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 .
Claim Status
Claims 32 and 43 are cancelled.
Claims 8-11, 24-26, and 33-43 are withdrawn.
Claims 1-7, 12-23, 27-31, and 44 are being examined herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. EP23156619.1 and EP23156485.7 filed on 02/14/2023 and EP 23383302.9 filed on 12/15/2023.
Acknowledgment is also made of applicant’s claim for benefit of provisional 63/476715 and application No. 63/476,733, both filed on 12/22/2022.
Information Disclosure Statement
The IDS filed on 02/24/2023 have been fully considered with all the references. IDS filed on 01/21/2026 have been considered, however NPL reference cite No. 3, 4, 6, and 7 were not considered because copies of the references were not provided. See the attached PTO 1449 forms.
Election/Restrictions
Applicant’s election without traverse of the invention of Group 1, i.e., claims 1-31 and 44 and single specific species in claims 5-12 and 21-27, in the reply filed on 01/21/2026 is acknowledged.
Claims 8-11, 24-26, and 33-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention group and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/21/2026.
Applicant has elected hydroxypropyl methylcelluloses and esters thereof for the specific species of polymer or polymer/copolymer, which encompasses claims 5-7 and 12. Applicant also elected mixture of microcrystalline cellulose and mannitol for the specific species of excipients, which encompasses claims 22, 23, 27, and 30.
Claims 22, 23, 27, and 30 are readable on elected species and subsequently claims 1-7, 12-23, 27-31, and 44 are being examined on merits herein.
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.
Claim 3 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 upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites polymer of claim 2 is enteric or non-enteric. Claim 3 does not further limit the limitations of claim 2 which it depends on since all the polymers would be either enteric or non-enteric. 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 § 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 (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 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.
Claims 1-6, 12-17, 21, 22, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) in view of Wilding et.al. (WO2021213800A1, effectively filed 04/24/2020 and published 10/28/2021) and evidenced by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105).
Fry teaches a solid dispersion comprising HER2 inhibitor compound N4-(4-([1,2,4] triazolo[1,5-a] pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5 dihydrooxazol-2-yl) quinazoline-4,6-diamine which is structurally similar to the instantly claimed compound (1) and a dispersion polymer ([0039], [0057], [0060], and claim1), which reads on instant claim 1. The HER2 inhibitor compound taught by Fry is structurally similar to claimed HER2 inhibitor compound as they both have multiple aromatic rings (fused aromatic ring system attached to phenyl group through amine linkage and the phenyl group is attached to benzimidazole type ring system) as shown in the structures below. The fused aromatic ring Quinazoline (A) in the HER2 inhibitor compound taught by Fry, is attached to phenyl ring (B) through amine linkage and the phenyl ring is further attached to the pyridine ring fused with imidazole ring (C) through ether linkage (see figures below). The fused aromatic ring system (X) of the claimed HER2 inhibitor compound is attached to phenyl ring (Y) which is further attached to benzimidazole ring system (Z) through ether linkage (see figures below). The quinazoline (A) of the HER2 inhibitor compound taught by Fry is bioisostere of the fused aromatic ring system (X) of claimed HER2 inhibitor compound. Similarly, the pyridine ring fused with imidazole ring (C) in the HER2 inhibitor compound of Fry is bioisostere of the benzimidazole ring (Z) of the instantly claimed HER2 inhibitor compound (see figures below). Moreover, the phenyl ring (B) of Fry’s HER2 inhibitor compound is identical to the phenyl ring (Y) of the instantly claimed HER2 inhibitor compound.
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HER2 inhibitor (Fry et.al.) Claimed compound (1)
Fry teaches hydroxypropyl methylcellulose acetate succinate (HPMCAS) in its embodiments ([0052]) which reads on dispersion carrier in instant claims 2, 5-6, and 12. HPMCAS as taught by Fry is an enteric polymer as evidenced by Mounica (Pg.16, lines 5-8) which reads on instant claims 3 and 4. Fry further teaches that the structurally similar HER2 inhibitor compound in the solid dispersion is amorphous (claims 2 and 6) which reads on instant claim 13. Fry also teaches in one of its embodiments that the structurally similar HER2 inhibitor compound can be about 50% by weight relative to the dispersion polymer ([0062], lines 7-13), which reads as 50% by weight of structurally similar HER2 inhibitor compound and 50% by weight of dispersion polymer. The amount of structurally similar HER2 inhibitor compound of 50% by weight as taught by Fry anticipates the genus of claimed amount range of 25 wt% to 75 wt% of compound (1) in the instant claim 14 and the 50% by weight of dispersion polymer taught by Fry anticipates the genus of claimed amount range of 25 wt% to 75 wt% of dispersion polymers in the instant claim 15. The relative amount of 50% by weight structurally similar HER2 inhibitor compound and 50% by weight of dispersion polymer taught by Fry is a weight ratio of 1:1 which reads on instant claims 16 and 17. Fry further teaches a pharmaceutical composition comprising of solid dispersion of structurally similar HER2 inhibitor compound and pharmaceutically acceptable excipients (claim 7), which reads on instant claim 21. Fry also teaches their pharmaceutical compositions in its embodiments, comprising solid dispersion of structurally similar HER2 inhibitor compound and pharmaceutically acceptable excipients such as 1 to 10 wt% of disintegrant ([0121]), 15 to 25 wt% of osmogen ([0122]), 0.1 to 3 wt% of glidant ([0123]), 0.1 to 3 wt% of lubricant ([0124]), and 10 to 25 wt% of fillers ([0125]) which is obvious over instant claims 22 and 28. Fry teaches that the pharmaceutical composition can be in form of tablet ([0198] and [0252]) which reads on instant claim 29. Fry also teaches exemplary pharmaceutical composition in form of tablet containing solid dispersion, microcrystalline cellulose ([0252]) and further tablets are coated with 3% OPADRY II 85F92727 ([0253]), which reads on instant claim 30.
