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 .
Applicants’ arguments, filed 04/13/2026, have been fully considered. Rejections and/or objections not reiterated from previous office action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Election/Restrictions
Applicant’s election of the species readable on claims 1-4, 6-8, 11, 13, and 19 in the reply filed on 04/13/2026 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)).
Claims 9-10, 12, 14-18 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/13/2026 for the reasons set forth above.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 1-4, 6-8, 11, 13, and 19 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 term “poorly” in claim 1 is a relative term which renders the claim indefinite. The term “poorly” 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. It is not clear what is meant by this term such that the artisan would reasonably appreciate the metes and bound of what is encompassed by it. It is not clear at how far the absorbability of a drug can deviate and still meet the requirement of the claim.
Claims 1 recites “molar ratio of the anion and the cation is 1:1 to 5:1”. Claims 6 and 8 recite “molar ratio of the anion and the cation is 5:1” and “molar ratio of lactic acid and trometamol is 5:1.” This is indefinite because it is unclear which number in the ratio is assigned to anion (lactic acid). For the purposes of examination the ratio will be interpreted as anion to cation (i.e., anion:cation (lactic acid:trometamol) at a ratio of 1:1 to 5:1).
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
1) Claims 1, 4, 7, 11, 13 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Kawai et al. (JP2008184402A, publication date 08/14/2008, citing machine English translation) in view of Hanma et al. (US 2010/0029704 A1, publication date 02/04/2010), as evidenced by Adawiyah et al. (Med. Chem. Commun., 2016, v. 7, p. 1881-1897).
Kawai discloses “[t]he solubilization of compounds hardly soluble in organic solvents is achieved by using a Bronsted-type ionic liquid as a solvent or a dissolution auxiliary” [abstract]. “The ‘ionic liquid’ referred to in the present invention refers to a salt that is liquid at room temperature (25 ° C.) among salts obtained by equimolar reaction of a Bronsted carboxylic acid compound and a basic compound. As the carboxylic acid compound, levulinic acid, glyoxylic acid, glycolic acid, lactic acid, malic acid, citric acid, benzoic acid, salicylic acid, and glycine are used” [paragraph spanning pages 7-8]. “On the other hand, examples of the basic compound include diethanolamine, triethanolamine, triisopropanolamine, glycine, 2-amino-2-methyl-1-propanol, and 2-amino-2-hydroxymethyl-1,3-propanediol. Preferably, organic ethanol compounds such as diethanolamine, triethanolamine, triisopropanolamine, 2-amino-2-methyl-1-propanol, 2-amino-2-hydroxymethyl-1,3-propanediol are used” [p. 8, 1st full para.]. Furthermore, Kawai discloses “the ionic liquid of the present invention can dissolve medicinal components that are hardly soluble in organic solvents” [p. 7, para. 3]. Kawai discloses the composition has low irritation to the skin [abstract].
Kawai’s disclosure of medicinal components that are hardly soluble in organic solvents at paragraph 3 of page 7 suffices as a poorly absorbable drug, as evidenced by Adawiyah which disclosed diminishing of bioavailability is aggravated when the drug molecules are insoluble or sparingly soluble in pharmaceutically accepted organic solvents (see Adawiyah at [p. 1882, col. 2, first half of para. 1]).
Kawai does not disclose a hydroxypropyl cellulose.
Hanma discloses an ionic liquid comprising a carboxylic acid and an organic amine compound [abstract] which may be administered to the skin as a gel [0054]. According to Hanma, hydroxypropryl cellulose is suitable for use as a gel base for the ionic liquid composition [0058].
Generally, it is prima facie obvious to select a known material based on its suitability for its intended use. See MPEP 2144.07.
In the present case, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have selected the hydroxypropyl cellulose gel base of Hanma for the formulations of Kawai because Hanma discloses hydroxypropyl cellulose is a suitable gel base for ionic liquid compositions for delivering an active agent.
Additionally, given the disclosure of each component individually, it would have been prima facie obvious for a person having ordinary skill in the art at, before the effective filling date of the claimed invention, to have selected and combined known components for their established functions with predictable results by following the teachings of Kawai. MPEP 2143 and 2144.06(I).
