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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/6/26 has been entered.
Claim Status
Claims 5 and 8 have been cancelled.
Claims 1-4, 6, 7 and 9-19 are pending.
Claims 1-4, 6, 7 and 9-13 are allowed.
Withdrawn rejections
Applicant's amendments and arguments filed 12/18/25 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: the claimed continuous process for melt-coating an active pharmaceutical ingredient (API) appears to be free of the art. There does not appear to be any teaching or suggestion in the art to select a processing temperature that is below the melting point of the surfactant and no lower than 10 °C below the melting point of the surfactant that results in 30% or more of the outer surface of the API particles where the API particles comprise at least 90 wt% based on the weight of the melt-coated API particles. Accordingly, claims 1-4, 6, 7 and 9-13 are free of the art.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 14-19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Chowrai et al. (US20160128944) and Passerini et al. (European Journal of Pharmaceutical Sciences 15 (2002) 71–78).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
PNG
media_image1.png
348
870
media_image1.png
Greyscale
Regarding the product-by-process limitation, please note that the Examiner has taken into the consideration the structural elements provided by the continuous process in producing the drug product. However, in product-by-process claims, “once a product appearing to be substantially identical is found and a 35 U.S.C. 102/103 rejection [is] made, the burden shifts to the applicant to show an unobvious difference.” See MPEP 2113 Product-by-Process Claims [R-08.2017] I. PRODUCT-BY-PROCESS CLAIMS ARE NOT LIMITED TO THE MANIPULATIONS OF THE RECITED STEPS, ONLY THE STRUCTURE IMPLIED BY THE STEPS “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical drug formulation research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical drug formulation techniques including hot-melt extrusion, pharmaceutical active ingredients, pharmaceutically acceptable excipients and chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 14-18, Chowrai et al. teach coated particles and compositions (Title; Abstract; claims 94-101 and 110) comprising from about 0.01-50% w/w of the particles (Claim 111) and further comprising one or more excipients from about 5-99.99% w/w including Poloxamer 407 (Claims 112-113; [0120]) and poloxamer 188 [0108-0109] as well as wetting agents (surfactants) polysorbate and cetylpyridinium chloride [0119] and glyceryl monostearate [0215], where embodiments with Poloxamer 188 and 407 are taught where the surfactants can be used alone or in combination in the melt process (Examples 21-22 and 38; [0563-0565, 0596, 0599, 0606-0608], for example). Example 38 teaches 2% poloxamer 407 [0607] and Example 44 teaches 2% adapalene suspension in 2% poloxamer solution (Example 44; [0631-0632; Table 35), which is at least 1 wt%. Also note other coating weight percentages, for example Table 25 teaches coatings of 2 wt% and 5 wt% (Pages 62-63) as well as 7, 10 and 18 wt% in Table 26 (Page 63), which is at least 1 wt%. The active agent can be present from about 1-99% w/w (Claim 101) and be ibuprofen or acetaminophen or indomethacin or corticosteroids or vitamins (Claim 100) and thus be present in at least 90 wt%. The surface of the API appears more than 30% covered as determined by SEM images (Figure 15; [0036]). Especially when Chowrai et al. teach that multiple layers can be present [0041] and that the core can be fully coated [0045], which is reasonably interpreted to mean 100% covered and is more than 30%. Thus, the particles of the surfactant adhere to the API particle surfaces of the melt-coated API particles.
Regarding claim 19, Chowrai et al. teach the composition in the form of powder (Claim 114) and for oral administration in the form of tablets, suspensions or capsules [0171].
