DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 30-50 are pending in this application.
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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit under 35 USC 120 as a continuation of US application No. 18/587,915 filed on 26 Feb. 2024 (US patent No. 12,453,700 B2) and claims benefit under 35 USC 119(e) to US provisional application No. 63/447,312 filed on 21 Feb. 2023.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 1 Apr. 2026 as being considered by the examiner.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: in claim 1, the recitation of “average particle size of less than or equal to 35 nm” is not supported in the specification.
Claim Objections
Claims 30, 32, and 50 are objected to because of the following informalities: in claim 30, “MK-9 (menaquinone-9)” and “MKH2-9 (menaquinol-9)” should be “menaquinone-9 (MK-9)” and “menaquinol-9 (MKH2-9)” and in claim 50, “the composition of any one of the composition of” should be “the composition of” and in claim 32 the recitation of “caprylate/caprate” should be “caprylate or caprate”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 34 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. In claim 34, the recitation of “genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one))” is indefinite because it is not clear if what is in parentheses is an example or required limitation.
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.
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.
Claim(s) 30-49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Devane et al. (US 2011/0064803 A1; published 17 Mar. 2011; see attached 892), in view of Brand et al. (US 2018/0221283 A1; published 9 Aug. 2018; see attached 892) and Drouet et al. (US 2020/0079718 A1; published 12 Mar. 2020; see attached 892).
Devane et al. teach nanoparticulate and controlled release compositions comprising vitamin K2 (see title). Devane et al. teach nanoparticulate compositions having enhance bioavailability allow smaller dose to give the same in vivo blood levels ([0012]). The redispersed vitamin K2 particles of the invention (redispersed in aqueous biorelevant or other suitable media) having effective average particle size of less than about 50 nm ([0084], [0124]). Devane et al. teach an aqueous dispersion of vitamin K2 (menatetrenone) combined with one or more surface stabilizers at concentrations shown in table 8 was milled in a 10 mL chamber of a nanomill. All compositions were milled for 60 in at a speed of 2500 ([0230], table 8). The particle size of the milled vitamin K2 particles were measured in Milli Q water. Vitamin K2 particle size was measured initially and then again following 60 sec sonication ([0232], table 10). Representative examples of surface stabilizers include polyoxyethylene castor oil derivatives ([0095]). Devane et al. teach polysorbate 80 or tween 80 (see table 8). Devane et al. teach medium chain fatty acids as an enhance capable of enhancing absorption and/or bioavailability of an active ingredient by promoting net transport across the GIT in an animal ([0179]). The invention relates to a nanoparticulate vitamin K2 composition for the treatment of osteoporosis ([0012], [0033], [0046]).
Devane et al. do not disclose a composition comprising nanoparticles of MK-9 or MKH2-9, water, and polyoxyl castor oil wherein the nanoparticles have an average particle size of less than or equal to 35 nm, optionally wherein the nanoparticles are prepared using a bead mill homogenizer optionally further comprising an emulsifier such as polysorbate 80, and optionally further comprising bioavailability enhancer such as MC fatty acids optionally wherein the nanosuspension is in water optionally further comprising a pharmaceutically acceptable excipient wherein the composition is effective for the treatment of a condition associated with vitamin K. Devane et al. do not further teach a method for treatment of a disease in a mammal or patient selected from neurodegenerative diseases, osteoporosism, calciphylaxis, such as distal or central calciphylaxis or calciphylaxis related dermal lesion, diabetes, COPD, chronic kidney disease, cancer such as leukemia optionally wherein the method includes administering at least 0.01 mg of the composition per day.
