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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/24/2022 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
This action is in response to papers filed 10/13/2025 in which claims 10 was cancelled and claims 1, 9 and 11-13 were amended. All the amendments have been thoroughly reviewed and entered.
Claims 1, 4-6, 9 and 11-13 are under examination.
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn.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.
Maintained-Modified Rejections
Modification Necessitated by Applicant’s Claim Amendments
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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
Claims are 1, 9 and 11-13 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.
The specification states that the oral film of the present invention is “non-mucoadhesive,” meaning “the dosage form is not designed for administration of the active pharmaceutical agent through the oral mucosa…” (p. 5, para. 27 through p. 6, para. 2). The scope may include dosage forms not intended for administration to the oral mucosa. In other words, the instant “non-mucoadhesive” permits complete avoidance of contact with the oral mucosa.
In the relevant art, “non-mucoadhesive” is understood to mean either that the dosage form does not adhere to buccal mucosal surfaces as an intact film or as disintegrated residue (see WO 2011/124570), or that any adherence is only transient — for example, adherence shorter than 60 seconds, preferably shorter than 30 seconds, and in particular shorter than 15 seconds (see WO 2011/138049). Because the specification does not adopt, incorporate, or otherwise clarify either the broader “avoidance of contact” interpretation or the narrower “lack of adhesion” / “brief adhesion” definitions from the prior art, the term “non-mucoadhesive” is indefinite as used in claims 1, 9, and 11–13.
Suggested corrective actions:
- Define “non-mucoadhesive” in the specification to specify whether it means (a) the film avoids contact with the oral mucosa, (b) the film does not adhere to mucosal surfaces (including as residue), or (c) the film adheres only for a defined brief interval (and provide a numerical time limit, if applicable).
- Alternatively, amend the claims to replace “non-mucoadhesive” with a clear limitation reflecting the intended scope, for example “An oral film does not adhere to mucosal surfaces of the buccal cavity as an intact film or as disintegrated film residue.”
For examination purpose, the term “non-mucoadhesive” is interpreted as any adherence to the mucosal surfaces of the oral or buccal cavity is transient and lasts less three minutes.
103 rejection
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.
Claims 1, 4-6, 9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Malhotra et al. (WO 2014/064409 A1) in view of KR101940401B1 (English translation), and further in view of Barnhart et al. (US 9937123).
Malhotra teaches a pharmaceutical composition comprises at least one integrase inhibitor selected from “dolutegravir, elvitegravir, MK-2048, JTK-656, raltegravir” and at least one antiretroviral or anti-HIV agent selected from “zidovudine, didanosine, stavudine, lamivudine, abacavir, adefovir, lobucavir, entecavir, apricitabine, emtricitabine, et…” (abstract; entire; page 8, para. 1 through page 10, para 2). Various combinations are taught as preferred embodiment as following: 1) dolutegravir, tenofovir and emtricitabine/lamivudine combination, 2) elvitegravir, tenofovir and lamivudine combination, 3) elvitegravir, tenofovir and emtricitabine combination, 4) dolutegravir, lamivudine and zidovudine combination, 3) dolutegravir, emtricitabine and lamivudine/zidovudine, 5) dolutegravir, abacavir and lamivudine combination etc.… with one or more pharmaceutically acceptable excipients including carriers, diluents or fillers, binders, lubricants, glidants and disintegrants (page 10, last paragraph through page 12, para. 3; page 14, para. 4-5; Examples), wherein said composition are prepared in various dosage forms including oral or buccal administration, e.g., tablet, granules, pills, beads, etc. … (page 7, para. 6 bridging para. In page 8; page 12, para. 4 through page 15, para. 4). Malhortra teaches that the pharmaceutical composition according the present invention may also be coated i.e., seal coated or film coated, using polymeric materials such as HPMC, hydroxypropyl cellulose, polyvinylpyrrolidone, methylcellulose, carboxymethylcellulose, Hypromellose, acacia, gelatin and polyvinyl alcohol-polyethylene glycol copolymer and polyvinyl alcohol and the like or combination thereof (page 18, para. 2-4). Malhortra further teaches that the composition may be formulated with plasticizers selected from “polysorbates such as sorbitan monolaurate (SPAN 20), sorbitan monopalmitate, sorbitan monostearate, sorbitan monoisostearate, triethyl citrate, citrate phthalate, propylene glycol, glycerin, polyethylene glycol, etc.…” (page 16, para. 7 through page 17, para. 1). Additionally, Malhortra teaches that the pharmaceutical composition may include additional excipients such as bulking agent, flavorants, colourants, etc.… (page 18, para. 5 through page 19, para. 1).
