DETAILED ACTION
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 .
Formal Matters
Applicant’s response in the reply filed on 16 January 2026 are acknowledged and have been fully considered. Claims 1-10 are pending. Claims 1-5 are under consideration in the instant office action. Claims 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 15 June 2023 is noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-5) in the reply filed on 16 January 2026 is acknowledged. Additionally, Applicant’s election of sodium stearyl fumarate as the binder; sodium starch glycolate as the disintegrant; and colloidal silicon dioxide as the excipient type in the reply filed on 16 January 2026 is also acknowledged. The traversal is on the ground(s) that both 37 C.F.R. $1.141 and MPEP 806.04(a) provide that a reasonable number of species may be claimed in one application. It is respectfully submitted that the number of species claimed in the present application does not exceed such a reasonable number, particularly in view of the structural similarity of, and the similar field of search required for, the claimed species. Reconsideration and withdrawal of the restriction/election requirement, therefore, are requested.
This is not found persuasive because the standard for the restriction was done under the lack of unity provisions as the instant application is a 371 application. Groups I-II lack unity of invention because even though the inventions of these groups require the technical feature of the tablet formulation of claim 1, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Kim et al. (KR20190028903, IDS reference 6/15/23). Kim et al. disclose a rapid capsule composition containing a raw drug, an excipient, a binder and a granule prepared from a disintegrant. More particularly, the present invention relates to a triazolopyrimidine compound, a lactose monohydrate as an excipient, A low-substituted hydroxypropylcellulose LH21 (low-substituted hydroxypropylcellulose LH21) and a low-substituted hydroxypropylcellulose LH21 (low-substituted hydroxypropylcellulose LH21) as a disintegrant (abstract). The binder is added to increase the strength of the product by imparting elasticity and tackiness to the sample when the powder is formed in the fields of pharmaceuticals, catalysts and the like. In addition, the field of ceramics refers to a substance to be added to increase the strength of a product when the sample is sintered or formed, preferably to give a binding force to the drug to facilitate preparation of tablets and the like. In the present invention, ABN401, a solvothyrazine compound, and an excipient were tested for their stability. The disintegrant of the present invention is added for the purpose of promoting the disintegration of tablets, capsules, granules or the like in the digestive juices. Starch and carbonate, and was selected as an excipient having stability through the mutual stability test between ABN401, which is the most preferable triazolo pyrazine compound in the present invention, and an excipient. The excipient means that the drug is biocompatible in the body of the patient and helps to avoid side effects while forming the formulation together with the original drug. The excipient can be divided into various types depending on the role used in the preparation. Depending on the amount of the raw material, it may be added to the diluent or the weight of the filler to make the tablet an appropriate size, or a small-sized excipient, or a binding agent, a tablet or a granule, A disintegrant to promote disintegration of the formulation, a lubricant added to improve the fluidity of the granule and to prevent friction and sticking between particles, an adsorbent to assist in the absorption of the liquid raw material, And release control additives used in accordance with the hydrophilicity, hydrophobicity and pH dependency used. At this time, each excipient does not only serve as one of the excipients but also functions as a different function depending on the composition ratio contained in the formulation. The triazolo pyrazine compounds include, but are not limited to, triazolopyrazine derivatives and pharmaceutically acceptable salts thereof disclosed in Korean Patent No. 10-1455741. Among these triazolo pyrazine compounds, ABN401 is the most preferable. The IUPAC name of ABN401 is (S) -2 - ((6- (1 -methyl-1H-pyrazol-4-yl) -1 H- [1,2,3] triazolo [4,5- b] pyrazin- yl) methyl) -4 (5- (4-methylpiperazine-1-yl) methyl) phenyl) pyrimidine-2-yl) morpholin (description section).
PNG
media_image1.png
356
424
media_image1.png
Greyscale
The binder of the present invention may be selected from the group consisting of Microcrystalline Cellulose, Lactose monohydrate, Low-substituted hydroxypropylcellulose LH21, and Carboxymethyl cellulose sodium. And may include any one or more selected. The weight ratio of the triazolo pyrazine compound and the binder of the present invention may be 29:0.1 to 49:5 (description section).
The disintegrant of the present invention can be prepared by a process comprising the steps of: Microcrystalline Cellulose, Lactose monohydrate, Low-substituted hydroxypropylcellulose LH21 and Carboxymethyl cellulose sodium And the like. The weight ratio of the triazolo pyrazine compound of the present invention and the disintegrant may be from 29:0.1 to 49:5 (description section).
