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
The present application is a National Stage entry of International application PCT/US2023/020173 filed 04/27/2023, which claims the benefit of Provisional US application 63335306 filed 04/27/2022.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 10/28/2024, in the matter of Application N° 18/861,068. Said documents have been entered on the record. The Examiner further acknowledges the following:
Claims 133-152 are pending.
Claims 133-152 are presented for examination and rejected as set forth below.
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.
Claims 133-135 and 137-150 are rejected under 35 U.S.C. 103 as being unpatentable over Ray (US20220047590A1; published 02/17/2022 compared to the provisional filing date 04/27/2022), and in further view of Pavliv (US20110257240A1), Kerdpol (Polymers, 2019), and Loftsson (Internation Journal of Pharmaceutics, 2001).
Applicant’s claims are directed to a composition comprising an HMG-CoA inhibitor and cyclodextrin dispersed in a hydrogel, wherein the hydrogel comprises water and a polypeptide, including a method of use, dressing, and making.
Ray teaches a topical statin composition for treatment of a wound (abstract) including a method of treatment (Ray – claim 12) and making (Ray - claim 1). Ray further teaches additives including solubilizers, stabilizers, etc. [0036, 0043, 0046] to promote statin dissolution [0040].
Regarding claim 133, 137-138, and 141-142: Ray teaches an aqueous gel formulation (reads on “hydrogel” and “water” of instant claim 133) [0034-0042, 0154], including gelatin ingredient (reads on “polypeptide” of instant claim 133, because gelatin contains polypeptides, whereby Applicant names gelatin as a polypeptide by example in the Specification at pg 14-15) [0042, 0046], comprising one or more statins (reads on “HMG-CoA inhibitor” of instant claim 133), selected from atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin or simvastatin (Ray – claim 2), that includes dissolved, suspended, or dispersed solute formulations (reads on “dispersed” of instant claim 133) [0034].
Regarding claim 139-140: Ray teaches an additional active agent [0041] including antibiotics, etc. [0096-0099].
Regarding claim 147-150 : Ray teaches a method of treating variety of wounds by applying the composition, that include damage, including mechanical damage, infected wounds (from bacteria, virus, fungus), etc. (Ray – claim 1 and 12; [0003]).
In summary, Ray teaches gel compositions comprising statins and a method of treating wounds. Ray further teaches solubilizers and stabilizers [0043], such that the active drug would be mixed, dispersed, suspended solubilized and/or dissolved [0144]. However, Ray does not teach the cyclodextrin and concentration (instant claims 133-135, 143-144) or the explicit teaching of uncomplexed statin in the presence of cyclodextrin (instant claims 145-146).
Pavliv teaches stabilized statin formulations (abstract, [0048]), whereby cyclodextrin such as hydroxy-propyl-beta-cyclodextrin (HPbCD), would complex the statin (Pavliv – claims 4 and 5) in order to improve solubility and/or stabilize the formulation (abstract, [0018, 0039]). Pavliv teaches a 1-25 mg/mL (i.e., for example, lovastatin MW 404 g/mol calculates to 2.5 - 61.8 mM, overlapping the instant range of claim 143) solubilized statin concentration (i.e., meaning there is at least the same molar equivalent of solubilized complexing agent, i.e., this reads on a 1:1 ratio of inhibitor to cyclodextrin). In further support of the drug to cyclodextrin amount, Pavliv teaches embodiments containing 0.1 to 90 wt% statin [0055], and/or more than 13.5 wt% complexing agent (i.e., equals to [0041] (i.e., reading on the instant ratios and embodiments of claims 144-146). Pavliv’s compounds are intended for topical administration among other formats, including transdermal patches [0048].
Kerdpol further teaches the structural aspects of a-, b-, g-cyclodextrins and 2-HPbCD (i.e., reads on n+m = 6, 7, or 8) (pg 2), and demonstrates the obviousness of C2 substitution (as in 2-HPbCD of instant claim 135) and/or C6 substitution of cyclodextrins (reads on R1 and/or R2 substitution of instant claim 134), with a ring size of 7 glucopyranose subunits (i.e., reads on n+m = 7) (Figure 2). Kerdpol summarizes by teaching that specific CD substitution (including single-sided substitution) leads to conical and/or flipped confirmations, that would be suitable for encapsulation of low-water soluble compounds (pg 12), to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation (abstract).
Loftsson teaches uncomplexed cyclodextrins as a vehicle, whereby when the free drug (i.e., hydrocortisone) is in suspension, whereby an increase in the cyclodextrin concentration resulted in increased drug flux through the skin (pg 21). Thus, uncomplexed cyclodextrin can behave as a permeation enhancer (pg 19-21), when it is uncomplexed to the active agent (pg 21). Furthermore, cyclodextrins are described as common excipients in topical formulations, that have a role outside of only complexing active ingredients (Table 1-2, pg 19, column 1). Additionally, guest-host complexes are in equilibrium, such that free drug formation can be formed on the basis of equilibration and relative concentrations of guest and host (abstract, pg 22).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the statin hydrogel compositions of Ray to add a cyclodextrin in various amounts, as taught by Pavliv and Kerdpol, because Pavliv teaches that cyclodextrins such as hydroxy-propyl-beta-cyclodextrin complexes the statin (Pavliv – claims 4 and 5) in order to improve solubility and/or stabilize topical formulations (abstract, [0018, 0039, 0048]). Furthermore, Ray teaches the incorporation of carrier components that affect the active ingredient, such as solubilizers and stabilizers [0043], in which Pavliv describes cyclodextrins to solubilize and stabilize statin topical formulations (abstract, [0018, 0039]). Finally, Kerdpol provides structural teachings of cyclodextrin, substituted cyclodextrin, and HPbCD, that are used in pharmaceutical formulations to enhance solubility of low water-soluble compounds.