Drouet et al. teach menaquinol compositions and methods of treatment (see title). Drouet et al. teach MK-9 as a long chain menaquinone ([0003], [0011], [0027], [0029]). Vitamin K2 is preferentially used in the brain, vasculature, breasts, and kidneys (see [0004]). Drouet et al. teach reducing vascular calcification (see [0010]). The effects if long chain menaquinones on normal blood coagulation is greater and longer lasting than vitamin K1 and MK-4. MK-7 has been shown to have a long half-life in serum when compared to MK-4 ([0011]). Drouet et al. teach kolliphor EL (polyoxyl castor oil) ([0109]). Drouet et al. teach treating calciphylaxis in a mammal. In one embodiment the mammal has distal or central calciphylaxis. Drouet et al. teach treating diabetes, chronic kidney disease or end stage renal disease ([0084]). Drouet et al. teach treating neurodegenerative diseases, atherosclerosis, etc ([0081]). Drouet et al. teach treating COPD and calciphylaxis-related dermal lesions (see [0085]). Drouet et al. teach treating cancer, leukemia and inflammatory disease ([0082]). Drouet et al. teach a method of treating, preventing, slowing the progression or, arresting and/or reversing tissue calcification in a pre-diabetic mammal with diabetes, CKD, or a combination thereof ([0092]).
Brand et al. teach a nanosuspension containing particles and extract of natural materials (see title). Brand et al. teach a nanosuspension of the preparation of a medicament and/or nutritional supplement (see abstract). Band et al. teach that the nanoparticles are believed to be taken up faster and to a higher amount compared to other preparations ([0022]). Brand et al. teach an aqueous nanosuspension. The water used as a solvent may be of any kind ([0075]-[0076]). Brand et al. teach vitamins ([0080]). Brand et al. teach a wet ball (bead) mill ([0092]). Brand et al. teach preferred stabilizers include polyethylene (polyoxyl) castor oil ([0083]). If the particle size is not further reduced during milling step or if the particle size is increased during milling step it is preferable to add a stabilizer ([0082]). Brand et al. teach polysorbate-80 ([0083]). Brand et al. teach that when steric stabilizers are used as stabilizers, the steric stabilizer is adsorbed or attached onto the surface of the nanoparticle and provides a large and dense steric barrier which overcomes attractive Van der Waals forces and hence the steric stabilizer reduces aggregation, agglomeration or even particle fusion. It is preferable to add a steric stabilizer in an amount from 0.5 to 2% during milling step ([0086], [0116]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compositions of Devane et al. (a composition comprising; nanoparticles of vitamin K2 and water and a surfactant stabilizer obtained by milling using a NanoMill (bead mill) and optionally comprising at least one emulsifier) so that the surfactant stabilizer is a polyoxyl castor oil as taught by Devane et al., Drouet et al., and Brand et al. because that surfactant stabilizer would have been expected to advantageously provide a steric stabilizer that reduces aggregation, agglomeration or even particle fusion whereby enabling an optimal particle size during milling. It would have been further obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. so that the vitamin K2 is an MK-9 or MKH2-9 as taught by Drouet et al. because those forms of vitamin K2 would have been expected to advantageously enable greater and longer lasting effects. The average particle size of the nanoparticles in the suspension is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. MPEP 2144.05.II. A person of ordinary skill in the art would have arrived at an average particles size that is less than 125 nm by using polyoxyl castor oil as a steric stabilizer during milling in order to arrive at an optimal take up speed and amount and provide optimal stability.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. so that the composition the composition further comprises at least one emulsifier and/or pharmaceutically acceptable excipient such as polysorbate 80 or co-solvent as taught by Devane et al. and Brand et al. because that emulsifier would have been expected to provide improved stability. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. so that the compositions further comprise at least one bioavailability enhancer selected from medium chain fatty acids as taught by Devane et al. and Brand et al. because it would have been expected to advantageously enable enhanced absorption and bioavailability of the active ingredient. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. by further treating a vitamin K deficiency or osteoporosis in a subject with a vitamin K deficiency or osteoporosis by administering to a mammal or patient a therapeutical effective amount of the obvious vitamin K2 nanoparticle composition because it would have been expected to advantageously enable effective treatment of the disease using a low dose of vitamin K2 with enhance bioavailability. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. by further treating a subject who is optimally prediabetic for a disease selected from a neurodegenerative disease such as AD, calciphylaxis such as distal calciphylaxis, diabetes, CKD, COPD, calciphylaxis related dermal lesion, calcification with diabetes or CKD, cancer or leukemia in a subject in need thereof, the method comprising administering a therapeutically effective amount optionally at least 0.1 mg of the obvious vitamin K2 nanoparticle composition as taught by Devane et al., Drouet et al., and Brand et al. because it would have been expected to advantageously enable treatment of those diseases using a low dose of therapeutically effective vitamin K2 with enhanced bioavailability.