The composition of the present invention may further comprise an excipient. The excipients of the present invention may be selected from the group consisting of corn starch, lactose hydrate, microcrystalline cellulose 101, carboxymethyl cellulose sodium, croscarmellose sodium, Low-substituted hydroxypropylcellulose LH11, low-substituted hydroxypropyl cellulose LH21, crospovidone, povidone K30, povidone K90 (low-substituted hydroxypropyl cellulose LH11) Povidone K90, Colloidal Silicon Dioxide, Magnesium Stearate, Magnesium Silicate, Microcrystalline Cellulose (MCC) and Lactose monohydrate (LM) and the like. The weight ratio of the triazolo pyrazine compound of the present invention and the excipient may be from 29:50 to 49:70 (description section).
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claims 3 and 5 are objected to because of the following informalities: Applicant used the phrase “at least any one selected from the group consisting of” to recite the Markush lists of binders and disintegrants respectively in claims 2 and 4. However, Applicant uses different phrase “at least any one selected from” when reciting the list of disintegrants in claim 3 and the list of hyperproliferative disorder in claim 5 respectively. For consistency purpose, Applicant should use the common Markush recitation phrase “selected from the group consisting of” for all Markush recitations. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
Note: The claims are examined with respect to the elected species wherein sodium stearyl fumarate as the binder; sodium starch glycolate as the disintegrant; and colloidal silicon dioxide as the excipient.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (KR20190028903, IDS reference 6/15/23) in view of Al Husban et al. (WO 2017/182589, newly cited).
Applicants’ claims
Applicants claim a table formulation composition for the treatment of hyper proliferative disorders comprising a triazolopyrazine derivative and the components as recited in claim 1. Dependent claims thereof recite further limitations defining the binder, disintegrant, and excipient.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Kim et al. teach a rapid capsule composition containing a raw drug, an excipient, a binder and a granule prepared from a disintegrant. More particularly, the present invention relates to a triazolopyrimidine compound, a lactose monohydrate as an excipient, A low-substituted hydroxypropylcellulose LH21 (low-substituted hydroxypropylcellulose LH21) and a low-substituted hydroxypropylcellulose LH21 (low-substituted hydroxypropylcellulose LH21) as a disintegrant (abstract). The binder is added to increase the strength of the product by imparting elasticity and tackiness to the sample when the powder is formed in the fields of pharmaceuticals, catalysts and the like. In addition, the field of ceramics refers to a substance to be added to increase the strength of a product when the sample is sintered or formed, preferably to give a binding force to the drug to facilitate preparation of tablets and the like. In the present invention, ABN401, a solvothyrazine compound, and an excipient were tested for their stability. The disintegrant of the present invention is added for the purpose of promoting the disintegration of tablets, capsules, granules or the like in the digestive juices. Starch and carbonate, and was selected as an excipient having stability through the mutual stability test between ABN401, which is the most preferable triazolo pyrazine compound in the present invention, and an excipient. The excipient means that the drug is biocompatible in the body of the patient and helps to avoid side effects while forming the formulation together with the original drug. The excipient can be divided into various types depending on the role used in the preparation. Depending on the amount of the raw material, it may be added to the diluent or the weight of the filler to make the tablet an appropriate size, or a small-sized excipient, or a binding agent, a tablet or a granule, A disintegrant to promote disintegration of the formulation, a lubricant added to improve the fluidity of the granule and to prevent friction and sticking between particles, an adsorbent to assist in the absorption of the liquid raw material, And release control additives used in accordance with the hydrophilicity, hydrophobicity and pH dependency used. At this time, each excipient does not only serve as one of the excipients but also functions as a different function depending on the composition ratio contained in the formulation. The triazolo pyrazine compounds include, but are not limited to, triazolopyrazine derivatives and pharmaceutically acceptable salts thereof disclosed in Korean Patent No. 10-1455741. Among these triazolo pyrazine compounds, ABN401 is the most preferable. The IUPAC name of ABN401 is (S) -2 - ((6- (1 -methyl-1H-pyrazol-4-yl) -1 H- [1,2,3] triazolo [4,5- b] pyrazin- yl) methyl) -4 (5- (4-methylpiperazine-1-yl) methyl) phenyl) pyrimidine-2-yl) morpholin (description section).