Finally, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). In the present case, the instantly claimed molar ratio of 1:1 to 1:5 (anion to cation) overlaps with the 1:1 ratio of the prior art and so a prima facie case of obviousness exists.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated an oral composition comprising an ionic liquid, a poorly absorbable drug and hydroxypropyl cellulose, wherein the ionic liquid comprises lactic acid and trometamol at the instantly claimed molar ratios. There is nothing in the prior art composition that would have precluded oral administration. As such, the prior art composition would have been capable of fulfilling the claimed intended use of oral administration.
2) Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Kawai et al. (JP2008184402A, publication date 08/14/2008, citing machine English translation) in view of Hanma et al. (US 2010/0029704 A1, publication date 02/04/2010), as evidenced by Adawiyah et al. (Med. Chem. Commun., 2016, v. 7, p. 1881-1897) as applied to claims 1, 4, 7, 11, 13 and 19 above, and further in view of Christiansen et al. (US 8,710,181 B2, publication date 04/29/2014).
Kawai and Hanma, which are taught above, differ from the instant claims insofar as they do not disclose a molecular weight of the drug and a GLP-1 agonist. However, Kawai does disclose that “[t]he medicinal component is not particularly limited, and examples thereof include peptides” [penultimate paragraph of page 8].
Christiansen discloses “tris-(hydroxymethyl) aminomethane [CAS 77-86-1; trometamol], and similar biological buffering substances have shown to be superior in stabilizing peptides, polypeptides and proteins, including Glucagon-Like Peptides (GLPs, analogs and derivatives thereof) in solution” (i.e., water-soluble) [col. 2, lines 38-43]. According to Christiansen “’GLP-1 peptide', as used herein, is intended to designate GLP-1 (7-37)” [col. 3, lines 66-67].
GLP-1 (7-37) has a molecular weight of 3355.7 g/mol, as evidenced by Pubchem.
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have combined the GLP-1 peptides, namely GLP-1 (7-37), of Christiansen with the drug delivery composition taught by Kawai and Hanma. One would have been motivated to select the GLP-1 (7-37) of Christiansen because Christiansen discloses it as an example peptide for the superior stabilizing effect of trometamol, i.e., a components of the composition taught by Kawai and Hanma. One would have had an expectation of success because Kawai desires peptides as the medicinal component of the ionic liquid. Additionally, in combining these elements one would have expected nothing more than predictable results because, when combined by known methods, each prior art element would have performed the same function as it had separately. See MPEP 2143, Exemplary Rationale A.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated the composition comprising an ionic liquid taught by Kawai and Hanma and discussed above, to comprise a water soluble GLP-1 agonist with a molecular weight within the instantly claimed range.
3) Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kawai et al. (JP2008184402A, publication date 08/14/2008, citing machine English translation) in view of Hanma et al. (US 2010/0029704 A1, publication date 02/04/2010), as evidenced by Adawiyah et al. (Med. Chem. Commun., 2016, v. 7, p. 1881-1897) as applied to claims 1, 4, 7, 11, 13 and 19 above, and further in view of Tanner et al. (Advanced Materials, 2019, v. 31, 1901103).
Kawai and Hanma, which are taught above, differ from the instant claims insofar as they do not teach lactic acid to trometamol molar ratio of 5:1.
Tanner relates to design principles of ionic liquids for transdermal drug delivery [title] and discloses that “Ionic liquids (ILs) and deep eutectic solvents have shown great promise in drug delivery applications” [abstract]. Tanner also discloses “the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE [choline and geranic acid ionic liquid], which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery” [abstract].
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have formulated a composition comprising the anion (lactic acid) and cation (trometamol) at a molar ratio within the instantly claimed range through routine optimization. It has been held that it is not inventive to discover the optimum workable ranges by routine experimentation where, as is here, the general conditions of the claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). One of ordinary skill in the art would have been motivated to optimize the molar ratio because Tanner teaches that ion stoichiometry effects skin penetration of drugs. One would have had an expectation of success because Tanner exemplifies ionic liquids having ions that are not present at equimolar ratios.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention, to have taught by Kawai to comprise lactic acid and trometamol at a molar ratio as instantly claimed.
Response to Arguments
1. On pages 4-5 of their Remarks filed 11/20/2026, Applicant argues that the instant claims are not obvious over Towfly Bioscience et al. (CN 102363633 A, hereinafter "Towfly") because Towfly does not disclose oral administration.
This argument is moot in view of the new rejections set forth above.