KR101940401B1 teaches taste-masked disintegrating films and preparations methods (entire document; para. [0001]) where the oral disintegration film (ODF) formulation can be formulated with lipids; film-forming polymers selected from “pullulan, gelatin, pectin, low viscosity pectin, hydroxypropylmethylcellulose, low viscosity hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose cellulose, carboxymethylcellulose, polyvinyl alcohol, polyacrylic acid, methyl methacrylate copolymer, carboxyvinyl polymer, polyethylene glycol, alginic acid, low viscosity alginic acid, sodium alginate, carrageenan, modified starch, casein, the water-soluble polymer may be at least one water-soluble polymer selected from the group consisting of water, a water-soluble polymer, a water-soluble polymer, a separation product, jane, levan, elscan, gluten, acacia gum, carrageenan, gum arabic, guar gum, locust bean gum, xanthan gum…”; plasticizer including glycerin fatty acid ester, sucrose fatty acid ester, lecithin, enzyme-treated lecithin, polysorbate, sorbitan fatty acid ester, sorbitol, maltitol, xylitol, glycerin, polyethylene glycol, propylene glycol, starch syrup, glycerin, triacetin, glycerol oleate, triethyl citrate, and a medium chain fatty acid…”; and the additives such as a sweeteners, a flavor, a stabilizer and a pH adjuster (para. [0072]-[0082]). KR101940401B1 teaches the suitable active drug for the oral disintegration film formulation selected from “entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir, indinavir, lopinavir…nevirapine, raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir, or a salt thereof” (para. [0067], [0135]). KR101940401B1 discloses that the claimed ODF formulation is a mount rinse film preparation wherein “the oral disintegration film is a drug-loaded formulation in thin film formulations, and the oral disintegrating film formulation provides several advantages over conventional solid dosage forms, liquids, and oral disintegrating tablets. That is, since the oral disintegrating film preparation can be taken without water, it is very useful not only for the elderly who have difficulties in taking tablets or capsules but also for children, persons with disabilities, patients lying in bed, busy modern people, It is estimated that disintegration is more advanced than any existing formulations. Particularly, when the drug is absorbed into the buccal mucosa, the first pass of the liver can be avoided. Therefore, the buccal disintegration film has an advantage that it can be applied to drugs which are highly metabolized among the drugs absorbed from the digestive tract. Therefore, many efforts have been made to manufacture oral disintegrating film formulations of various techniques for the physical properties of film and patient compliance” (para. [0006]). Also, KR101940401B1 discloses that the oral disintegrating film formulation further improve the taste shielding effect (para. [0070]-[0072]; [0086]-[0089]; [0107]- [0111]).
Barnhart et al. is cited as evidence that, at the time the invention was made, oral dissolvable/disintegrating films with thicknesses of approximately 20 to 300 microns that disintegrate within about three minutes upon contact with saliva were well known. Barnhart teaches a dissolvable or disintegratable film for delivering a pharmaceutical agent where the oral film formulation is prepared with mixture of film form polymers (e.g., hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, poly(ethylene) oxide, etc…), filler, plasticizer (e.g., polyaocohols, sorbitan esters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, triacetin, glycerin, etc...), humectant and other excipients such as flavors, sweeteners, colorants, etc.. (entire document; abstract; col. 2, lines 23-38; col. 3, line 40 through col. 4, line 32; col. 6, lines 27-48; claims 1-19). Barnhart also teaches that the film having thickness in the range of about 20 microns to about 1200 microns, more preferably less than about 250 microns or equal to or less than 200 microns or less than about 175 microns or less than about 75 microns rapidly disintegrate to release the active without causing any undue discomfort to the oral cavity (col. 8, lines 23-36); and that the oral film is disintegrated in the oral cavity within about 20 to 60 seconds after contact with a mucous membrane (col. 2, lines 49-54; col. 42-44; col. 8, lines 57-67; claim 9).
Regarding the instantly claims 1, 4-6, 9 and 11-13, even though Malhotra teaches all the elements of the current invention, i) the reference(s) does/do not expressly name the HIV/anti-retroviral drug or drugs in combination with at least one film forming polymer and at least one plasticizer and optionally with excipients, furthermore the reference does/do not teach the specific characteristic of the formulation having “disintegrates within about three minutes upon contact with saliva, the oral film has thickness of from 20 microns to about 300 microns, and the oral film is non-mucoadhesive” recited in claims 1, 9 11-13.
However, KR101940401B1 teaches the advantage of formulating active drugs such as entecavir, lamivudine, abacavir, atazanavir, zidovudine, cobicistat, stavudine, didanosine, dolutegravir, darunavir, efavirenz, etravirine, elvitegravir, emtricitabine, fosamprenavir, indinavir, lopinavir, nevirapine, raltegravir, ritonavir, rilpivirine, tenofovir, tipranavir, saquinavir, or a salt thereof into an oral disintegrating film (ODF) to mask unpleasant taste. Given this teaching, it would have been obvious to a person of ordinary skill in the art to incorporate one or more known HIV/antiretroviral agents disclosed in KR101940401B1 together with typical ODF components (e.g., film-forming polymer, plasticizer, and other excipients) to produce an ODF formulation that shields the drug’s raw taste. Malhotra’s disclosure would have provided additional motivation and guidance to modify its formulation teachings by combining the known antiretroviral drug(s) with film-forming polymers, plasticizers, and excipients to achieve an oral disintegrating film that masks unpleasant taste.
