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 .
Claim Status
Claims 1-7, 9, 15 and 17-24 are pending.
Claims 8, 10-14 and 16 have been canceled.
Claims 1, 9 and 17 are currently amended.
Claims 22-24 have been added.
Claims 1-7, 9, 15 and 17-24 are currently under consideration.
Claims 1-7, 9, 15 and 17-24 are rejected.
Acknowledgement of Receipt
This Office Action is in response to the Applicants’ amendments and remarks filed 12/04/2025.
Withdrawn Objections/Rejections
The objections to the specification and claims 1 and 16 are withdrawn.
In light of the new amendments and/or upon further consideration, the rejection of claim 12 under 35 U.S.C. § 112(b) is withdrawn.
In light of the new amendments and/or upon further consideration, the rejection of claim 11 under 112(d) is withdrawn.
Maintained Rejections
The following rejections are maintained from the previous Office Action dated 09/05/2025 since the art that was previously cited continues to read on the newly amended limitations.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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. Applicants are 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.
Applicant Claims
The instant claims are directed to a transdermal patch, the transdermal patch comprising: a film comprising: a biodegradable polymer; and reverse micelles encapsulating a HIF-1a potentiator complexed with polyvinylpyrrolidone (PVP), wherein the reverse micelles are present within the biodegradable polymer; and an impermeable backing membrane, wherein the film is present on the impermeable backing membrane (instant claim 1); wherein the HIF-1a potentiator comprises an iron chelator (instant claim 2); wherein the iron chelator comprises deferoxamine (DFO) (instant claim 3); wherein the DFO concentration is from at least 1% and not more than 20% as weight/weight percent of film (instant claim 4); wherein the iron chelator comprises deferasirox (instant claim 5); wherein the iron chelator comprises deferiprone (instant claim 6); wherein the biodegradable polymer comprises an ethylcellulose matrix (instant claim 7); wherein the PVP is present at a concentration of from about 5 wt% to about 25 wt% (instant claim 9); wherein the reverse micelle is stabilized by PVP (instant claim 15).
Further, Applicants claim a transdermal patch comprising: a film comprising a hydrophilic HIF-1a potentiator encapsulated in reverse micelles with a non-ionic surfactant stabilized by PVP in an ethyl cellulose matrix, wherein the hydrophilic HIF-1a potentiator is complexed with the PVP; and an impermeable backing membrane (instant claim 17); wherein the patch is prepared by dissolving the hydrophilic HIF-1a potentiator, PVP, ethyl cellulose and the non-ionic surfactant in a lower alcohol, followed by drying on a hydrophobic surface to form a film and then adhering the film to the impermeable backing membrane (instant claim 18); wherein the HIF-1a potentiator comprises an iron chelator (instant claim 19); wherein the iron chelator comprises deferoxamine (DFO) (instant claim 20); wherein the reverse micelles comprise a non-ionic surfactant (instant claim 21); wherein the non-ionic surfactant comprises a phospholipid (instant claim 22); wherein the non-ionic surfactant comprises a polysorbate (instant claim 23); wherein the polysorbate is selected from the group consisting of sorbitan monolaurate, polyoxyethylene sorbitan monooleate and polyoxyethylene sorbitan trioleate.
Claims 1-7, 9, 15 and 17-24 are rejected under 35 U.S.C. 103 as being unpatentable over Gurtner et al. (US 2010/0092546, pub. 04/15/2010) and Radovic-Moreno et al. (US 2010/0196482, pub. 08/05/2010) in view of Haaf (Polymer Journal, 17, 1, 143-152, 1985) and evidenced by Bühler (Polyvinylpyrrolidone excipients for pharmaceuticals, Springer Science & Business Media, 2005), herein Gurtner, Radovic, Haaf, and Bühler.