Claim(s) 30-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Devane et al. (US 2011/0064803 A1; published 17 Mar. 2011; see attached 892), in view of Brand et al. (US 2018/0221283 A1; published 9 Aug. 2018; see attached 892) and Drouet et al. (US 2020/0079718 A1; published 12 Mar. 2020; see attached 892), in further view of Chou et al. (US 2015/0320702 A1; published 12 Nov. 2015; see attached 892).
Devane et al. teach as discussed above.
Devane et al. do not further teach a method for treating, preventing, slowing the progression of, arresting and/or reversing AD in a mammal or a subject in need thereof.
Brand et al. teach as discussed above.
Drouet et al. teach as discussed above.
Chou et al. teach compositions and methods for treating neurological disease using vitamin K2 derivatives (see title, abstract). Chou et al. teach VK compositions that are neuroprotective ([0009]). Chou et al. teach treating AD ([0011],[0016],[0174], [0296]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Devane et al. by further treating, preventing, slowing the progression of, arresting and/or reversing AD in a mammal or a subject in need thereof by administering to the mammal or subject at least 0.01 mg of the obvious composition of claim 30 as further taught by Chou et al. because it would have been expected to advantageously enable therapeutically effective treatment of AD using an advantageous vitamin K2 nanosuspension.
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 30-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,453,700 B2.
Claims 1-22 of U.S. Patent No. 12,453,700 B2 claim a composition comprising nanoparticles of MK-9 and MKH2-9, water, and polyoxyl castor oil wherein the nanoparticles have an average particle size of less than 125 nm or less than 35 nm wherein the nanoparticles are prepared using a homogenizer such as a bead mill homogenizer wherein the composition further comprises polysorbate 80 and further comprises at least one bioavailability enhancer such as medium chain fatty acids wherein the nanosuspension is in water and wherein the composition further comprises a pharmaceutically acceptable excipient and claim a method for the treatment of a disease selected from neurodegenerative diseases and claim a method of treating and prevention of osteoporosis and claim a method of treating, preventing, slowing, arresting, and or reversing calciphylaxis wherein the mammal has distal calciphylaxis optionally diabetes, CKD, COPD, calciphylaxis related dermal lesion and claim a method of treating or reversing tissue calcification in a pre-diabetic mammal or a mammal with diabetes or CKD wherein the method comprises administering to the mammal at least 0.01 mg of the composition of claim 1 in a pharmaceutical composition wherein the mammal has CKD, cancer optionally melanoma, leukemia, or inflammatory disease and claim a method of treating a mammal with vitamin K deficiency and claim a method for treating, preventing, slowing, arresting or reversing AD.
Claims 1-22 of U.S. Patent No. 12,453,700 B2 do not claim the claimed compositions and methods wherein the nanoparticles have an average nanoparticle size of less than or equal to 35 nm.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-22 of U.S. Patent No. 12,453,700 B2 so that the nanoparticles have a nanoparticles size of less than or equal to 35 nm as taught by claims 1-22 of U.S. Patent No. 12,453,700 B2 because those nanoparticle sizes would have been expected to provide equivalent nanoparticle sizes suitable for use as a vitamin K2 medicament.
Claims 30-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 12,383,514 B2, in view of Brand et al. (US 2018/0221283 A1; published 9 Aug. 2018; see attached 892) and Drouet et al. (US 2020/0079718 A1; published 12 Mar. 2020; see attached 892).
