-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 .
Applicant’s response dated February 16, 2026 is acknowledged.
Priority
This application is a 371 of PCT/CN2021/126995 filed on 12/28/2021.
Claim Status
Claims 27-36 are pending and examined. Claims 1-26 were canceled. Claims 32-36 were newly added and read on the elected invention of Group III.
Election/Restriction
Applicant’s election of Group III (Claims 27-31), drawn to a sublingual tablet in the reply filed on February 16, 2026, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, non-elected claims were canceled and no claims are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being withdrawn to a non-elected invention, and non-elected species of the invention, there being no allowable generic or linking claims.
Response to the restriction requirement of December 30, 2025 was timely filed.
Claims 27-36 are examined on the merits.
Information Disclosure Statement
Foreign document 1 cited in IDS dated 04/25/2024 was not considered because applicant did not provide a copy of the document.
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 32, 33, and 35 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 32 contains the trademark/trade name Tween. 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 name is used to identify/describe a disintegrating agent and, accordingly, the identification/description is indefinite.
The term “low-substituted hydroxypropyl cellulose” in claim 32 is a relative term which renders the claim indefinite. The term “low” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 33 recites “microcrystalline cellulose-mannitol” and “microcrystalline cellulose-micronized silica gel”. These phrases render the claim indefinite because it is unknown what structure is implied by the hyphen connecting microcrystalline cellulose to mannitol, and the hyphen connecting microcrystalline cellulose to micronized silica gel.
Claim 35 contains the trademark/trade name carbomer. 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 name is used to identify/describe a binder and, accordingly, the identification/description is indefinite.
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.
Claims 27, 28, and 31-36 are rejected under 35 U.S.C. 103 as being unpatentable over Bolen (US 2018/0193270 A1 Published July 12, 2018 – of record in IDS dated 04/25/2024) and Schwarz (US 2018/0311146 A1 Published November 1, 2018).
The claims are drawn to a sublingual tablet, wherein the tablet includes drug-loaded milk exosomes.
The teachings of Bolen are related to exosomes as drug delivery vehicles and compositions comprising a therapeutic agent encapsulated within such exosomes (Abstract). In some embodiments, exosome is a milk-derived exosome (paragraph 0064). In one aspect, a
therapeutic-loaded milk exosome is provided, wherein the therapeutic is a biologic therapeutic agent and the therapeutic is not naturally-occurring in a milk exosome (paragraph 0076). In some embodiments, the therapeutic-loaded exosomes or pharmaceutical compositions thereof are administered by sublingual route (paragraphs 0074 and 0650). Table 1 teaches exemplary therapeutic agents which include insulin and insulin detemir (paragraph 0601). Pharmaceutically acceptable compositions may be orally administered in any orally acceptable dosage form including, but not limited to tablets (paragraph 0653).
Bolen does not specifically teach tablets as a sublingual dosage from.
The teachings of Schwarz are related to self-emulsifying compositions for transmucosal delivery of biologically active peptides and proteins (Abstract). The compositions are intraoral solid pharmaceutical compositions for sublingual administration containing a biologically active peptide such as insulin or insulin analogs, glucagon-like peptide and analogs such as GLP-1, exenatide, or liraglutide (paragraph 0040). The composition for delivery of insulin and other peptides may be in the form of a compressed tablet. Additionally, the tablet can comprise non-ionic surfactants, fillers, such as pharmaceutical grade polyols or sugars (e.g., sucrose, sorbitol, mannitol, erythritol), binders (Polyvinylpyrrolidone, cellulose esters, polyethylene glycols), disintegrants (cross-carmellose, cross-povidone), preservatives (e.g., parabens, sorbic acid, benzoic acid and pharmaceutically acceptable salts thereof), lubricants, glidants, flavors,
antioxidants, etc. These components are incorporated into tablet matrix, prepared by granulation, blending and compression (paragraph 0052). Tablet matrix granulate, containing insulin and
other excipients and suitable for compression, could be prepared by wet granulation, compaction, trituration or dry blending. Tablets were compressed into round, oval or other required shape tablets using appropriate tablet press (paragraph 0053).
The teachings of Bolen and Schwarz are related to peptide drugs such as insulin intended for sublingual administration and it would have been obvious to have combined their teachings because they are in the same field of endeavor.