Gurtner discloses compositions comprising HIF-1α potentiating agent and to treat chronic skin wounds by transdermally penetrating the wound via a transdermal patch comprising thein which a provided in the transdermal patch (claims 1-2, 12). Gurtner discloses a transdermal patch that comprises an adhesive; an impermeable backing membrane; and a release liner containing HIF-1α modulator dispersed or super-saturated within a biodegradable polymer ([0089], Fig. 6A, claim 17). Gurtner teaches that the HIF-1α potentiating agent includes the heterodimer complex and the subunits thereof, HIF-1α ([0036]). Gurtner provides examples that show deferoxamine present ([0017], Fig. 2A-2C, [0021], claim 20). Gurtner discloses that the HIF-1α potentiating agent is embedded in the biodegradable polymer ([0045], [0072], [0081], [0089], claim 15); polyvinylpyrrolidone (PVP) is taught ([0082], claims 15-16).
Regarding the reverse micelles encapsulating a HIF-1α potentiator limitation of claim 1, Gurtner does not teach reverse micelles and a HIF-1α potentiator complexed with PVP.
Radovic discloses a method for encapsulating therapeutic agents (e.g., siRNA) in biodegradable polymers, whereby the agents are formulated into reverse micelles composed of naturally occurring lipids (title, abstract, [0007], [0013], claim 1). Radovic is directed to a pharmaceutical composition, wherein the therapeutic agent is encapsulated within reverse micelles ([0013], claims 1, 21); wherein the reverse micelle is encapsulated by a biodegradable polymer ([0013], claim 43); and a method in which the therapeutic agent is dissolved with an amphipathic lipid to form reverse micelles that contain the therapeutic agent, which are entrapped in the biodegradable polymer ([0013], [0020], [0023], [0042], claim 59). Applicants and the prior art teach the same biodegradable polymer (see Spec., [0015], Gurtner [0082], claim 16, Radovic [0196], claim 5). Radovic teaches that wherein nanoparticles comprise an siRNA molecule, the sequence of the siRNA molecule is complementary to hypoxia-inducible factor-1 (HIF-1) ([0161]). Radovic teaches that reverse micelles are non-toxic, and effectively entrap therapeutic agents and disperse them into a nanosuspension, facilitating their incorporation into the hydrophobic core of biodegradable polymers ([0007]).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to incorporate the reverse micelles as taught by Radovic in the composition of Gurtner with expected results. One would be motivated to do so with a reasonable expectation of success because Radovic teaches that transdermal patches have the added advantage of providing controlled delivery of a compound to the body and that such dosage forms can be made by dissolving or dispensing conjugates in a proper medium (i.e., film) ([0192]). Both references focus on target specificity (Radovic [0034]; Gurtner ([0055]). Radovic provides further motivation to incorporate reverse micelles because reverse micelles effectively entrap therapeutic agents, such as hydrophilic therapeutic agents, and disperse them into a nanosuspension, facilitating their incorporation into the hydrophobic core of biodegradable polymers ([0007]). Radovic teaches that reverse micelles improve encapsulation yield, drug-to-carrier weight ratio, and reproducibility of nanoparticle formation, without requiring the use of potentially damaging emulsification techniques ([0007]). Further, the methods of Radovic use components, or segments of components, that are naturally-derived or FDA-approved for use in humans, thereby generating clinically relevant drug delivery vehicles ([0007]).
Gurtner ([0013]) and Radovic ([0196]) teach PVP but do not teach complexation with PVP.
Haaf discloses the preparation of vinylpyrrolidone (VP) copolymers (pg. 147, col. 2, para. 2). As evidenced by Bühler, polyvinylpyrrolidone (PVP) is obtained by free-radical polymerization of vinylpyrrolidone in water or 2-propanol, yielding a chain structure (pg. 1; see section 2.1, Fig. 6) and its ability to form complexes is widely used in pharmaceuticals (pg. 2; see section 3.2.5.1).