Fry does not teach the HER2 inhibitor is the claimed compound (1) of the instant claim 1 as discussed above. However, as discussed above, Fry does teach structurally similar HER2 inhibitor compound which has quinazoline ring (A) which is bioisostere of the fused aromatic ring system (X) of claimed HER2 inhibitor compound the benzimidazole ring (C), attached to the phenyl ring through amine linkage and the phenyl ring is further attached to pyridine ring fused with imidazole ring (C) which is bioisostere of the benzimidazole ring (Y) of the instantly claimed compound. Further, the HER2 inhibitor compound of Fry has side group attached to quinazoline ring is different than the side group in the claimed HER2 inhibitor compound.
Wilding teaches HER2 inhibitor compound (1) recited in the instant claim 1 (Pg.10, structure I-01) and also teaches pharmaceutical composition comprising the compound (1) of instant claim 1 and pharmaceutically acceptable excipient (Pg.17, lines 10-13).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the HER2 inhibitor compound in the solid dispersion comprising dispersion carrier as taught by Fry with the compound I-01 taught by Wilding which is also a HER2 inhibitor, and arrive at the claimed invention. A skilled artisan would have been motivated to prepare solid dispersion of the HER2 inhibitor compound I-01 taught by Wilding according to Fry because Fry teaches preparation of solid dispersion of the HER2 inhibitor compound of formula N4-(4-([1,2,4] triazolo [1,5-α] pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl) quinazoline-4,6-diamine, which is structural analog of HER2 inhibitor compound taught by Wilding. The HER2 inhibitor compound taught by Fry is structurally similar because of the reasons discussed above.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Fry has demonstrated preparation of solid dispersion of HER2 inhibitor is routine and known in the art. Also, the HER2 inhibitor compound of Fry is structurally similar to the HER2 inhibitor compound taught by Wilding and both compounds are used for treating hyperproliferative disease in a mammal.
Claims 1-6, 7, 12-17, 21, 22, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) in view of Wilding et.al. (WO2021213800A1, effectively filed 04/24/2020 and published 10/28/2021) as evidenced by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105) as applied to Claims 1-6, 12-17, 21, 22, and 28-30 above, and in further view of Hao et.al. (Application of HPMC HME polymer as hot melt extrusion carrier in carbamazepine solid dispersion. Drug Development and Industrial Pharmacy, 46(12), 1911–1918, (2020).
Fry and Wilding collectively fails to explicitly teach that the dispersion carrier hydroxypropyl methylcelluloses and esters thereof are selected from the group of hydroxypropyl methylcellulose acetate succinate and hot melt extrusion-grade hydroxypropyl methylcellulose.
Hao teaches that hydroxypropyl methylcellulose is widely used polymers in the preparations of solid dispersions (Pg.2, lines 33-34). Hao further teaches use of hot melt extrusion-grade hydroxypropyl methylcellulose polymer as a dispersion carrier in the solid dispersion (Abstract, lines 1-2). Hao also teaches that hot melt extrusion-grade hydroxypropyl methylcellulose polymer exhibits low viscosity and very low hygroscopicity (Pg.8, lines 35-45). Hao further teaches that low viscosity can prevent gelatinization during capsule dissolution and improve bioavailability of poorly soluble drugs (Pg.8, lines 5-8 and 35-40) and low hygroscopicity of polymer improves stability of amorphous drugs and prevent conversion to crystalline forms (Pg.8, lines 25-34 and 43-45).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to use hot melt extrusion-grade hydroxypropyl methylcellulose polymers as taught by Hao in the solid dispersion comprising HER2 inhibitor compound and dispersion carrier collectively taught by Fry and Wilding, and arrive at the claimed invention. It would have been obvious for a skilled artisan to add the hot melt extrusion-grade hydroxypropyl methylcellulose acetate succinate in the solid dispersion comprising HER2 inhibitor compound (1) of Wilding prepared according to Fry.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Hao have demonstrated use of hot melt extrusion-grade hydroxypropyl methylcellulose is known in the art and has advantages of improving bioavailability and long-term stability of amorphous drugs.
Claims 1, 2, 5-6, 12-17, 21, 22, 23, 27, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) in view of Wilding et.al. (WO2021213800A1, effectively filed 04/24/2020 and published 10/28/2021) and evidence by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105) as applied to claims 1-6, 12-17, 21, 22, and 28-30 above and in further view of Sherif et.al. (Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation. Pharm Dev Technol. 2010 Jul-Aug;15(4):339-45. doi: 10.3109/10837450903229065. PMID: 20088677.).
Fry and Wilding collectively fails to explicitly teach the fillers selected from the group consisting of mixture of microcrystalline cellulose and mannitol mixtures as elected by applicant in the instant claim 23 and mannitol or microcrystalline cellulose as elected by the applicant in the instant claim 27. However, Fry teaches use of lactose as a filler ([00076] and [000149]).