Claims 1-24 of U.S. Patent No. 12,383,514 B2 claim a composition comprising nanoparticles of MK-7 or MKH2-7, water and polyoxyl castor oil wherein the nanoparticles have an average particle size of less than 125 nm wherein nanoparticles are prepared using a homogenizer such as bead mill homogenizer wherein the composition further comprises a medium chain fatty acid and wherein the composition is a nanosuspension in water and wherein the composition further comprises a pharmaceutically acceptable excipient and wherein the nanoparticles are less than 75 nm and claim a method for treating a disease in a mammal such as a neurodegenerative disease and claim a method for treating a disease such as vitamin K deficiency, osteoporosis and claim a method for treating, preventing, slowing, and/or reversing calciphylaxis in a mammal optionally distal or central calciphylaxis optionally wherein the mammal has diabetes, CKD, COPD or a calciphylaxis related dermal lesion and claim a method of treating, preventing, slowing, or reversing tissue calcification in a prediabetic mammal optionally wherein the mammal has CKD and wherein the proliferating disease is selected from cancer optionally melanoma, leukemia or an inflammatory disease and claim a method for treating, preventing, slowing, arresting or reversing AD in a mammal.
Claims 1-24 of U.S. Patent No. 12,383,514 B2 do not claim MK-9 or MKH2-9 or claim an average nanoparticle size of less than or equal to 35 nm or claim a composition further comprising polysorbate-80.
Drouet et al. teach as discussed above.
Brand et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-24 of U.S. Patent No. 12,383,514 B2 so that the nanoparticles are of MK-9 or MKH2-9 as taught by Drouet et al. and Brand et al. because MK-9 and MKH2-9 would have been expected to provide equivalent vitamin K2 derivatives expected to have a long serum half-life. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-24 of U.S. Patent No. 12,383,514 B2 so that the composition further comprises polysorbate 80 as taught by Brand et al. because the polysorbate 80 would have been expected to provide enhanced stability. The average particle size is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill in the art would have arrived at particle size of less than or equal to 35 nm in order arrive at an optimal uptake speed and amount and provide optimal stability.
Claims 30-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-54 of copending Application No. 19/272,770, in view of Brand et al. (US 2018/0221283 A1; published 9 Aug. 2018; see attached 892) and Drouet et al. (US 2020/0079718 A1; published 12 Mar. 2020; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 30-54 of copending Application No. 19/272,770 claim a composition comprising nanoparticles of MK-8 or MKH2-8, water and polyoxyl castor oil wherein the nanoparticles have an average particle size of less than 125 nm wherein nanoparticles are prepared using a homogenizer such as bead mill homogenizer wherein the composition further comprises a medium chain fatty acid and wherein the composition is a nanosuspension in water and wherein the composition further comprises a pharmaceutically acceptable excipient and wherein the nanoparticles are less than 75 nm and claim a method for treating a disease in a mammal such as a neurodegenerative disease and claim a method for treating a disease such as vitamin K deficiency, osteoporosis and claim a method for treating, preventing, slowing, and/or reversing calciphylaxis in a mammal optionally distal or central calciphylaxis optionally wherein the mammal has diabetes, CKD, COPD or a calciphylaxis related dermal lesion and claim a method of treating, preventing, slowing, or reversing tissue calcification in a prediabetic mammal optionally wherein the mammal has CKD and wherein the proliferating disease is selected from cancer optionally melanoma, leukemia or an inflammatory disease and claim a method for treating, preventing, slowing, arresting or reversing AD in a mammal.
Claims 30-54 of copending Application No. 19/272,770 do not claim MK-9 or MKH2-9 or claim an average nanoparticle size of less than or equal to 35 nm or claim a composition further comprising polysorbate-80.
Drouet et al. teach as discussed above.
Brand et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 30-54 of copending Application No. 19/272,770 so that the nanoparticles are of MK-9 or MKH2-9 as taught by Drouet et al. and Brand et al. because MK-9 and MKH2-9 would have been expected to provide equivalent vitamin K2 derivatives expected to have a long serum half-life. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 30-54 of copending Application No. 19/272,770 so that the composition further comprises polysorbate 80 as taught by Brand et al. because the polysorbate 80 would have been expected to provide enhanced stability. The average particle size is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill in the art would have arrived at particle size of less than or equal to 35 nm in order arrive at an optimal uptake speed and amount and provide optimal stability.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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