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 .
Specification
The use of the terms “Eudragit” and “Carbopol”, and “Soluplus”, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 12 is objected to because of the following informalities: abbreviations such as “HPMCAS”, “PPVA”, etc. should be written out in the first instance in the claims.
Claims 12, 13, and 18 are objected to because of the following informalities: “Carbomer” and “Poloxamer” need not be capitalized.
Claim 15 is objected to because of the following informalities: “BCS” should be written out in the first instance in the claims, and “classes II or IV” or “class II or class IV”.
Appropriate corrections are 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.
Claims 11-13, and 18 are 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 11 recites “the purity of the beta-lactoglobulin is at least 92% (w/w) of the total amount of protein of the co-amorphous form”. It is ambiguous whether the “at least 92% (w/w)” refers to the beta-lactoglobulin or “the total amount of protein”. Claim 1 recites “the protein is beta-lactoglobulin”, which implies the purity level relates to the beta-lactoglobulin. In that case the beta-lactoglobulin should not comprise any other protein. However claim 11 recites “the total amount of protein of the co-amorphous form” which implies proteins other than beta-lactoglobulin may be present. (If so claim 11 would require a rejection under 35 U.S.C. 112(d).) Consequently it is unclear (1) whether the phrase at issue relates to the purity of beta-lactoglobulin or to all the protein in the co-amorphous form, and (2) if it relates to the purity of beta-lactoglobulin, whether it could contain other proteins or non-protein impurities. For the purposes of examination now the claim phrase is construed as beta-lactoglobulin is the protein in the co-amorphous form.
Claim 12 contains the trademark/trade names “Carbopol®”, “Eudragit®” and “Soluplus®”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe certain water-soluble and water-swellable synthetic polymeric materials (Carbopol®), synthetic methacrylate polymers (Eudragit®), and a water-soluble graft copolymer (Soluplus®), and, accordingly, the identification/description is indefinite.
Also in claims 12, the terms “[p]oloxamer type polymers”, “polymethacrylate-based copolymers”, “Eudragit type polymers”, and “cellulose derivative”, render the claim indefinite because the claim includes elements not actually disclosed (those encompassed by "type", “-based”, or “derivative”), thereby rendering the scope of the claim unascertainable. See MPEP § 2173.05(d). The terms "type", “-based”, or “derivative” broaden that which they modify, however the extent of what is encompassed in "type", “-based”, or “derivative” is not recited or disclosed. A derivative indicates any chemical modification, the extent of which is not recited or disclosed. Consequently each term renders the scope of the claim unclear. Claims 13 and 18 also recite the term "[p]oloxamer type".
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-12, 14, 16, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hajihashemi (Hajihashemi, Z., et al. Interactions among lactose, β-lactoglobulin and starch in co-lyophilized mixtures as determined by Fourier Transform Infrared Spectroscopy. J Food Sci Technol 51, 3376–3382 (2014)) as evidenced by Nasirpour (Nasirpour, A, et al., Modeling of Lactose Crystallization and Color Changes in Model Infant Foods, Journal of Dairy Science Volume 89, Issue 7, July 2006, Pages 2365-2373).
Hajihashemi studied co-lyophilized lactose, β-lactoglobulin (BLG), and gelatinized starch (title; abstract; p.3377 Model infant formulation preparation). The formulation remained amorphous and stable after 3 months of storage at various relative humidity levels (Fig.3b and accompanying text). Lyophilization involves solvent or water evaporation (see Nasirpour p.2365-66).
Claim 18 is rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Vergauwen (US 2019/0083629).
Vergauwen teaches a “pharmaceutical formulation comprising a protein based excipient in combination with an active pharmaceutical ingredient ( API ) wherein said formulation is substantially amorphous and form a substantially homogenous mixture” (abstract; see entire document including paras.0002, 0006, 0013-22, 0031-24). Vergauwen further teaches, “[b]y combining different excipients an improved (synergistic) effect may be observed , which would further improve the solubility , dissolution rate and / or bioavailability exceeding that of the excipients when used separately”, specifically “[c]ommon[sic] non-protein excipients are designer polymers …and examples may include , but are not limited to , Polyvinyl pyrrolidone (PVP)…, Soluplus®, and the like” (para.0210; see paras. 0209, 0211, 0264-65, 0341-46).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 and 11-17 are rejected under 35 U.S.C. 103 as being unpatentable over Mishra (US 2019/0307886) in view of Vergauwen (US 2019/0083629).
Mishra teaches “pharmaceutical, cosmetic or veterinary compositions comprising… as well as to methods for preparing and using” a “co-amorphous form of a substance and a protein”(abstract; see title; paras.0001-06, 0091-92; claims 1, 26-49). Mishra teaches co-amorphous forms comprising various drugs (Table 1), and specifically teaches beta-lactoglobulin as a suitable protein (e.g., paras.0006, 0019, 0022-23, 0030-54, 0124, 0134, 0203, 0217; Fig.4b; claim 1). Mishra also discusses prior art use of polymers such as those in instant claim 12 to form co-amorphous forms of insoluble or poorly soluble drugs (paras.0140-44, 0219). Specifically regarding polyvinyl pyrrolidone (PVP), Mishra states, PVP “is the most commonly used excipient for making solid dispersions , which is the main competing technology for amorphization in terms of optimizing solubility and / or stability of drug substances with poor solubility and / or stability properties” (para.0140, 0144).