Consistent with this reasoning, it would have been obvious to have selected various combinations of disclosed ingredients (including the selection of from specific film polymer and plasticizer and/or excipients listed in claim 4-6, respectively, within the prior art disclosure of the Malhortra and the KR101940401B1 ), to arrive at the instantly claimed combination “yielding no more than one would have expected from such an arrangement”. From the prior art teaching alone or in combination, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention since the prior art makes obvious that the film-forming polymer and one or more excipients including plasticizer, fillers/bulking agents, flavoring agents, coloring agents, surfactants and stabilizers have been routinely utilized in making film-coated tablet containing HIV/anti-retroviral drug or HIV/anti-retroviral drugs in combination with integrase inhibitor(s).
It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative step1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Regarding the specific disintegrating characteristic of said oral film formulation recited in claims 1, 4-6, 9 and 11-13, namely “the oral film disintegrates within about three minutes upon contact with saliva, the oral film has thickness of from 20 microns to about 300 microns”, Barnhart teaches that the design of dissolvable/disintegrating films within thicknesses of approximately 20 to 300 microns that disintegrate within about three minutes upon contact with saliva were well known at the time of the invention was made. One having ordinary skill in the art would have understood in light of the cited prior art in combination that delivering of the HIV/retroviral drugs in oral dissolvable/disintergrated film formulation provides advantage of not only convenience to certain patient population (e.g., children, persons with disabilities, patients lying bed, busy modern people but also taste making effects by rapidly disintegrates in oral or buccal mucous membrane by saliva or other aqueous materials on the mucosal surface within about 20 to 60 seconds when the thickness of film is designed within about 20 microns to about 1200 microns, most preferably less than about 75 microns. Thus, one having ordinary skill in the art would have motivated to do so with reasonable expectation of success to arrive at the claimed invention.
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists, thus addressing the specific thickness and the specific disintegrating time. Further, the thickness and time are interpreted broadly considering the Applicant’s use of “about.” In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). MPEP 2144.05 (1).
Regarding the specific characteristic of the oral film formulation recited in claims 1, 4–6, 9, and 11–13—namely, that “the oral film is non-mucoadhesive”—the Examiner interprets “non-mucoadhesive” to mean that any adherence to the mucosal surfaces of the oral or buccal cavity is transient and lasts less than about three minutes. In other words, the film does not adhere to a large extent to the mucosal surface of the oral or buccal cavity since it is disintegrated within about three minutes upon contact with . Although Barnhart describes its oral film as “mucoadhesive,” the reference teaches the use of the same film-forming polymers with other ingredients recited in the instant claims and discloses that the film rapidly disintegrates within about 20 to 60 seconds upon contact with a mucous membrane. Accordingly, the Examiner determines that the prior art teaching meets the claimed non-mucoadhesive limitation.
In light of the forgoing discussion, it is determined that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
Response to Arguments
Applicant's arguments filed 10/13/2025 have been fully considered but they are moot because the applicant’s amendment necessitate a new ground of rejection that does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
With respect to applicant’s argument over Berndl and Bandi, they are found persuasive because the newly added claim limitations recited in claims 11, 9 and 11-13 are not taught. Accordingly, the rejection of claims 1, 4-6 and 10 over Berndl as evidenced by Kibria et al and the rejection of claims 1, 4-6 and 9 over Bandi are withdrawn.
With respect to Applicant’s argument regarding Malhotra, Applicant is correct that Malhotra does not disclose the limitation of an oral film that disintegrates within about three minutes upon contact with saliva or that has a thickness of about 20 microns to about 300 microns, even though Malhotra describes various dosage forms (e.g., tablets, capsules, orally disintegrating tablets, dispersible tablets, granules) (pp. 7–8). However, as discussed in the above § 103 rejection, KR101940401B1 and Barnhart provide the relevant nexus and motivation. KR101940401B1 teaches oral disintegrating films and highlights the advantages of converting active drugs into an ODF format—advantages that include masking unpleasant taste and improving patient convenience for the elderly with swallowing difficulties, children, persons with disabilities, bedridden patients, and other users who prefer or require a non-swallow dosage form. Barnhart further teaches the preparation of ODFs, including film thicknesses in the range of about 20 microns to about 1200 microns (most preferably less than about 75 microns), and that such films rapidly disintegrate to release the active ingredient—about 20 to 60 seconds after contact with a mucous membrane—without causing undue discomfort to the oral cavity. These teachings demonstrate that the claimed disintegration time and thickness were well known at the time the invention was made and would have motivated a person of ordinary skill in the art to modify Malhotra accordingly.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/BRIAN-YONG S KWON/ Supervisory Patent Examiner, Art Unit 1613