Sherif teaches that pharmaceutical formulations based on microcrystalline cellulose and lactose as fillers are very commonly used, however use of lactose as fillers should be avoided because it could chemically react with drugs containing amine moiety (Pg.2, Introduction, lines 1-13). Sherif also teaches that microcrystalline cellulose could be used alone as it is the most widely used pharmaceutical excipient due to its desirable attributes or could be used along with other fillers like mannitol (Pg.2, Introduction, lines 1-2). Sherif further teaches that when used alone, the excellent compactibility of microcrystalline cellulose could be significantly reduced upon wet granulation (Pg.2, Introduction, lines 4-8). Sherif teaches that use of mannitol and microcrystalline cellulose as fillers in the pharmaceutical formulation (tablet) can increase compactibility of the final granulation, reduce compression speed sensitivity and decrease the susceptibility of the formulation to hardness loss upon storage (Pg.2, Abstract, lines 8-11).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to try microcrystalline cellulose and mannitol as fillers in the pharmaceutical formulation taught by Fry and modified by switching HER2 inhibitor compound of Fry with HER2 inhibitor compound taught by Wilding and arrive at the claimed invention in the instant claims 23, and 27. A skilled artisan would have been motivated to use microcrystalline cellulose and mannitol as fillers in the pharmaceutical composition taught by Fry because of the advantages taught by Sherif above.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications because Fry teaches use of microcrystalline cellulose as an excipient in the pharmaceutical formulations and Sherif teaches that microcrystalline cellulose and mannitol are very common fillers used in pharmaceutical industry for tablet formulations with several advantages over using microcrystalline cellulose alone as discussed above.
Claims 1, 2, 5-6, 12-17, 18-20, 21, 22, 28-30, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) in view of Wilding et.al. (WO2021213800A1, effectively filed 04/24/2020 and published 10/28/2021) as evidence by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105) applied to claims 1-6, 12-17, 21, 22, and 28-30 above and further evidenced by Haitham Alrabiah (Chapter Two - Levetiracetam, Profiles of Drug Substances, Excipients and Related Methodology, Academic Press, Volume 44, 2019, Pages 167-204, ISSN 1871-5125, ISBN 9780128171653) and Ding. et al. (Differential Scanning Calorimetry (DSC) in Solid-State Characterization of Solid Dispersions: A Practical Guide. AAPS Pharm Sci Tech 27, 20 (2026)).
Fry and Wilding collectively fail to explicitly teach the solid dispersion is characterized by having an x-ray powder diffractogram comprising no diffraction peak at 2-theta angles equal or below 40.0°, when measured at a temperature in the range of from 20 to 30 °C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A as recited in the instant claim 18. Fry does not explicitly teach solid dispersion is characterized by having a differential scanning calorimetry curve comprising a single glass transition temperature signal, when measured with modulated differential scanning calorimetry with a modulation amplitude of 1 °C/min and a heating rate of 3.0 °C/min as recited in the instant claim 19 and further the single glass transition temperature signal is in the range of from 90 to 190 °C as recited in the instant claim 20. Fry does not explicitly teach pharmaceutical composition is characterized by having an x-ray powder diffractogram comprising no diffraction peak at 2-theta angles equal or below 6.5°, when measured at a temperature in the range of from 20 to 30°C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A as recited in the instant claim 31.
For claims 18 and 31
X-ray powder diffraction (XRPD) measurements are known in the art and commonly used for characterizing the crystalline forms of active pharmaceutical ingredients as evidenced by Haitham (Pg.171, 4.2 X-ray power diffraction pattern). The absence of diffraction peaks in the x-ray powder diffractogram at 2-theta angles equal or below 40.0°, when measured at a temperature in the range of from 20 to 30 °C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A, is an indication of solid dispersions being in amorphous form as disclosed in the instant specification (Pg.53, lines 2-9). Therefore, the XRPD characterization of the dispersion prepared by switching the HER2 inhibitor compound in the dispersion taught by Fry with HER2 inhibitor compound I-01 taught by Wilding, would exhibit same characteristics (absence of diffraction peaks in diffractogram) as claimed in the instant claim 18. Similarly, pharmaceutical composition of HER2 inhibitor compound I-01 of Wilding prepared according to Fry as discussed above, would show absence of diffraction peaks in X-ray powder diffractogram as claimed in the instant claim 31.
For claims 19 and 20
Differential scanning calorimetry (DSC) is known in the art and routinely used for characterizing amorphous and crystalline solid dispersions by understanding the phase transitions as evidenced by Ding (Abstract). The single glass transition temperature signal in the differential scanning calorimetry curve obtained from modulated differential scanning calorimetry (MDSC) characterization, indicates the measured solid dispersion is single phase comprising amorphous compound as evidenced by instant specification (Pg.58, lines 14-17). Therefore, solid dispersion of HER2 inhibitor compound prepared according to Fry by substituting HER2 inhibitor compound of Fry with HER2 inhibitor compound I-01 taught by Wilding, would be expected to produce single glass transition temperature signal in the range of 90 to 190 ̊C when characterized by MDSC as recited in the instant claims 19 and 20.
Claims 1, 2, 5-6, 12-17, 21, 22, 28-30 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) in view of Wilding et.al. (WO2021213800A1, effectively filed 04/24/2020 and published 10/28/2021) as evidence by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105) applied to claims 1-6, 12-17, 21, 22, and 28-30 above in further view of Johnson (CA2648533A1, published 11/08/2007).
Fry and Wilding collectively fails to teach A kit comprising the solid dispersion and a container to contain said solid dispersion or pharmaceutical composition and a desiccant as recited in the instant claim 44.