Regarding claim 27, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formulated a pharmaceutical composition comprising drug-loaded milk exosomes wherein the composition is intended for sublingual administration, with a reasonable expectation of success because Bolen teaches drug-loaded milk exosomes as drug carriers wherein the exosomes are formulated into a pharmaceutical composition intended for sublingual administration. It would have been obvious to have selected as peptide drug such as insulin as the active agent because Bolen teaches that peptide drugs such as insulin are suitable for delivery via exosomes. While Bolen teaches formulating oral dosage forms into a tablet, Bolen does not specifically teach a sublingual dosage form in the form of a tablet. It would have been obvious to have formulated the sublingual dosage form in the form of a sublingual tablet with a reasonable expectation of success because Schwarz teaches that peptide drugs such as insulin may be administered sublingually via a sublingual tablet. The selection of a known material based on its suitability for its intended purpose supports obviousness and combining prior art elements according to known methods to obtain predictable results supports obviousness.
Regarding claim 28, it would have been obvious to have formulated the sublingual tablet with liraglutide as the active agent, with a reasonable expectation of success because Schwarz teaches that liraglutide is a suitable peptide drug that may be administered sublingually via a sublingual tablet.
Regarding claim 31, it would have been obvious to have formulated the tablet with insulin detemir, with a reasonable expectation of success because Bolen teaches that insulin detemir is a suitable drug for sublingual administration.
Regarding claims 32 and 33, it would have been obvious to have formulated the tablet with starch and mannitol because Schawrz teaches tablets in Table 4 that contain starch and mannitol (paragraph 0173).
Regarding claim 34, it would have been obvious to have formulated the tablet with sucralose because Schwarz teaches tablets in Tables 2 and 3 which contain sucralose (paragraph 0173).
Regarding claim 35, it would have been obvious to have formulated the tablet with polyvinylpyrrolidone because Schwarz teaches tablets in Tables 2, 3, and 4 which contain polyvinylpyrrolidone (paragraphs 0173).
Regarding claim 36, it would have been obvious to have formulated the tablet with hydrogenated PEG-40 castor oil because Schwarz teaches tablets in Tables 2, 3, and 4 which contain hydrogenated PEG-40 castor oil (paragraph 0173). Castor oil is a vegetable oil. Alternatively, it would have been obvious to have formed the tablet with PEG 3350 because Schwarz teaches tablets in Tables 2, 3, and 4 which contain PEG 3350. Polyethylene glycol 4000 is obvious over PEG 3350 because their molecular weights are close enough in number that the skilled artisan would have expected them to have the same properties. PEG 4000 contains about 90 repeating units whereas PEG 3350 contains about 76 repeating units.
Alternatively, it would have been obvious to have formulated the tablet with a lubricant because Schwarz teaches that the tablet contains lubricants (paragraph 0052). It would have been obvious to have selected magnesium stearate as the lubricant with a reasonable expectation of success because Bolen teaches magnesium stearate as a lubricant suitable for making an oral tablet (paragraph 0653).
Claim 29 are rejected under 35 U.S.C. 103 as being unpatentable over Bolen and Schwarz as applied to claims 27, 28, and 31-36 above, and further in view of Lee (2016/0375018 A1 Published December 29, 2016).
The claim encompasses the sublingual tablet of claim 28 and further define the excipients.
The teachings of Bolen and Schwarz are relied upon as summarized above. They do not teach purified water in the tablet.
The teachings of Lee are related to solid drug formulations (Abstract). The dosage form comprises diluents, disintegration agents, binding agents, wetting agents or lubricants. In one embodiment, the diluents are lactose hydrate and microcrystalline cellulose; the disintegration agents are cross-linked sodium carboxymethyl cellulose and sodium carboxymethyl starch; the binding agents are hydroxypropyl cellulose and polyvinylpyrrolidone; and the lubricants are magnesium stearate and stearic acid. See Table 2 for concentrations (paragraph 0025). The solid drug formulations include dosage forms such as sublingual tablets. In one embodiment, the tablet is formed by granulation and after the granulation step is accomplished, the wet clot is sieved through a mesh with sieves to remove the agglomerates and increase the drying efficiency. The fluidized bed dryer or the drying oven may be used for drying until the water content is 0.1-2% wt. After drying achieves standard, the dried granules are sieved through a mesh with 30 sieves to remove the agglomerates to forma first mixture. Next, the additional excipients such as microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose and magnesium stearate are sieved through a mesh with 30 sieves to remove the agglomerates, and subsequently added into the aforementioned completely dried granules (first mixture) and mix evenly to form a second mixture. The mixed granules undergo powdered molding in an appropriate tablet mold and tablet machine to form a solid dosage form. In one embodiment, the weight percentage of polysorbate in the final solid dosage form (comprising added component after granulation) is 0.1-0.6% wt., for example, is 0.3% wt.; and the weight percentage of sodium lauryl sulfate is less than or equal to 1.0% wt. Furthermore, the pure water and N,N-dimethyl acetamide used in the present method are removed during preparation of the tablet and tile standard residual amount is established to ensure the product quality (paragraph 0026). According to Example 1, a tablet contains pure water, cross-linked sodium carboxymethyl cellulose, microcrystalline cellulose, and magnesium stearate, among others (paragraph 0028).
