DETAILED ACTION
Claims 21-40 are currently pending and under examination.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
The instant application is a continuation of 17/241,793, filed 04/27/2021, which is a continuation of 14/379,613, filed 08/19/2014, which is a national stage entry of PCT/EP2013/053426, filed 02/21/2013, which claims priority to 461/MUM/2012, filed 02/21/2012.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 02/14/2024, 03/27/2024 and 10/15/2024 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 26 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 26 recites the limitation "the particles" in first line. There is insufficient antecedent basis for this limitation in the claim. Instant claim 21, from which it depends, contains limitations directed to first type of particles and second type of particles. It is unclear if “the particle” is referring back to the first type, the second type or both the first and second type of particles.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 21-40 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 2006/0183779 (Applicant provided) in view of US 2003/0195220 and WO 2011/107427 as evidenced by PubChem (PubChem, Dabigatran Etexilate, (accessed 03/21/2016), pgs. 1-25, Applicant provided).
Regarding claim 21-22, the limitation of a composition comprising a) particles that comprise dabigatran etexilate mesylate; and b) particles that comprise at least one pharmaceutically acceptable organic acid is met by the ’779 publication teaching the active substance ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-mthyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionate and the pharmaceutically acceptable salts thereof (abstract) wherein a preferred salt is mesylate [0014], wherein PubChem evidences the structure of the ‘779 publication [0003] is Dabigatran etexilate (page 1, right column, page 3, structure). The ‘779 publication teaches dabigatran etexilate and organic acids provides a significantly improved formulation [0007]. Wherein the core of the pellet containing an organic acid such as tartaric acid, a separating layer followed by a layer containing the active substance ([0008], [0010], Figure 1), thus teaching the acid contained in the core and the drug in a separate layer distinct from the acid.
The limitation of wherein at least one type of particles is coated with a protective coating layer is met by the ‘779 publication teaching the optional outermost layer, which serves to reduce any increased abrasion during packing into capsules ([0013]-[0015]).
The limitation of the second type of particles is coated with a protective coating layer is met by the ‘779 publication teaching the core layer containing an insulating layer and the drug coating layer containing a coating material to reduce abrasion ([0011], [0013], [0015]), thus indicating a coating to be applied over the inner particle layer which contains the acid, wherein the second particle contains the acid.
The limitation of wherein the first type of particles is free from acids is met by the ‘779 publication teaching spatial separation of the organic acid and the active substance, wherein the organic acid and the active agent are taught to be in a particle ([0010], [0011]).
Regarding claim 23-25, the limitation of further comprising at least one pharmaceutically acceptable excipient is met by the ‘779 publication teaching polymer selected from gum Arabic included in the particles [0012]. The ‘779 publication teaches embodiments wherein talc is present (Table 1), wherein the instant specification teaches lubricants include talc [0053]. Binders are taught to be polyvinylpyrrolidone (claim 8), reading on crospovidone.
Regarding claims 26, the limitation of wherein the particles are powder, granules, pellets, beads or mini tablets is met by the ’779 publication teaching pellets [0010].
Regarding claims 27-29, the limitation of the second type of particles has a size range of 100 microns and 900 microns, 400 microns and 700 microns, and the first type of particles has a particle size comprised between 100 microns and 1000 microns is met by the ‘779 publication teaching the size of particles is narrow and the spherical core material has a diameter of 0.4-1.5mm [0012] wherein the size of the pellet is the desired size, the core averaging between 0.6 to 0.8 mm [0017] wherein the final pellet is screened in mesh size of 1.25 mm. As MPEP 2144.05 recites “where 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 optimization”.
Regarding claim 30, the limitation of wherein the protective coating comprises tac, hydroxypropylcellulose or mixtures thereof is met by the ‘779 publication teaching hydroxypropylmethylcellulose outermost layer of film forming agents [0015].
Regarding claim 31, the limitation of wherein the binder is selected form the group including hydroxyethylcellulose is met by the ‘779 publication teaching hydroxyethylcellulose [0019].
Regarding claims 32-33, the limitation of wherein the protective coating layer is seal coated with a pharmecuatially capable film forming agent, specifically hydroxypropylmethyl cellulose is met by the ‘779 publication teaching hydroxypropylmethyl cellulose hard capsules [0021] to be applied over the particles.
Regarding claim 34, the limitation of comprising from 0.01 wt% to 90% of dabigatran etexilate (expressed as dabigatran etexilate mesylate) is met by the '779 publication teaching dabigatran etexilate (abstract, [003]) wherein the active agent is taught to be present at 5-60% [0014].