Johnson teaches fucoidan (reads as solid drug) in form of capsules can be supplied in a kit comprising sealed container containing capsules (Pg.19, lines 1-6). Johnson also teaches that commonly employed form of packaging of pharmaceuticals can include desiccants (Pg.17, lines 6-9).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to provide the pharmaceutical composition of tablet form prepared according to Fry using HER2 inhibitor compound of Wilding, in a kit comprising container to contain pharmaceutical composition and a desiccant as taught by Johnson and arrive at the claimed invention.
It would have been obvious for a skilled artisan to supply pharmaceutical composition in Kit for administration because Johnson demonstrated supplying pharmaceutical compositions comprising solid dispersions in a kit is routine and known in the art. Furthermore, supply pharmaceutical composition in a kit format including everything needed to administer the composition to the patient provides many benefits. For example, Kitting allows maintaining consistency and quality of medication across all the patients; simplified and easy administration of the medication; streamlining process of preparing/delivering medications, reducing time and resources required for each patients visit; and supplying desiccant in the kit helps maintain integrity of the medication by preventing moisture related degradation and contamination.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-7, 12-23, 27-31, and 44 provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 2, 3, 4, 5, 6, 10, 13, 14, and 42 of co-pending Application No. 19/141,459 (reference application) in view of Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017), Hao et.al. (Application of HPMC HME polymer as hot melt extrusion carrier in carbamazepine solid dispersion. Drug Development and Industrial Pharmacy, 46(12), 1911–1918, (2020), Sherif et.al. (Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation. Pharm Dev Technol. 2010 Jul-Aug;15(4):339-45. doi: 10.3109/10837450903229065. PMID: 20088677.), Johnson (CA2648533A1, published 11/08/2007) and as evidenced by Haitham Alrabiah (Chapter Two - Levetiracetam, Profiles of Drug Substances, Excipients and Related Methodology, Academic Press, Volume 44, 2019, Pages 167-204, ISSN 1871-5125, ISBN 9780128171653) and Ding. et al. (Differential Scanning Calorimetry (DSC) in Solid-State Characterization of Solid Dispersions: A Practical Guide. AAPS Pharm Sci Tech 27, 20 (2026)).
Although the claims at issue are not identical, they are not patentably distinct from each other because US’459 teaches method of treatment of cancer by using solid dispersion comprising compound (1) and a pharmaceutically acceptable dispersion carrier claimed in the instant application.
The solid dispersion comprising compound (1) and a pharmaceutically acceptable dispersion carrier claimed in the method of claims 1 and 2 of the reference co-pending patent application US’459 reads on instant Claim 1. The polymer dispersion carrier in the method of claim 3 of the US’459 reads on instant Claim 2. The enteric or non-enteric polymer in the method of claim 4 of US’459 reads on instant claim 3 and obvious over instant claim 5. The pharmaceutically acceptable dispersion carrier polymer selected from the group of a hydroxypropyl methylcellulose in the method of claim 5 of US’459 reads on instant Claim 5. The dispersion polymer selected from group consisting of hydroxypropyl methylcellulose acetate succinate as claimed in the method of claim 5 of US’459 reads on the elected species of dispersion polymer in the instant claims 6, 7, and 12. The amorphous compound claimed in the method of claim 10 of US’459 reads on invention of instant claim 13. The amount range of 25 wt% to 75 wt% of compound (1) and the amount range of 25 wt% to 75 wt% of pharmaceutically acceptable dispersion carrier, based on total of 100 wt% of the solid dispersion claimed in the method of claim 11 of US’459 anticipates the amounts of compound (1) in instant claim 14 and the dispersion carrier claimed in the instant claim 15. The weight ratio of compound (1) to the pharmaceutically acceptable dispersion carrier in the solid dispersion of 1:1 to 1:3 claimed in the method of claim 13 of US’459 reads on instant claim 16 and obvious over weight ratio of compound (1) to the pharmaceutically acceptable dispersion carrier in the solid dispersion of 1:1 of instant claim 17. The solid dispersion characterization claimed in the method of claim 14 of US’459 reads on instant claim 18. The pharmaceutical composition comprising a solid dispersion of compound (1) and a pharmaceutically acceptable excipients claimed in the method of claims 15 and 42 of US’459, reads on the instant claim 21.
US’459 differs from instantly claimed invention in that it does not claim hydroxypropyl methylcelluloses and esters thereof are selected from the group consisting of hydroxypropyl methylcellulose acetate succinate and hot melt extrusion-grade hydroxypropyl methylcellulose as recited in the instant claim 7. US’459 does not claim the solid dispersion, characterized by having a differential scanning calorimetry curve comprising a single glass transition temperature signal, when measured with modulated differential scanning calorimetry with a modulation amplitude of 1 QC/min and a heating rate of 3.0 QC/min as recited in the instant claim 19 and further the single glass transition temperature signal is in the range of from 90 to 190 QC as recited in the instant claim 20. US’459 does not claim pharmaceutically acceptable excipients in the pharmaceutical composition are fillers as elected by the applicant in the instant claim 22 and further fillers are mixture of microcrystalline and mannitol as elected by the applicant in the instant claim 23. US’459 also does not claim pharmaceutical composition, wherein the one or more pharmaceutically acceptable excipients comprise mannitol and microcrystalline cellulose as elected by the applicant in the instant claim 27. US’459 does not claim the pharmaceutical composition based on a total weight of 100 wt% of the pharmaceutical composition, comprises: 25 wt% to 65 wt% of the solid dispersion and /or 25 wt% to 65 wt% of fillers and/or 4 wt% to 10 wt% of disintegrant and/or 1 wt% to 2 wt% of glidant and/or 1 wt% to 2 wt% of lubricant and/or optionally 2 wt% to 5 wt% of coating agent, as recited in the instant claim 28. US’459 does not claim pharmaceutical composition is in the form of a tablet, of granules or of a capsule as recited in the instant claim 29. US’459 does not claim the pharmaceutical composition comprising (i) a tablet core comprising the solid dispersion, mannitol, and microcrystalline cellulose; and (ii) a film coating, as recited in the instant claim 30. US’459 does not claim the pharmaceutical composition characterized by having an x-ray powder diffractogram comprising no diffraction peak at 2-theta angles equal or below 6.5°, when measured at a temperature in the range of from 20 to 30°C and with Cu-Ka radiation having a wavelength of 1.54056 Å or 1.54184 Å as recited in the instant claim 31. US’459 does not claim a kit comprising: the solid dispersion; and a container to contain solid dispersion or pharmaceutical composition; and a desiccant as recited in the instant claim 44.
