physical and chemical (pg. 543, column 2). Pifferi teaches that physical interactions can modify speed of dissolution or uniformity of dosage of a solid formulation (pg. 543, column 2). Pifferi also teaches that the ideal excipient should be able to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient (pg. 548, column 2).
King teaches that tablets remain popular as a dosage form because of the advantages afforded to the manufacturer (stability, convenience in packaging, shipping, etc.) and the patient (compactness, portability, accuracy of dosage, etc.) (pg. 1603, column 1). King also teaches that wet-granulation methods are popular due to the greater probability that the granulation will meet all the physical requirements for the compression of good tablets (pg. 1610, column 2). King further teaches that dry granulation eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying (pg. 1613, column 1).
It would be obvious to a person having ordinary skill in the art to combine the teachings of ‘215 directed to treating obstructive hypertrophic cardiomyopathy by administering aficamten or a polymorph of aficamten and a pharmaceutical composition taught by ‘801 comprising Compound 1, a filler, a disintegrant, a surfactant, a diluent, a lubricant, and a binder in tablet form. The artisan would be motivated to create a pharmaceutical composition of aficamten in tablet form to afford advantages to the manufacturer and the patient.
The artisan would further be motivated to add: A filler to add bulkiness to the pharmaceutical composition, a binder to impart the pharmaceutical composition with enhanced cohesion, a disintegrant to hydrate the pharmaceutical composition and aid in tablet dispersion, a surfactant to enhance solubility of the pharmaceutical composition, and a lubricant to aid in the compaction of the pharmaceutical compositions granules into tablets.
It would be prima facie obvious to a person having ordinary skill in the art to combine the teaching of ‘215 and ‘801 to create a pharmaceutical composition of aficamten in tablet form with a filler, a binder, a disintegrant, a surfactant, and a lubricant as excipients and vary the concentration of active ingredient and concentration and identity of excipients with the expected result of an optimized formulation as taught by ‘096, ‘180, and Pifferi. ‘096 and ‘180 teach the artisan would be skilled enough to perform this optimization. ‘180 further teaches the artisan would be motivated to vary the concentration of the active ingredient to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration, without being toxic to the patient. Pifferi further teaches the artisan would be motivated to modify the concentration and identity of the excipients in a pharmaceutical composition to guarantee the dose, stability, and release of the active ingredient and that it should possess particular chemical, physical, and mechanical characteristics to optimize the formulation's performance during the manufacturing phase and when used by the patient.
It would be obvious to a person having ordinary skill in the art to combine the teachings of ’215 of a pharmaceutical composition of aficamten in tablet form with the teachings of King that the formation of tablets can occur with a wet- or dry-granulation method. The artisan would be motivated to use wet-granulation because of the greater probability that the granulation will meet all the physical requirements for the compression of good tablets. The artisan would be motivated to use dry-granulation because it eliminates a number of steps and that it is preferred when tablet ingredients are sensitive to moisture or are not able to withstand elevated temperatures during drying.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Correspondence
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625