Regarding claims 14-19, Passerini et al. teach that melt granulated ibuprofen and poloxamer 188 “showed an increase in the dissolution rate of granules compared to pure drug and physical mixture.” (Abstract; page 71, left column 2.2.2. Preparation of physical mixture and solid dispersion; Page 75, Figure 4; Conclusion). Passerini et al. report: “The dissolution rate of pure ibuprofen is very low: in fact the percentage of drug dissolved in 10 min is 22.3% and the formation of physical mixture does not improve this value. On the contrary, both the melt granules and the solid dispersion show a great increase in the dissolution of drug compared to pure ibuprofen: 58.0 and 74.5% of drug are dissolved in the first 10 min in melt granules and solid dispersion, respectively.” (Page 74, 3.3. In vitro dissolution studies). Passerini et al. also teach that poloxamer 188 has a low melting point (52 °C) widely used as a wetting and solubilizing agent (Page 71, right column last paragraph) and suggests testing poloxamer 188 to improve the dissolution rate of different poorly water soluble drugs (Page 78, top right column). In Figure 2 (Page 74), SEM images of ibuprofen, solid dispersion and melt granules are shown where it appears the entire ibuprofen crystal is covered in the melt granule. The Examiner notes that Figure 2b represents a solid dispersion made by fusion of melted poloxamer 188, the drug and lactose (Page 72, 2.2.2. Preparation of physical mixture and solid dispersion). Both Figure 2b and 2c show rough exterior with rough bumps similar to what Applicant shows in Figure 9d and 9e.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Chowrai et al. is that Chowrai et al. do not expressly teach the surfactant has a melting point of at least 10 degrees centigrade lower than the API melting point with the functional limitations claimed including wherein the melt-coated API particles have enhanced dissolution as compared to a physical mix of the API and the surfactant of instant claims 14-18. This deficiency in Chowrai et al. is cured by the teachings of Passerini et al.
1. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select a surfactant that has a melting point of at least 10 degrees centigrade lower than the API melting point and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because of the following rationale. It is merely judicious selection of known surfactants picked from a list and known active agents picked from a list as suggested by Chowrai et al. Furthermore, the art of Passerini et al. teaches melt granulated ibuprofen and poloxamer 188 showed an increase in the dissolution rate of granules compared to pure drug and physical mixture. Consequently, in view of the combined references, there is a predictable expectation of enhancing the dissolution of melt-coated API particles such as ibuprofen, with a surfactant, such as poloxamer 188, as compared to a physical mix of the API and the surfactant. It is simply a matter of selecting the appropriate API and surfactant combination taught by Chowrai et al. MPEP 2144.07 states: “The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v.Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)”. "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." (Sinclair & Carroll Co., Inc. v. Interchemical Corp., 325 U.S. at 335, 65 USPQ at 301). Consequently, the ordinary artisan would have a reasonable expectation of success in selecting the same surfactants and the same APIs in the same amounts taught by Applicant where the surfactant that has a melting point of at least 10 degrees centigrade lower than the API melting point to produce a coated API drug product/oral composition dosage form. Further regarding the functional limitations claimed, see MPEP 2112.01(I) WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. In view of the combined references, the functional limitations of claims 14-18 are obvious in the absence of evidence to the contrary. Where the claimed and prior art products are identical or substantially identical the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on "inherency" under 35 U.S.C. § 102, on "prima facie obviousness" under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO' s inability to manufacture products or to obtain and compare prior art products. In re Best, 562 F.2d 1252, 1255 (CCPA 1977). See MPEP 2112(V).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s arguments filed 12/18/25 have been carefully considered but are not persuasive.
On page 7 of remarks, Applicant cites a part of the specification that teaches that subjecting a blend of at least one API with at least one surfactant to simultaneous shear and heat causes localized melting of the particles in direct contact with API particles. That promotes the adhesion of the particles to the surface of the API particle. In response, the Examiner understands that the combined shear and heat are enough to melt the particles in direct contact with the API particles. Thus, a melt-coated API is produced. From the Examiner’s perspective the final product is a melt-coated API that is not structurally different from the melt-coated API of the prior art. While the method to produce the API appears novel, the ultimate product appears the same.