For claim 7
Hao teaches that hydroxypropyl methylcellulose is widely used polymers in the preparations of solid dispersions (Pg.2, lines 33-34). Hao further teaches use of hot melt extrusion-grade hydroxypropyl methylcellulose polymer as a dispersion carrier in the solid dispersion (Abstract, lines 1-2). Hao also teaches that hot melt extrusion-grade hydroxypropyl methylcellulose polymer exhibits low viscosity and very low hygroscopicity (Pg.8, lines 35-45). Hao further teaches that low viscosity can prevent gelatinization during capsule dissolution and improve bioavailability of poorly soluble drugs (Pg.8, lines 5-8 and 35-40) and low hygroscopicity of polymer improves stability of amorphous drugs and prevent conversion to crystalline forms (Pg.8, lines 25-34 and 43-45).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to use hot melt extrusion-grade hydroxypropyl methylcellulose polymers as taught by Hao in the solid dispersion claimed by US’459 and arrive at the claimed invention. It would have been obvious for a skilled artisan to add the hot melt extrusion-grade hydroxypropyl methylcellulose acetate succinate in the solid dispersion of US’459 because Hao provides solution to potential problems such as poor stability and bioavailability of amorphous drugs.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Hao have demonstrated use of hot melt extrusion-grade hydroxypropyl methylcellulose is known in the art and has advantages of improving bioavailability and long-term stability of amorphous drugs.
For claims 22, and 28-30
Fry teaches pharmaceutical compositions in its embodiments, comprising solid dispersion of structurally similar HER2 inhibitor compound and pharmaceutically acceptable excipients such as 1 to 10 wt% of disintegrant ([0121]), 15 to 25 wt% of osmogen ([0122]), 0.1 to 3 wt% of glidant ([0123]), 0.1 to 3 wt% of lubricant ([0124]), and 10 to 25 wt% of fillers ([0125]) which is obvious over instant claims 22 and 28. Fry teaches that the pharmaceutical composition can be in form of tablet ([0198] and [0252]) which reads on instant claim 29. Fry also teaches exemplary pharmaceutical composition in form of tablet containing solid dispersion, microcrystalline cellulose ([0252]) and further tablets are coated with 3% OPADRY II 85F92727 ([0253]), which reads on instant claim 30.
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to modify pharmaceutical composition of US’459 by selecting pharmaceutically acceptable excipients and the wt % of the excipients as taught by Fry and arrive at the claimed invention. It would have been obvious for a skilled artisan to further prepare the pharmaceutical composition in the form of tablet comprising solid dispersion of compound (1) of US’459, microcrystalline cellulose, and a tablet coating as guided by Fry.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Fry demonstrates that pharmaceutical compositions of solid dispersion of structurally similar HER2 inhibitor compounds and formulation of such compositions in tablet form is routine and known in the art.
For claim 23 and 27
Sherif teaches that pharmaceutical formulations based on microcrystalline cellulose and lactose as fillers are very commonly used, however use of lactose as fillers should be avoided because it could chemically react with drugs containing amine moiety (Pg.2, Introduction, lines 1-13). Sherif also teaches that microcrystalline cellulose could be used alone as it is the most widely used pharmaceutical excipient due to its desirable attributes or could be used along with other fillers like mannitol (Pg.2, Introduction, lines 1-2). Sherif further teaches that when used alone, the excellent compactibility of microcrystalline cellulose could be significantly reduced upon wet granulation (Pg.2, Introduction, lines 4-8). Sherif teaches that use of mannitol and microcrystalline cellulose as fillers in the pharmaceutical formulation (tablet) can increase compactibility of the final granulation, reduce compression speed sensitivity and decrease the susceptibility of the formulation to hardness loss upon storage (Pg.2, Abstract, lines 8-11).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to try microcrystalline cellulose and mannitol as fillers as taught by Sherif, in the pharmaceutical formulation taught by US’459 and arrive at the claimed invention in the instant claims 23, and 27. A skilled artisan would have been motivated to use microcrystalline cellulose and mannitol as fillers in the pharmaceutical composition taught by US’459 because of the advantages taught by Sherif above.
A person of ordinary skill in the art would have reasonable expectation of success of using mannitol and microcrystalline cellulose as fillers in the pharmaceutical composition of US’459 because Sherif demonstrates that microcrystalline cellulose and mannitol are very common fillers used in pharmaceutical industry for tablet formulations with several advantages over using microcrystalline cellulose alone as discussed above.