2. On page of their Remarks filed 11/20/2026, Applicant argues the instantly claimed composition possesses unexpectedly superior absorption of a poorly absorbable drug that is orally administered. Furthermore, applicant asserts the instantly claimed molar ratio is critical in yielding a result that is superior to and unexpected.
This argument is not persuasive. Overcoming a rejection based on unexpected results requires the combination of three different elements: (i) the results must fairly compare with the prior art, (ii) the results must truly be unexpected and (iii) the claims must be commensurate in scope. MPEP §716.02. The burden rests with Applicant to establish results are unexpected and significant. MPEP §716.02(b). Applicant's showing of allegedly unexpected results does not satisfy any of these requirements.
(i) In the present case the results have not been compared to the closes prior art. The closes prior art appears to be Kawai at Example 3 on page 9. Example 3 comprises lactic acid and organic amines of Table 5 (translation below) in equimolar amounts [p. 9, Example 3]. Therefore the closest prior art is a composition comprising lactic acid and diethanolamine in equimolar amounts.
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(ii) The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (MPEP 716.02(b)). In the present case the allegedly unexpected result of superior absorption of a poorly absorbable drug that is orally administered do not appear to be, in fact, unexpected over the prior art. For example, at the penultimate paragraph of page 7, Kawai discloses “the solvent or dissolution aid comprising the ionic liquid of the present invention often exhibits lipophilicity despite being a salt. Therefore, various drugs can be dissolved. Therefore, when considering a percutaneously absorbable preparation, the skin barrier is the presence of hydrophilic and hydrophobic layers, but the ionic liquid of the present invention is easily osmotically dissolved in the skin barrier due to its properties” [p. 7, second half of penultimate paragraph]. That is to say, the ionic liquid, and the active agent dissolved therein, of Kawai easily penetrates the skin because the liquid has ionic and lipophilic characteristics. Therefore, a skilled artisan would have reasonably expected the ionic liquids of Kawai to enhance drug absorption when orally administered by means of the same mechanism.
Furthermore, Adawiyah discloses “[t]he pharmaceutical industries are experiencing a series of challenges, including the administration of solid crystalline forms of many drugs, because of their low water solubility and polymorphic conversion, which can diminish their bioavailability. Such problems are further aggravated when the drug molecules are insoluble or sparingly soluble in pharmaceutically accepted organic solvents. Fortunately, the tunable properties of ILs allow their possible utilization as engineered pharmaceutical solvents or in the formation of new drug molecules with particular attributes that are generally restricted in conventional solvents” [p. 1882, col. 2]. Therefore, a skilled artisan would have known that ionic liquids improve bioavailability by enhancing the solubility of drugs. As a result, a skilled artisan would have reasonably expected that ionic liquids, which enhance solubility, would improve the absorption of drugs when administered orally.
With respect to the claimed range, to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). (MPEP 716.02(d)). In the present case applicant has only disclosed results for compositions comprising lactic acid and trometamol at a 2:1 and 5:1 molar ratio (lactic acid to trometamol). Applicant has not provided results for compositions comprising lactic acid and trometamol outside the claimed molar ratios.
Accordingly, the Examiner is not able to determine if the claimed ranges are truly critical to the function of the invention.
(iii) The "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support" (see MPEP 716.02(d) quoting In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)). In the present case the claims are not commensurate in scope with the objective evidence because the independent claim does not recite a molecular weight for the claimed drug. According to Example 6 and Figure 6, molecular weight affects the absorption of dextran, i.e., a poorly absorbable drug according to paragraph 47. Specifically, the absorption of the inventive composition and comparative composition overlap at high molecular weights of dextran (see Figure 6 of the instant disclosure). Therefore, it does not appear that the improved absorption would be present over all molecular weights of drugs.
Technological Background
The prior art made of record is considered pertinent to applicant's disclosure.
National Center for Biotechnology Information. PubChem Compound Summary for CID 16133830, Glucagon-like peptide 1 (7-37). https://pubchem.ncbi.nlm.nih.gov/compound/Glucagon-like-peptide-1-_7-37. Accessed May 7, 2026, which is pertinent for teaching to molecular weight of GLP-1(7-37).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to COLMAN WELLES whose telephone number is (571)272-3843. The examiner can normally be reached Monday - Friday, 8:30am - 5:00pm ET.
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/C.T.W./ Examiner, Art Unit 1612
/WALTER E WEBB/ Primary Examiner, Art Unit 1612
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