Regarding claims 35, the limitation of 2-95% of the at least one pharmaceutically acceptable organic acid is met by the ‘779 publication teaching 30-100% of the organic acid in the core [0012].
Regarding claim 36, the limitation of wherein the composition comprises from 50 mg to 200 mg of dabigatran etexilate mesylate is met by the ‘779 publication teaching the mesylate of the compound of form I, present at 50 mg in the capsules (Table 1, [0014], [0030]).
Regarding claim 37, the limitation of wherein the unit dosage form is a capsule is met by the ‘779 publication teaching a capsule [0015].
Regarding claims 38 and 40, the limitation of a capsule composition consisting of a mixture of at least one pharmaceutically acceptable excipient, wherein a) the first type comprising dabigatran etexilate in the form of the free base or in the form of a pharmaceutically acceptable salt or polymer thereof, wherein the first type of particle is free from organic or inorganic acids and a second type comprise at least one pharmaceutically acceptable organic acid, wherein the second type of particles is coated with a protective coating layer and is free form dabigatran etexilate is met by the ‘779 publication teaching structure [0003] is Dabigatran etexilate (page 1, right column, page 3, structure). The ‘779 publication teaches dabigatran etexilate and organic acids provides a significantly improved formulation [0007]. Wherein the core of the pellet containing an organic acid, a separating layer followed by a layer containing the active substance ([0010], Figure 1). The ‘779 publication teaching the optional outermost layer, which serves to reduce any increased abrasion during packing into capsules ([0013]-[0015]). The ‘779 publication teaches embodiments wherein talc is present (Table 1), wherein the instant specification teaches lubricants include talc [0053], the elected excipient. the ‘779 publication teaching the core layer containing an insulating layer and the drug coating layer containing a coating material to reduce abrasion ([0011], [0013], [0015]), thus indicating a coating to be applied over the inner particle layer which contains the acid, wherein the second particle contains the acid. The ‘779 publication teaches the active agent, an organic acid with a protective coating and an excipient.
It is noted that the use of ‘at least one excipient’ allows for additional ingredients in the formulation beyond the listed two particles, and additionally the ‘comprising’ language regarding the first and second particles allows for additional ingredients in the particles.
Regarding claim 39, the limitation of wherein the capsule is a hard capsule comprising gelatine or hydroxypropyl methylcellulose is met by the ‘779 publication teaching hard capsule is hard gelatine and hydroxypropylmethylcellulose [0021].
The ‘779 publication does not specifically teach two distinct types of particles, wherein the first type of particles is free from tartaric acid and the second type of particles is free form dabigatran etexilate mesylate (claim 21).
The ‘220 publication teaches oral administration of medicinal substance wherein an acidic substance is compounded to promote the dissolution of the medicinal substance in digestive tract and thus efficacy can be expressed at the early stage after administration (abstract). The acidic substance can include organic acids such as fumaric acid and tartaric acid [0029]. The process wherein a drug mixture is granulated, a drug mixture containing a medicinal substance and pharmaceutical additive without an acidic substance can be granulated. The resulting granules are then mixed with an acidic substance. The granules of an acidic substance prepared by granulation method above can be used whereby the tablets comprise different granules each containing medicinal substance and acidic substance is separately prepared [0058]. Fumaric acid is sprayed and formed in the granules. Active agent granules and fumaric granules are take form the respective granules are combined with low substituted hydroxypropylcellulose and mixing to form a tablet ([0112], [0113]).