For claim 44
Johnson teaches fucoidan (reads as solid drug) in form of capsules can be supplied in a kit comprising sealed container containing capsules (Pg.19, lines 1-6). Johnson also teaches that commonly employed form of packaging of pharmaceuticals can include desiccants (Pg.17, lines 6-9).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to provide the pharmaceutical composition of US’459 in a kit comprising container to contain pharmaceutical composition and a desiccant as taught by Johnson and arrive at the claimed invention.
It would have been obvious for a skilled artisan to supply pharmaceutical composition in Kit for administration because Johnson demonstrated supplying pharmaceutical compositions comprising solid dispersions in a kit is routine and known in the art. Furthermore, supply pharmaceutical composition in a kit format including everything needed to administer the composition to the patient provides many benefits. For example, Kitting allows maintaining consistency and quality of medication across all the patients; simplified and easy administration of the medication; streamlining process of preparing/delivering medications, reducing time and resources required for each patients visit; and supplying desiccant in the kit helps maintain integrity of the medication by preventing moisture related degradation and contamination.
For claim 31
X-ray powder diffraction (XRPD) measurements are known in the art and commonly used for characterizing the crystalline forms of active pharmaceutical ingredients as evidenced by Haitham (Pg.171, 4.2 X-ray power diffraction pattern). The absence of diffraction peaks in the x-ray powder diffractogram at 2-theta angles equal or below 40.0°, when measured at a temperature in the range of from 20 to 30 °C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A, is an indication of solid dispersions being in amorphous form as disclosed in the instant specification (Pg.53, lines 2-9). Therefore, the XRPD characterization of the pharmaceutical composition of US’459 would exhibit same characteristics (absence of diffraction peaks in diffractogram) as claimed in the instant claim 31.
For claims 19 and 20
Differential scanning calorimetry (DSC) is known in the art and routinely used for characterizing amorphous and crystalline solid dispersions by understanding the phase transitions as evidenced by Ding (Abstract). The single glass transition temperature signal in the differential scanning calorimetry curve obtained from modulated differential scanning calorimetry (MDSC) characterization, indicates the measured solid dispersion is single phase comprising amorphous compound as evidenced by instant specification (Pg.58, lines 14-17). Therefore, solid dispersion of compound (1) claimed in US’459 would be expected to produce single glass transition temperature signal in the range of 90 to 190 ̊C when characterized by MDSC as recited in the instant claims 19 and 20.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 13 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 36, 37, 38, and 39 of co-pending Application No. 18/544,537 (reference application) in view of Fry et.al. (US20170136022A1, PG-Pub published 05/18/2017) as evidenced by Mounica et.al. (A review on recent advances in enteric coating and enteric polymers, WJPR, Volume 7, Issue 2, 475-495. ISSN2277-7105), Sherif et.al. (Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation. Pharm Dev Technol. 2010 Jul-Aug;15(4):339-45. doi: 10.3109/10837450903229065. PMID: 20088677.),and Johnson (CA2648533A1, published 11/08/2007) as evidenced by Haitham Alrabiah (Chapter Two - Levetiracetam, Profiles of Drug Substances, Excipients and Related Methodology, Academic Press, Volume 44, 2019, Pages 167-204, ISSN 1871-5125, ISBN 9780128171653) and Ding. et al. (Differential Scanning Calorimetry (DSC) in Solid-State Characterization of Solid Dispersions: A Practical Guide. AAPS Pharm Sci Tech 27, 20 (2026)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims the compound (1) and preparing solid dispersion comprising compound (1) and a dispersion carrier.
Claims 36 and 38 of reference patent are directed to preparing solid dispersion comprising compound (1) of instant claim 1 and a pharmaceutically acceptable dispersion carrier recited in the instant claim 1. The dispersion comprising compound (1) in amorphous form claimed in the claims 37 and 39 of the reference patent reads on the instant claim 13.
US’537 differs from the instantly claimed invention in that it does not claim the dispersion carrier in the solid dispersion comprising compound (1) of instant claim 1, is a polymer as recited in the instant claim 2 and that polymer is enteric as recited in instant claims 3 and 4. US’537 does not claim the polymer is selected from group consisting of hydroxypropyl methylcelluloses and esters thereof as recited in instant claim 5 and further, hydroxypropyl methylcelluloses and esters thereof are selected from the group consisting of hydroxypropyl methylcellulose acetate succinate as recited in the instant claim 6. US’537 does not claim hydroxypropyl methylcelluloses and esters thereof are selected from the group consisting of hydroxypropyl methylcellulose acetate succinate and hot melt extrusion-grade hydroxypropyl methylcellulose as recited in the instant claim 7. US’537 does not claim dispersion polymer in the solid dispersion is hydroxypropyl methylcellulose acetate succinate as recited in the instant claim 12. US’537 does not claim the compound (1) in the solid dispersion is present in an amount in a range of from 25 wt% to 75 wt%, based on a total weight of 100 wt% of the solid dispersion as recited in the instant claim 14 and the pharmaceutically acceptable dispersion carrier in an amount in a range of 25 wt% to 75 wt%, based on a total weight of 100 wt% of the solid dispersion as recited in the instant claim 15. US’537 does not claim the solid dispersion, wherein the weight ratio of compound (1) : the pharmaceutically acceptable dispersion carrier in the solid dispersion is of approximately 1 : 1 to 1 : 3 as recited in the instant claim 16 and further narrowly claimed ratio