Finally, regarding claims 145-146: Loftsson teaches uncomplexed cyclodextrin to have a role in topical formulations as a permeation enhancer and/or common excipient. Ray teaches the efficacy of topical statins for wound healing alone, without complexation to a cyclodextrin, rendering this format as obvious, where cyclodextrin is functionally a regular excipient, where Ray further teaches many types of additives/excipients [0036, 0043, 0046], whereby activity of the statin relies on absorption through the skin (Ray – claim 12). Thus, when uncomplexed cyclodextrin and uncomplexed statins independently demonstrate functional beneficial activity in topical therapeutic formulations, then their combination in their uncomplexed forms is prima facie obvious.
Claims 133-152 are rejected under 35 U.S.C. 103 as being unpatentable over Ray (US20220047590A1), Pavliv (US20110257240A1), Kerdpol (Polymers, 2019), and Loftsson (Internation Journal of Pharmaceutics, 2001), as applied to claims 133-135 and 137-150, and in further view of Mustoe (US20190030045A1) and Quarfoot (US4909244A).
As discussed above, the combined Prior Art teaches topical hydrogel compositions that comprise statin and cyclodextrins for wound healing in a transdermal patch format and a method of treatment and making. However, they do not teach a cross-linked hydrogel formulations (instant claims 136 and 152) and a dressing format (instant claim 151).
Mustoe teaches compositions that comprise statins to help prevent and reduce scar formation (abstract). Furthermore, Mustoe teaches dressings [0009, 0031, 0059], whereby a dressing includes hydrogels based on cross-linked polymers (i.e., the hydrogels discussed by Ray would be typically found in a format, comprising cross-linked polymers containing about 60% water), that are impregnated with statins and other compounds (reads on instant claims 136 and 152) [0009, 0031, 0059], whereby dressings are materials applied to a wound for protection, absorbance, drainage, treatment, etc. [0009, 0031, 0059]. Thus, it would be obvious to incorporate a “crosslinker” (reads on instant claim 152) in order to make a “cross-linked polymer” taught by Mustoe. Finally, Mustoe teaches all forms of “dressing”, that comprise statins [0009, 0031, 0059].
Quarfoot provides an embodiment of a dressing that has a wound facing layer and an external layer (reads on claim 151) (abstract), as a demonstration of a typical dressing configuration (i.e., it would be an obvious embodiment of Mustoe’s generic “dressing” teachings and/or the transdermal patches of Pavliv [0048]).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel compositions comprising statins and cyclodextrins of the combined Prior Art with the dressings based on cross-linked polymers of Mustoe and Quarfoot, because Mustoe teaches ingredient impregnated dressings are useful materials applied to a wound for protection, absorbance, drainage, treatment, etc. [0031] and Mustoe and Quarfoot describe typical dressing configurations for application, which aligns with Ray’s use of statins for topical wound treatment in various topical formulation types, including hydrogel formulations [0034] and/or the transdermal patches of Pavliv [0048].
Claims 133, 137-138, and 145-147 are rejected under 35 U.S.C. 103 as being unpatentable over Senel (WO2019009823A1).
Senel teaches a composition containing atorvastatin, which is an active agent belonging to the statin group which has an anti-inflammatory effect (abstract), which is intended for application for dermal inflammatory tissue (Senel – claim 44).
Regarding claim 133 and 137-138: Senel teaches a gel composition containing a solid dispersion of atorvastatin and a carrier polymer such as gelatin and water (Senel – claims 1 and 32; pg 7, paragraph 2), whereby the solid dispersion is added to the gel composition (Senel – claim 1). Additionally, Senel teaches further incorporation of cyclodextrins (infers cyclodextrin as a class) (pg 9; bottom paragraph).
Regarding claims 145-146: There is no requirement to complex the gelatin and cyclodextrin (Senel – claim 1), although the benefits of complexation are recognized (pg 3, bottom paragraph).
Regarding claim 147: Senel teaches a method that treats dermal inflamed tissue (Senel – claim 44).
In summary, Senel teaches the elements and desirability for the components for the instant composition, as described above, and thus, its obviousness. 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.). Thus, Senel teaches the combination of art-known elements (i.e., a hydrogel composition containing a dispersion of a statin, gelatin, water, and cyclodextrins) according to their disclosed beneficial properties (i.e., anti-inflammatory properties) with the resultant product nothing more than one would expect from their combination (i.e., a method treating dermal inflammatory tissue).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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/R.P./Examiner, Art Unit 1614 8/10/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
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