PNG
media_image1.png
356
424
media_image1.png
Greyscale
The binder of the present invention may be selected from the group consisting of Microcrystalline Cellulose, Lactose monohydrate, Low-substituted hydroxypropylcellulose LH21, and Carboxymethyl cellulose sodium. And may include any one or more selected. The weight ratio of the triazolo pyrazine compound and the binder of the present invention may be 29:0.1 to 49:5 (description section).
The disintegrant of the present invention can be prepared by a process comprising the steps of: Microcrystalline Cellulose, Lactose monohydrate, Low-substituted hydroxypropylcellulose LH21 and Carboxymethyl cellulose sodium And the like. The weight ratio of the triazolo pyrazine compound of the present invention and the disintegrant may be from 29:0.1 to 49:5 (description section).
The composition of the present invention may further comprise an excipient. The excipients of the present invention may be selected from the group consisting of corn starch, lactose hydrate, microcrystalline cellulose 101, carboxymethyl cellulose sodium, croscarmellose sodium, Low-substituted hydroxypropylcellulose LH11, low-substituted hydroxypropyl cellulose LH21, crospovidone, povidone K30, povidone K90 (low-substituted hydroxypropyl cellulose LH11) Povidone K90, Colloidal Silicon Dioxide, Magnesium Stearate, Magnesium Silicate, Microcrystalline Cellulose (MCC) and Lactose monohydrate (LM) and the like. The weight ratio of the triazolo pyrazine compound of the present invention and the excipient may be from 29:50 to 49:70 (description section).
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Kim et al. do not specifically teach the incorporation of starch sodium glycolate and sodium stearyl fumarate in the composition. These deficiencies are cured by the teachings of Al Husban et al.
Al Husban et al. teach rapidly disintegrating oral dosage forms, more particularly to rapidly disintegrating tablets containing (1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-5 5-(2-hydroxyethoxy)cyclopentane-1,2-diol and a disintegrating excipient (see abstract). The tablets of the invention contain at least one disintegrating excipient. Said disintegrating excipient may be a single substance or it may be a mixture of substances (referred to herein as a disintegrating excipient pre-mix) wherein said mixture of substances functions as a disintegrant. In one embodiment, the disintegrating excipient is a fast oral disintegrating excipient. The use of a fast oral disintegrating excipient increases the rate of disintegration of the oral dosage form. Fast oral disintegrating excipients are excipients which are suitable for use in pharmaceutical and/or nutraceutical formulations and which enable the manufacture of tablets which have an oral disintegrating time of less than 3 minutes. It is preferred that the disintegrating excipients referred to in the embodiments disclosed herein are disintegrating excipient pre-mixes (see page 5, lines 8-17). Disintegrants that are suitable for use as disintegrating excipients in the tablets of the present invention include, but are not limited to, low-substituted hydroxypropyl cellulose, and. particularly, crospovidone, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, and mixtures thereof. Commercially available disintegrating excipient pre-mixes such as F-melt type C, F-melt type M, Ludiflash, GalenlQ, Prosolv and Pharmaburst may also be used in the tablets of the present invention (page 5, lines 19-24).
Al Husban et al. also teach in one embodiment, the tablets of the invention comprise one or more lubricants. In another embodiment, the tablets of the invention comprises one lubricant. Other suitable lubricants and additional excipients which may be used are described in Handbook of Pharmaceutical Excipients, 2nd Edition, American Pharmaceutical Association; The Theory and Practice of Industrial Pharmacy, 2nd Edition, Lachman, Leon, 1976; Pharmaceutical Dosage Forms: Tablets Volume 1 , 2nd Edition, Lieberman, Hebert A., et al, 1989; Modern Pharmaceutics, Banker, Gilbert and Rhodes, Christopher T, 1979; and Remington's Pharmaceutical Sciences, 15th Edition, 1975. Suitable lubricants include, for example, magnesium stearate, stearic acid, palmitic acid, calcium stearate, carnauba wax, hydrogenated vegetable oils, mineral oil, polyethylene glycols and sodium stearyl fumarate. In one embodiment, the lubricant is selected from magnesium stearate and sodium stearyl fumarate. In another embodiment, the lubricant is sodium stearyl fumarate (see page 9, lines 19-31). Al Husban et al. teach that its experimental results indicated that less of both crospovidone and sodium stearyl fumarate gives shorter disintegration time. The amount of silica did not significantly affect the disintegration time but both sodium stearyl fumarate and silica improved the flowability. Increased amount of both sodium stearyl fumarate and crospovidone gave slightly faster dissolution rate, although all complied with the preferred dissolution thresholds of Q=70 at 45 min and Q=75 at 60 min (see page 42, lines 4-9).