of 1:1 as recited in the instant claim 17. US’537 does not claim the solid dispersion is characterized by having an x-ray powder diffractogram comprising no diffraction peak at 2-theta angles equal or below 40.0°, when measured at a temperature in the range of from 20 to 30 °C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A as recited in the instant claim 18. US’537 does not claim the solid dispersion, characterized by having a differential scanning calorimetry curve comprising a single glass transition temperature signal, when measured with modulated differential scanning calorimetry with a modulation amplitude of 1 QC/min and a heating rate of 3.0 QC/min as recited in the instant claim 19 and further the single glass transition temperature signal is in the range of from 90 to 190 QC as recited in the instant claim 20. US’537 further does not claim pharmaceutical composition comprising the solid dispersion of claimed compound (1) and a pharmaceutically acceptable excipients as recited in the instant claim 21. US’537 does not claim the pharmaceutically acceptable excipients in the pharmaceutical composition are fillers as elected by the applicant in the instant claim 22 and further fillers are mixture of microcrystalline and mannitol as elected by the applicant in the instant claim 23. Furthermore, US’537 does not claim, one or more pharmaceutically acceptable excipients in the pharmaceutical composition, comprises mannitol and microcrystalline cellulose as elected by the applicant in the instant claim 27. US’537 does not claim the pharmaceutical composition based on a total weight of 100 wt% of the pharmaceutical composition, comprises: 25 wt% to 65 wt% of the solid dispersion and /or 25 wt% to 65 wt% of fillers and/or 4 wt% to 10 wt% of disintegrant and/or 1 wt% to 2 wt% of glidant and/or 1 wt% to 2 wt% of lubricant and/or optionally 2 wt% to 5 wt% of coating agent, as recited in the instant claim 28. US’537 does not claim pharmaceutical composition is in the form of a tablet, of granules or of a capsule as recited in the instant claim 29. US’537 does not claim the pharmaceutical composition comprising (i) a tablet core comprising the solid dispersion, mannitol, and microcrystalline cellulose; and (ii) a film coating, as recited in the instant claim 30. US’537 does not claim the pharmaceutical composition characterized by having an x-ray powder diffractogram comprising no diffraction peak at 2-theta angles equal or below 6.5°, when measured at a temperature in the range of from 20 to 30°C and with Cu-Ka radiation having a wavelength of 1.54056 Å or 1.54184 Å as recited in the instant claim 31. US’537 does not claim a kit comprising: the solid dispersion; and a container to contain solid dispersion or pharmaceutical composition; and a desiccant as recited in the instant claim 44.
For claims 2-6, 12, 14-17, 21, 22, and 28-30
Fry teaches a solid dispersion comprising HER2 inhibitor compound N4-(4-([1,2,4] triazolo[1,5-a] pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5 dihydrooxazol-2-yl) quinazoline-4,6-diamine which is structurally similar to the instantly claimed compound (1) and a dispersion polymer ([0039], [0057], [0060], and claim1). Fry teaches hydroxypropyl methylcellulose acetate succinate (HPMCAS) in its embodiments ([0052]) which reads on dispersion carrier in instant claims 2, 5-6, and 12. HPMCAS as taught by Fry is an enteric polymer as evidenced by Mounica (Pg.16, lines 5-8) which reads on instant claims 3 and 4. Fry also teaches the structurally similar HER2 inhibitor compound in one of its embodiments can be about 50% by weight relative to the dispersion polymer ([0062], lines 7-13), which reads as 50% by weight of structurally similar HER2 inhibitor compound and 50% by weight of dispersion polymer. The amount of structurally similar HER2 inhibitor compound and dispersion polymer of 50% by weight as taught by Fry anticipates the genus of claimed amount range of 25 wt% to 75 wt% of compound I and dispersion polymer in the instant claims 14 and 15. The relative amount of 50% by weight structurally similar HER2 inhibitor compound and 50% by weight of dispersion polymer taught by Fry is a weight ratio of 1:1 which reads on instant claims 16 and 17. Fry further teaches a pharmaceutical composition comprising of solid dispersion of structurally similar HER2 inhibitor compound and pharmaceutically acceptable excipients (claim 7), which reads on instant claim 21. Fry also teaches their pharmaceutical compositions in its embodiments, comprising solid dispersion of structurally similar HER2 inhibitor compound and pharmaceutically acceptable excipients such as 1 to 10 wt% of disintegrant ([0121]), 15 to 25 wt% of osmogen ([0122]), 0.1 to 3 wt% of glidant ([0123]), 0.1 to 3 wt% of lubricant ([0124]), and 10 to 25 wt% of fillers ([0125]) which is obvious over instant claims 22 and 28. Fry teaches that the pharmaceutical composition can be in form of tablet ([0198] and [0252]) which reads on instant claim 29. Fry also teaches exemplary pharmaceutical composition in form of tablet containing solid dispersion, microcrystalline cellulose ([0252]) and further tablets are coated with 3% OPADRY II 85F92727 ([0253]), which reads on instant claim 30.
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to modify the solid dispersion comprising instantly claimed compound (1) and a pharmaceutically acceptable dispersion carrier claimed in US’537 according to Fry by selecting HPMCAS as a dispersion carrier and further prepare the pharmaceutical composition by adding pharmaceutically acceptable excipients taught by Fry and arrive at the claimed invention. It would have been obvious for a skilled artisan to further prepare the in the form of tablet comprising solid dispersion of compound (1) of US’537, microcrystalline cellulose, and a tablet coating as guided by Fry, for administering medication to patients.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Fry demonstrates that pharmaceutical compositions of solid dispersion of structurally similar HER2 inhibitor compounds and formulation of such compositions in tablet form is routine and known in the art.