The teachings of Lee and Bolen modified with Schwarz are related to sublingual tablets and it would have been obvious to have combined them because they are in the same field of endeavor. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed Bolen’s sublingual tablet comprising cross-linked sodium carboxymethyl cellulose, mannitol, purified water, and lubricant, with a reasonable expectation of success because Schwarz teaches forming a tablet intended for sublingual administration, wherein the tablet comprises disintegrants such as cross-carmellose, sugars such as mannitol, and lubricants.
It would have been obvious to have selected magnesium stearate as the lubricant because it was known from Lee that magnesium stearate is a suitable lubricant in tablets intended for sublingual administration.
It would have been obvious to have formed the tablet by wet granulation using water because Schwarz teaches forming the tablet by wet granulation and it was known from Lee that tablets intended for sublingual administration may be formed by wet granulation using pure water (paragraph 0029) where the final tablet contains pure water (paragraph 0028). Therefore, it would have been obvious to have formed the tablet Bolen by wet granulation process using water, where the final tablet comprises water.
Bolen’s tablet made in view of Schwarz and Lee meets all of the claimed limitations because it contains cross-linked sodium carboxymethyl cellulose, mannitol, purified water, and magnesium stearate.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Bolen and Schwarz as applied to claims 27, 28, and 31-36 above, and further in view of Lee (2016/0375018 A1 Published December 29, 2016) and Soler Ranzani (US 2012/0283262 A1 Published November 8, 2012).
The claim encompasses the sublingual tablet of claim 28 and further define the excipients.
The teachings of Bolen and Schwarz are relied upon as summarized above. They do not teach sodium carboxymethyl cellulose and microcrystalline cellulose in the tablet.
The teachings of Lee are relied upon as summarized above.
The teachings of Lee and Bolen modified with Schwarz are related to sublingual tablets and it would have been obvious to have combined them because they are in the same field of endeavor. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed Bolen’s sublingual tablet comprising a diluent, polyvinyl pyrrolidone, mannitol, and lubricant, with a reasonable expectation of success because Schwarz teaches forming a tablet intended for sublingual administration, wherein the tablet comprises diluents (paragraph 0113), binders such as polyvinylpyrrolidone, sugars such as mannitol, and lubricants.
It would have been obvious to have selected microcrystalline cellulose as the diluent because it was known from Lee that microcrystalline cellulose is a suitable diluent in tablets intended for sublingual administration.
It would have been obvious to have selected magnesium stearate as the lubricant because it was known from Lee that magnesium stearate is a suitable lubricant in tablets intended for sublingual administration.
Bolen modified in view of Schwarz and Lee does not teach sodium carboxymethyl cellulose.
The teachings of Soler Ranzani are related to pharmaceutical compositions (Abstract), including sublingual tablets (paragraph 0088). The compositions include excipients such as a binder selected from water, carmellose sodium, and polyvinyl pyrrolidone (paragraph 0069).
It would have been obvious to have further modified Bolen’s tablet by replacing polyvinylpyrrolidone with sodium carboxymethyl cellulose (carmellose sodium), with a reasonable expectation of success because it was known from Soler Ranzani that carmellose sodium and polyvinylpyrrolidone are binders suitable for making sublingual tablets and replacing one equivalent with another to obtain predictable results supports obviousness.
Bolen’s tablet made in view of Schwarz, Lee, and Soler Ranzani meets all of the claimed limitations because it contains microcrystalline cellulose, sodium carboxymethyl cellulose, mannitol, and magnesium stearate.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617