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant invention to modify the teachings of Kim et al. by incorporating sodium starch glycolate and sodium stearyl fumarate because Al Husban et al. teach rapidly disintegrating oral dosage forms, more particularly to rapidly disintegrating tablets containing (1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4- difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]-triazolo[4,5-d]pyrimidin-3-yl]-5 5-(2-hydroxyethoxy)cyclopentane-1,2-diol and a disintegrating excipient (see abstract). Disintegrants that are suitable for use as disintegrating excipients in the tablets of the present invention include, but are not limited to, low-substituted hydroxypropyl cellulose, and. particularly, crospovidone, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, and mixtures thereof. Commercially available disintegrating excipient pre-mixes such as F-melt type C, F-melt type M, Ludiflash, GalenlQ, Prosolv and Pharmaburst may also be used in the tablets of the present invention (page 5, lines 19-24). The tablets of the invention contain at least one disintegrating excipient. Said disintegrating excipient may be a single substance or it may be a mixture of substances (referred to herein as a disintegrating excipient pre-mix) wherein said mixture of substances functions as a disintegrant. In one embodiment, the disintegrating excipient is a fast oral disintegrating excipient. One of ordinary skill in the art would have been motivated to do so because Al Husban et al. teach that the use of a fast oral disintegrating excipient (such as sodium starch glycolate) increases the rate of disintegration of the oral dosage form. Fast oral disintegrating excipients are excipients which are suitable for use in pharmaceutical and/or nutraceutical formulations and which enable the manufacture of tablets which have an oral disintegrating time of less than 3 minutes. It is preferred that the disintegrating excipients referred to in the embodiments disclosed herein are disintegrating excipient pre-mixes (see page 5, lines 8-17). Additionally, it would have been prima facie obvious to substitute the disintegrants taught by Kim et al. with sodium starch glycolate because the disintegrants are functionally equivalent as disintegrants. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.)
Furthermore, it would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant invention to modify the teachings of Kim et al. by incorporating sodium stearyl fumarate because Al Husban et al. also teach in one embodiment, the tablets of the invention comprise one or more lubricants. In another embodiment, the tablets of the invention comprises one lubricant. Other suitable lubricants and additional excipients which may be used are described in Handbook of Pharmaceutical Excipients, 2nd Edition, American Pharmaceutical Association; The Theory and Practice of Industrial Pharmacy, 2nd Edition, Lachman, Leon, 1976; Pharmaceutical Dosage Forms: Tablets Volume 1 , 2nd Edition, Lieberman, Hebert A., et al, 1989; Modern Pharmaceutics, Banker, Gilbert and Rhodes, Christopher T, 1979; and Remington's Pharmaceutical Sciences, 15th Edition, 1975. Suitable lubricants include, for example, magnesium stearate, stearic acid, palmitic acid, calcium stearate, carnauba wax, hydrogenated vegetable oils, mineral oil, polyethylene glycols and sodium stearyl fumarate. In one embodiment, the lubricant is selected from magnesium stearate and sodium stearyl fumarate. In another embodiment, the lubricant is sodium stearyl fumarate (see page 9, lines 19-31). One of ordinary skill in the art would have been motivated to do so because Al Husban et al. teach that its experimental results indicated that less of both crospovidone and sodium stearyl fumarate gives shorter disintegration time. The amount of silica did not significantly affect the disintegration time but both sodium stearyl fumarate and silica improved the flowability. Increased amount of both sodium stearyl fumarate and crospovidone gave slightly faster dissolution rate, although all complied with the preferred dissolution thresholds of Q=70 at 45 min and Q=75 at 60 min (see page 42, lines 4-9). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.)
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Kim et al. and Al Husban et al. because both references teach triazolo derivatives containing tablet compositions. Furthermore, in the case where the claimed ratios of the components as recited in claim 1"overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955).
As Applicant’s claims 1-5 are drawn to a composition of matter, the phrase “for the treatment of hyper proliferative disorder” in claim 1 and also the list of hyper proliferative disorder types recited in claim 5 are considered to be an intended use of the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Moreover, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIGABU KASSA whose telephone number is (571)270-5867. The examiner can normally be reached on 8 AM-5 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TIGABU KASSA/Primary Examiner, Art Unit 1619