For claim 23 and 27
Sherif teaches use of mannitol and microcrystalline cellulose as fillers in the pharmaceutical formulation (tablet) can increase compactibility of the final granulation, reduce compression speed sensitivity and decrease the susceptibility of the formulation to hardness loss upon storage (Abstract, lines 8-11). Sherif also teaches that microcrystalline cellulose could be used alone as it is the most widely used pharmaceutical excipient due to its desirable attributes or could be used along with other fillers like mannitol (Introduction, lines 1-2). Sherif further teaches that when used alone, the excellent compactibility of microcrystalline cellulose could be significantly reduced upon wet granulation (Introduction, lines 4-8).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to try microcrystalline cellulose and mannitol as fillers as taught by Sherif, in the pharmaceutical formulation taught by US’537 and arrive at the claimed invention in the instant claims 23, and 27. A skilled artisan would have been motivated to use microcrystalline cellulose and mannitol as fillers in the pharmaceutical composition taught by US’537 because of the advantages taught by Sherif above.
A person of ordinary skill in the art would have reasonable expectation of success of using mannitol and microcrystalline cellulose as fillers in the pharmaceutical composition of US’537 because Sherif demonstrates that microcrystalline cellulose and mannitol are very common fillers used in pharmaceutical industry for tablet formulations with several advantages over using microcrystalline cellulose alone as discussed above.
For claim 7
Hao teaches that hydroxypropyl methylcellulose is widely used polymers in the preparations of solid dispersions (Pg.2, lines 33-34). Hao further teaches use of hot melt extrusion-grade hydroxypropyl methylcellulose polymer as a dispersion carrier in the solid dispersion (Abstract, lines 1-2). Hao also teaches that hot melt extrusion-grade hydroxypropyl methylcellulose polymer exhibits low viscosity and very low hygroscopicity (Pg.8, lines 35-45). Hao further teaches that low viscosity can prevent gelatinization during capsule dissolution and improve bioavailability of poorly soluble drugs (Pg.8, lines 5-8 and 35-40) and low hygroscopicity of polymer improves stability of amorphous drugs and prevent conversion to crystalline forms (Pg.8, lines 25-34 and 43-45).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to use hot melt extrusion-grade hydroxypropyl methylcellulose polymers as taught by Hao in the solid dispersion claimed by US’537 and arrive at the claimed invention. It would have been obvious for a skilled artisan to add the hot melt extrusion-grade hydroxypropyl methylcellulose acetate succinate in the solid dispersion of US’537 because Hao provides solution to potential problems such as poor stability and bioavailability of amorphous drugs.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Hao have demonstrated use of hot melt extrusion-grade hydroxypropyl methylcellulose is known in the art and has advantages of improving bioavailability and long-term stability of amorphous drugs.
For claims 18 and 31
X-ray powder diffraction (XRPD) measurements are known in the art and commonly used for characterizing the crystalline forms of active pharmaceutical ingredients as evidenced by Haitham (Pg.171, 4.2 X-ray power diffraction pattern). The absence of diffraction peaks in the x-ray powder diffractogram at 2-theta angles equal or below 40.0°, when measured at a temperature in the range of from 20 to 30 °C and with Cu-Ka radiation having a wavelength of 1.54056 A or 1.54184 A, is an indication of solid dispersions being in amorphous form as disclosed in the instant specification (Pg.53, lines 2-9). Therefore, the XRPD characterization of the dispersion claimed by US’537, would exhibit same characteristics (absence of diffraction peaks in diffractogram) as claimed in the instant claim 18. Similarly, pharmaceutical composition of compound (1) of US’537 prepared according to Fry as discussed above, would show absence of diffraction peaks in X-ray powder diffractogram as claimed in the instant claim 31.
For claims 19 and 20
Differential scanning calorimetry (DSC) is known in the art and routinely used for characterizing amorphous and crystalline solid dispersions by understanding the phase transitions as evidenced by Ding (Abstract). The single glass transition temperature signal in the differential scanning calorimetry curve obtained from modulated differential scanning calorimetry (MDSC) characterization, indicates the measured solid dispersion is single phase comprising amorphous compound as evidenced by instant specification (Pg.58, lines 14-17). Therefore, solid dispersion of compound (1) claimed in US’537, would be expected to produce single glass transition temperature signal in the range of 90 to 190 ̊C when characterized by MDSC as recited in the instant claims 19 and 20.
For claim 44
Johnson teaches fucoidan (reads as solid drug) in form of capsules can be supplied in a kit comprising sealed container containing capsules (Pg.19, lines 1-6). Johnson also teaches that commonly employed form of packaging of pharmaceuticals can include desiccants (Pg.17, lines 6-9).
It would have been prima facie obvious for a person of ordinary skills in the art before the effective filing date of the claimed invention to provide the pharmaceutical composition of US’537 in a kit comprising container to contain pharmaceutical composition and a desiccant as taught by Johnson and arrive at the claimed invention.
It would have been obvious for a skilled artisan to supply pharmaceutical composition in Kit for administration because Johnson demonstrated supplying pharmaceutical compositions comprising solid dispersions in a kit is routine and known in the art. Furthermore, supply pharmaceutical composition in a kit format including everything needed to administer the composition to the patient provides many benefits. For example, Kitting allows maintaining consistency and quality of medication across all the patients; simplified and easy administration of the medication; streamlining process of preparing/delivering medications, reducing time and resources required for each patients visit; and supplying desiccant in the kit helps maintain integrity of the medication by preventing moisture related degradation and contamination.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/VIJAY D PATEL/ Examiner, Art Unit 1616
/ERIN E HIRT/Primary Examiner, Art Unit 1616