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 .
DETAILED ACTION
Claims 1-11 and 16-19 are pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 3/23/2023 has been considered.
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.
Claim(s) 1-11 and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Menting et al. (US 2019/0241640) and Kirby et al. (US Pub. No.20040202709).
The instantly claimed invention is broadly drawn to a transdermal insulin formulation comprising: (i) insulin; and (ii) a solvent system comprising one or more selected from the group consisting of at least two solvents, at least one solvent modifier, at least one solute modifier, at least one source of cellular activation energy, and at least one skin stabilizer; wherein the solvent system comprises molecular properties substantially similar or approximately +20% to molecular properties of the insulin within the formulation, said molecular properties selected from van der Waals forces and dipole moments, wherein the solvent system further comprises one or more selected from the group consisting of a membrane permeability modifier, an enzyme activator; and a capillary dilator, wherein the solvent system further comprises: (a) a membrane permeability modifier in an amount from 0.01% to about 5% wt/wt of the formulation, (b) an enzyme activator in an amount ranging from about 0.01% wt/wt to about 0.05% wt/wt of the formulation, and (c) a capillary dilator in an amount ranging from about 0.1% wt/wt to about 2% wt/wt of the formulation. The formulation according to claim 1, wherein the insulin is selected from the group consisting of a rapid-acting insulin, a short-acting insulin, an intermediate-acting insulin, a long-acting insulin, and a mixture thereof. The formulation according to claim 1, wherein the at least two solvents are selected from the group consisting of ethanol, propylene carbonate, propylene glycol, and acetone (claim 6), wherein the ethanol is about 37% -54% wt/wt of the formulation, PEG is about 40-51% wt/wt and the acetone is about 0.6-4% wt/wt of the formulation. The formulation of claim 1, wherein the formulation is in liquid dose form, and the formulation comprises 0.2 mL to 1 ml of liquid and comprises insulin from 7 IU /mL to 1700 IU/mL. The formulation of claim1, wherein the solvent comprises one or more selected from the group consisting of lemon oil, vitamin E, phytantriol, dexpanthenol, Lauricidin monolaurate, methylsulfonylmethane (MSM), and forskolin, wherein lemon oil ranges from 0.1% to 0.9% wt/wt of the formulation; the vitamin E is present in an amount ranging from 0.005% wt/wt to 0.1% wt/wt of the formulation; the phytantriol is present in an amount ranging from 0.003% wt/wt to 0.5% wt/wt of the formulation; the dexpanthenol is present in an amount ranging from 0.008% wt/wt to 0.5% wt/wt of the formulation; the monolaurate is present in an amount ranging from 0.09% wt/wt to 0.5% wt/wt of the formulation; the methylsulfonylmethane is present in an amount ranging from 0.1% wt/wt to 1% wt/wt of the formulation; and the forskolin is present in an amount ranging from 0.01% wt/wt to 0.07% wt/wt of the formulation and a process of making the formulation and using the same in a subject in need thereof.
Menting et al. teach a transdermal insulin or insulin analog formulation [0321] in a pharmaceutical composition for transdermal delivery (see paragraph [0329]). The reference teaches a pharmaceutical composition comprising the insulin analog and one or more pharmaceutically acceptable carriers comprising: insulin (para[0037], and one or more pharmaceutically acceptable carriers); and a solvent system comprising one or more selected from the group consisting of at least two solvents, at least one solvent modifier, at least one solute modifier, at least one source of cellular activation energy, and at least one skin stabilizer (para[0037], one or more pharmaceutically acceptable carriers; para[0346], the solvent system; para[0330], the carrier can be as solvent or dispersion medium containing, for example, water, ethanol, glycerol, propylene glycol, and suitable mixtures thereof; para[0329]. Menting et al teach that solutions used can include the following components: antioxidants such as ascorbic acid. Hence, the one or more carriers is the solvent system, and ethanol, glycerol, propylene glycol, and ascorbic acid are applicable solvents for use in the solvent system; because the instant specification para[0016]-[0017], discloses that the solvent system comprises one or more ingredients selected from the group consisting of two or more solvents and at least once source of cellular activation energy, the two or more solvents can be selected from the group consisting of ethanol, propylene glycol, and glycerol; see instant specification para[0020], the at least one source of cellular activation energy can be selected from the group consisting of ascorbic acid); wherein the solvent system comprises molecular properties substantially similar or approximately plus or minus 20% to molecular properties of the insulin within the formulation (para[0037]) are within the aspect of the reference. Menting et al. do not teach that the solvent system comprises lemon oil, vitamin E; phytantriol, dexpanthenol, monolaurate, methylsulfonaylmethane (MSM), and forskolin.