On page 8 of remarks, Applicant asserts that the particles of the surfactant adhere to the API particle surface. In response, the Examiner notes that the particles are melted by the heat and continuous shear forces onto the surface of the API to produce a melt-coated product. As evidenced by Nandi et al. ( Pharmaceutics 2021, 13, 624: 31 pages), in twin screw granulation the temperature in the barrel can easily reach 70 °C (Page 6, 3.1. Temperature)(Please note MPEP 2131.01 III: Also note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date.) Thus, low temperature melting surfactants such as poloxamer 188 (MP about 52 °C) or poloxamer 407 (MP 53-57 °C) will melt due to the combined heat and friction of shearing in twin screw granulation to melt-coat the API. The Examiner still does not find any structural distinction in the final products. Especially in view of Passerini et al. Figure 2 SEM images of the solid dispersion and melt granule.
On page 8 of remarks, Applicant discusses Figure 15 of Chawrai. Applicant’s arguments have been considered but the Examiner is relying on Figure 15 for this teaching: The surface of the API appears more than 30% covered as determined by SEM images (Figure 15; [0036]).
On page 8 of remarks, Applicant asserts that it can be observed from Applicant's own data that melt-coated Ibuprofen particles with 10% poloxamer407 exhibit substantially enhanced dissolution as compared to uncoated Ibuprofen particles and as compared to an untreated mixture. However, Passerini et al. have also demonstrated the same results with ibuprofen coated with poloxamer 188. Both poloxamers have similar melting points. Therefore, this is not an unexpected or surprising result. Applicant’s arguments are not persuasive.
On page 9 of remarks, Applicant asserts that Chawrai is directed to personal care compositions and that the ordinary artisan would not consult a reference directed to topical cosmetic formulations let alone a reference directed to toxic non-ingestible materials. Respectfully, the Examiner does not agree because while some embodiments of Chawrai are directed to personal care embodiments, such as claim 114, the scope of the composition of claim 110 includes embodiments directed to pharmaceutical compositions for administration to humans including oral administration in the form of solutions, suspensions, tablets, pills, capsules, sustained-release formulations, oral rinses or powders as known in the art [0171] as well as parenteral administration [0168-0170] and cites the Handbook of Pharmaceutical Excipients [0120]. Thus, Chawrai is directed to ingestible therapeutic compositions that would not pose significant safety concerns but rather offer therapeutic relief. Applicant’s arguments have been carefully considered but are not persuasive.
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 1-4, 6, 7 and 9-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-19 and 22-23 of copending Application No. 18694042. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending also teaches a process for manufacturing an oral dosage form by introducing an API selected from favipiravir, ibuprofen, carbamazepine, fenofibrate, indomethacin, imatinib, flufenamic acid, erlotinib hydrochloride, vitamin D, estradiol and a surfactant comprising poloxamer, polyoxyethylene stearate, cetylpyridinium chloride, polysorbate, and glyceryl monostearate into a twin-screw blender processer to form a melt-coated API granulates (claims 1 and 6-9), which would be at least partially coated with surfactant, with a processing temperature approximately equal to the surfactant (Claims 2-3) in a continuous process (Claim 16) to make a tablet, capsule or powder (Claim 14) with excipients (Claims 10-12) under closed loop control (Claim 17). The processing temperature of the twin screw processor is from approximately the melting point of the surfactant to 3 °C below the melting point of the surfactant (Claims 1-3), which is within the claimed range. The amount of API is at least 90% by weight (Claim 1). The copending also teaches a dosage form prepared by the process (Claims 18 and 19), including granulates where the dosage form has faster dissolution than a comparative dosage form that differs only by having been made from a physical mix of the API and surfactant, as determined by the time required to release 80% of the darunavir from the dosage form (Claims 22 and 23).
While the copending does not expressly teach that the surfactant coats 30% or more of the outer surface of the API particles, as determined by SEM images, since the same materials and same methods are employed then such naturally occurs when performing the method of the copending application.
While the copending does not expressly teach that the API has an equilibrium solubility of less than 50 mg/ml in de-ionized water at 25 degrees centigrade, such would be implicit in the same APIs claimed.
While the copending does not expressly teach wherein the surfactant has a melting point of at least 10 degrees centigrade lower than the API melting point, such would be implicit in the same surfactants and same APIs claimed.
Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the copending subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments:
Applicant requested that the rejection be held in abeyance. At this time the rejection is maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERNST V ARNOLD/Primary Examiner, Art Unit 1613