Mishra does not specifically teach using both beta-lactoglobulin and PVP.
Vergauwen teaches a “pharmaceutical formulation comprising a protein based excipient in combination with an active pharmaceutical ingredient ( API ) wherein said formulation is substantially amorphous and form a substantially homogenous mixture” (abstract; see entire document including paras.0002, 0006, 0013-22, 0031-24). Vergauwen further teaches, “[b]y combining different excipients an improved (synergistic) effect may be observed , which would further improve the solubility , dissolution rate and / or bioavailability exceeding that of the excipients when used separately”, specifically “[c]ommon[sic] non-protein excipients are designer polymers …and examples may include , but are not limited to , Polyvinyl pyrrolidone (PVP)…, Soluplus®, and the like” (para.0210; see paras. 0209, 0211, 0264-65, 0341-46).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to combine the teachings of Mishra and Vergauwen and use both beta-lactoglobulin and PVP or another polymer that Vergauwen teaches to from amorphous solid dispersions or the co-amorphous form as recited in the instant claim(s). The skilled person would have been motivated to do so because both references are drawn to improving solubility of poorly soluble substances by amorphization of the substance with proteins, and Vergauwen teaches “[b]y combining different excipients an improved (synergistic) effect may be observed , which would further improve the solubility , dissolution rate and / or bioavailability exceeding that of the excipients when used separately”, including specifically “designer polymers” such as those in instant claim 12 (para.0210).
Claim(s) 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Vergauwen (US 2019/0083629) in view of Song (Song, Y., et al., Acid−Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study, Mol. Pharmaceutics 2016, 13, 483−492).
Regarding claim 19 Vergauwen does not expressly teach using polystyrene sulfonate.
Song is drawn to “potential drug-excipient interactions of polystyrene sulfonic acid (PSSA) and two weakly basic anticancer drugs, lapatinib (LB) and gefitinib (GB), in amorphous solid dispersions” (abstract). “PSSA was found to significantly improve the dissolution of LB and GB and effectively inhibit the crystallization of LB and GB under accelerated storage conditions due to the beneficial strong intermolecular acid−base interaction between the sulfonic acid groups and basic nitrogen centers” (abstract; see Figs. 2, 10, 11 and accompanying text).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to combine the teachings of Vergauwen and Song and use a protein in combination with polystyrene sulfonate in forming an amorphous solid dispersion or a “co-amorphous” form with a drug as recited in the instant claim(s). The skilled person would have been motivated to do so because Vergauwen teaches using both and does not limit the polymer excipient to those it lists as examples (para.0210), and Song teaches that PSSA’s strongly acidic group stabilizes weakly basic groups in active pharmaceutical ingredients which stabilizes the amorphous form.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 11-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12564554 in view of Vergauwen (US 2019/0083629).
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both claims sets are drawn to a co-amorphous form of an active pharmaceutical ingredient or a nutraceutical, and beta-lactoglobulin. A difference(s) between the two claim sets is that the '554 patent claims recite the purity of the beta-lactoglobulin in the independent claim whereas here dependent claim 11 does so. The present claims further recite a water-soluble polymer in the co-amorphous form. However Vergauwen teaches a “pharmaceutical formulation comprising a protein based excipient in combination with an active pharmaceutical ingredient ( API ) wherein said formulation is substantially amorphous and form a substantially homogenous mixture” (abstract; see entire document including paras.0002, 0006, 0013-22, 0031-24). The skilled person would have been motivated to include a water soluble polymer in the co-amorphous form because Vergauwen further teaches, “[b]y combining different excipients an improved (synergistic) effect may be observed , which would further improve the solubility , dissolution rate and / or bioavailability exceeding that of the excipients when used separately”, specifically “[c]ommon[sic] non-protein excipients are designer polymers …and examples may include , but are not limited to , Polyvinyl pyrrolidone (PVP)…, Soluplus®, and the like” (para.0210; see paras. 0209, 0211, 0264-65, 0341-46).
Claims 1 and 11-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 11-19 of copending Application No. 18/564552 in view of Vergauwen (US 2019/0083629).
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both claims sets are drawn to a co-amorphous form of a nutraceutical or a dietary supplement and beta-lactoglobulin. The difference(s) between the two claim sets is that the present claims further recite a water-soluble polymer in the co-amorphous form. However Vergauwen teaches a “pharmaceutical formulation comprising a protein based excipient in combination with an active pharmaceutical ingredient ( API ) wherein said formulation is substantially amorphous and form a substantially homogenous mixture” (abstract; see entire document including paras.0002, 0006, 0013-22, 0031-24). The skilled person would have been motivated to include a water soluble polymer in the co-amorphous form because Vergauwen further teaches, “[b]y combining different excipients an improved (synergistic) effect may be observed , which would further improve the solubility , dissolution rate and / or bioavailability exceeding that of the excipients when used separately”, specifically “[c]ommon[sic] non-protein excipients are designer polymers …and examples may include , but are not limited to , Polyvinyl pyrrolidone (PVP)…, Soluplus®, and the like” (para.0210; see paras. 0209, 0211, 0264-65, 0341-46).
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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