Kirby et al teach a composition for rapid and non-irritating transdermal delivery of pharmaceutically active agent and methods of delivery the same (see the title, Abstract). Kirby et al teach that the transdermal delivery of an active agent includes (i) active agent, (ii) solvent system in which the active agent is soluble, and (iii) a substance capable of in vivo stimulation of cAMP or cGMP [0054]. Kirby et al teach that the substance capable of stimulating cAMP is Forskolin, colforsin or colenol [0055]. They teach that skin stabilizing agent includes (a) non-aqueous non-toxic solvent selected from lower aliphatic mono- and poly-hydroxy compounds; (b) lemon oil, (c) methylsufonylmethane, (d) skin stabilizer such as aliphatic carboxylic acid, vitamin D, aliphatic alcohol having 1-20 carbon atoms and (e ) solute modifier including polyphenolic flavonoid, isoflavones, vitamin D3, vitamin K1 [0059-0071]. They teach that transient modification is manifested by the formation of a complex between the solute (active agent) and the solvent and modifying agents or modifiers for the solvent and the solute [0084]. They teach that the complexes are formed as non-chemical thru solutions of the solute using week association, including van der Waals forces [0084]. They teach that balancing of dipole moments in solvent carriers with active agents may be done for mole-van der Waals forces to within ± 20% (see para [0198]). They teach that suitable amount of solvent modifier is within a range from 0.0001 to about 50% [0097]. They teach that suitable amount of solute modifier about 0.003% to 5% ( see para [0101]). They teach that other modifying agents includes capillary modifier, enzyme activator, source(s) of cellular activation energy [0086]. They teach that preferred mono alcohol includes ethanol, isopropanol; or polyols, such as propylene glycol, ethylene glycol and other solvent can be used for example, acetone, methyl-ethyl ketone [0089]. They teach that in general amount of solvent is in the range of 5-90% [0091]. They teach that solvent modifier such as lemon oil, Vitamin E, Panthenol and methylsulfonylmethane has provided favorable results [0094]. They teach that the amount of activation energy may be from about 0.0001 to about 1% [0109]. They teach that skin stabilizer is from about 0.01% to about 5% (see para [0113]), suitable enzyme activators are in amount of about 0.01% to about 0.05% (see para [0119]), and suitable amount of capillary dilators are in an amount of 0.1 to about 2% [0121]. They teach a method of making a transdermal delivery system comprising the same (Examples 14-17).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use solvents in about 5-50%, solvent modifiers from about 0.0001% to about 50%, solute modifiers from about 0.001 to about 5%, cellular energy activator from about 0.01% to about 1% and skin stabilizer from about 0.1% to a 2% as taught by Kirby et al in a formulation of transdermal delivery composition of insulin or an analog thereof as taught by Menting et al. Additionally, one would have been motivated to do so because Kirby et al teach a transdermal delivery formulation of therapeutic active agent using solvents, solvent modifier, solute modifier, cellular activation energy source and skin stabilizer, wherein the solvent is in the range of 5-90% [0091]. They teach that solvent modifier such as lemon oil, Vitamin E, Panthenol and methylsulfonylmethane has provided favorable results [0094]. They teach that the amount of activation energy may be from about 0.0001 to about 1% [0109]. They teach that skin stabilizer is from about 0.01% to about 5% (see para [0113]), suitable enzyme activators are in amount of about 0.01% to about 0.05% (see para [0119]), and suitable amount of capillary dilators are in an amount of 0.1 to about 2% [0121]. Further, one would have a reasonable expectation of success in using solvents modifiers, solute modifier, source of cellular energy and skin stabilizer because Kirby et al teach making a transdermal delivery system for an active agent. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674