The ‘427 publication teaches oral pharmaceutical composition containing dabigatran etexilate (abstract). The active agent is taught to have strong pH dependent solubility that is greatly increased in the acidic deferment (page 1, last paragraph). The oral pharmaceutical can be in the form of capsule or tablet (page 5, second last paragraph). Fillers are taught to include lactose (page 6, first paragraph). Disintegrants are taught to be cross-linked polyvinylpyrrolidone (crospovidone) (page 6, third paragraph). The oral pharmecuatially composition comprises mixing the active ingredient with the inorganic excipient and optionally further processing steps into tablets or capsules. Preferably micro-encapsulated, adsorbed onto a binder or absorbed into a binder before mixing (page 6, last paragraph). Due to the acidic nature of some of the employed inorganic acidic excipients it may be advantageous to spatially separate these excipients in the pharmaceutical compositions. This can be achieved by micro-encapsulation of the inorganic acid. Alternative the inorganic acidic excipient is present in a core material consisting of or containing an excipient and that the core material is surrounded by an active ingredient containing layer (page 5, fourth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to formulation the oral compristion taught by the ‘779 publication as two distinct particles as the ‘220 publication teaches that it known to formulation compositions comprising distinct active agent and acid containing particles. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to do so as the ‘220 publication teaches the acidic particles are known to improve dissolution. One ordinary skill in the art before the filing date of the claimed invention would be motivated and have an expectation of success in using two separate particles for the active agent and acid in place of the layered structure taught by the ‘779 publication because the ‘427 publication teaches it is known to separately encapsule the acid from the active agent dabigatran etexilate in an oral pharmaceutical compositions, wherein both layering and separately encapsulating acids are taught to be ways of separating the acid from the active ingredient. It would have been obvious to one of ordinary skill in the art at the time the invention was made to combine prior art elements according to known methods to yield a predictable results of separate particles in place of separate layers for the drug and acid formulation and obvious to try based on the ‘220 publication teaching it was known to use two separate particles for acid and active ingredient and the ‘427 publication teaches it is known to separate an acid from dabigatran etexilate through the use of microencapsulating the acid or layering.
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 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,013,729 in view of US 2006/0183779 as evidenced by PubChem (Applicant provided).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant invention and the ‘729 patent are directed to compositions comprising two or more distinct types of particles, the first particle comprise dabigatran etexilate mesylate free of organic acids and a second type of particles comprising an organic acid and free of active ingredient and comprising a protective coating layer.
The instant claims differ in that the acid is specifically tartaric acid.
The ’779 publication teaches the active substance ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-mthyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionate and the pharmaceutically acceptable salts thereof (abstract) wherein a preferred salt is mesylate [0014], wherein PubChem evidences the structure of the ‘779 publication [0003] is Dabigatran etexilate (page 1, right column, page 3, structure). The ‘779 publication teaches dabigatran etexilate and organic acids provides a significantly improved formulation [0007]. Wherein the core of the pellet containing an organic acid such as tartaric acid, a separating layer followed by a layer containing the active substance ([0008], [0010], Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use tartaric acid as taught by the ‘779 publication for the organic acid in the particles as taught by the ‘729 patent because the ‘729 patent teaches the use of organic acids in combination with Dabigatran etexilate and the ‘779 publication teaches the use of a specific organic acid, tartaric acid, to be used in formulations comprising Dabigatran etexilate. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use tartaric acid as the ‘779 publication teaches organic acids such as tartaric acid provide significantly improved formulations with the active agent Dabigatran etexilate. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success of using the acid taught by the ‘779 publication in the formulation taught by the ‘729 patent as the ‘779 publication and the ‘729 patent are both directed to formulations comprising Dabigatran etexilate and an acid, wherein the acid is separated from the active agent.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,752,142 n view of US 2006/0183779 as evidenced by PubChem (Applicant provided).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant invention and the ‘142 patent are directed to compositions comprising two or more distinct types of particles, the first particle comprise dabigatran etexilate mesylate free of organic acids and a second type of particles comprising an organic acid and comprising a protective coating layer.
The instant claims differ in that the acid is specifically tartaric acid.
The ’779 publication teaching the active substance ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-mthyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionate and the pharmaceutically acceptable salts thereof (abstract) wherein a preferred salt is mesylate [0014], wherein PubChem evidences the structure of the ‘779 publication [0003] is Dabigatran etexilate (page 1, right column, page 3, structure). The ‘779 publication teaches dabigatran etexilate and organic acids provides a significantly improved formulation [0007]. Wherein the core of the pellet containing an organic acid such as tartaric acid, a separating layer followed by a layer containing the active substance ([0008], [0010], Figure 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use tartaric acid as taught by the ‘779 publication for the organic acid in the particles as taught by the ‘142 patent because the ‘142 patent teaches the use of organic acids in combination with Dabigatran etexilate and the ‘779 publication teaches the use of a specific organic acid, tartaric acid, to be used in formulations comprising Dabigatran etexilate. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use tartaric acid as the ‘779 publication teaches organic acids such as tartaric acid provide significantly improved formulations. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success of using the acid taught by the ‘779 publication in the formulation taught by the ‘142 patent as the ‘779 publication and the ‘142 patent are both directed to formulations comprising Dabigatran etexilate and an acid, wherein the acid is separated from the active agent.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
/JENNIFER K MICHENER/Group Director, TC 1600