Haaf teaches that PVP forms complexes with various compounds, especially with H-donors such as phenols and carboxylic acids (abstract, pg. 150, Table V). Haaf teaches that PVP forms complexes with numerous low molecular weight compounds as well as with many polymers and that the formation of complexes is due to hydrogen bonding (pg. 151, col. 1, see Applications). For example, Haaf teaches that in the case of PVP-iodine, the efficiency in which the complexing takes place is what contributes to a non-irritating and mild antiseptic (pg. 151, col. 2, para. 3).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to apply PVP complexing taught by Haaf evidenced by Bühler to the compositions of Gurtner and Radovic with expected results. Haaf teaches stabilization (pg. 150, Table IV) while Gurtner teaches dissolving the mixture of polymers and HIF-1 modulator drug (i.e., DFO) and drying and forming films ([0072], [0082], [0089]). One would expect that the PVP would complex with the HIF-1α potentiator given the known special and unusual properties of PVP gives it the ability to complex with various compounds (see Haaf, pg. 147, col. 1, para. 2). In addition, Radovic teaches that the target specificity of the reverse micelle of the invention will be maximized by optimizing the density of the biodegradable polymer conjugated to the targeting moiety on the reverse micelle ([0032-0034], see also [0042]).
Regarding claims 2-4 (i.e., iron chelator; DFO; 1-20%), Gurtner teaches HIF-1α potentiating agents, with DFO as an example, formulated for dosing which are embedded or dispersed in a polymer will be present at a concentration of at least about 1% and not more than about 20%, as weight/weight percent of polymer ([0043], [0045], claim 4). Gurtner provides a transdermal patch that includes an adhesive, an impermeable backing membrane, and a release liner containing HIF-1α modulator dispersed or super-saturated within biodegradable polymer ([0081] Fig. 2B, [0084], claims 12 and 15).
Regarding claims 5-6, Gurtner teaches deferasirox and deferiprone ([0012], claim 4).
Regarding claims 7 and 9, Gurtner discloses a preparation of one type of transdermal patch that includes a mixture of polymers (weighed in requisite ratios of ethyl cellulose and polyvinyl pyrrolidone) and HIF-1 modulator drug dissolved in 10 ml of chloroform and the active agent is entrapped and ratio of ethyl cellulose to PVP is 7:1 where PVP is present at about 12.5 wt.% (i.e., 350 mg ethyl cellulose; 50 mg PVP) ([0013], [0072], [0082], [0089], claims 15-16).
Regarding claim 15 (i.e., reverse micelle stabilized by PVP), as mentioned above Gurtner teaches polyvinyl pyrrolidone ([0013], [0072], [0082], [0089], claims 15, 16). Radovic teaches polyvinyl pyrrolidinone ([0196], claim 5). Applicants’ description in paragraph [0015] in the instant specification stating, “polymer matrix of polyvinylpyrrolidone (PVP) and ethylcellulose, in which the active agent is entrapped. In some such embodiments, the agent is encapsulated in a reverse micelle with a nonionic surfactant, which reverse micelle is stabilized by, for example, PVP in the matrix,” is evidence that the presence of PVP in the matrix inherently stabilizes. See MPEP § 2112.
Regarding claims 19-20, Gurtner provides examples with deferoxamine present ([0017], Figs. 2A-2C; [0021], claim 20).
Regarding non-ionic surfactant limitations of claims 17-18 and 21-22, Applicants state, “Suitable surfactants include, but are not limited to, phospholipids such as lecithin, including soy lecithin and detergents,” (see Spec., [0077]). Gurtner mirrors this by teaching, “Suitable surfactants include, but are not limited to, phospholipids such as lecithin, including soy lecithin and detergents. Preferably, the surfactant selected for application to a wound or skin surface is mild and not lead to extensive irritation or promote further tissue damage to the patient,” ([0053-0054]). Radovic teaches that as lecithin is a natural lipid, it is readily available e.g., from soybean, and is FDA approved for use in other delivery devices ([0020], [0039]). Applicants describe nonionic surfactants as providing for the formation of reverse micelles to aid in delivery of active agent and that suitable surfactants include lecithin (see Spec., [0079]). Radovic teaches that the amphipathic component used to form the reverse micelle is lecithin and is neutral (i.e., non-ionic) ([0014], [0020], [0039], claims 28, 29).
Regarding claims 23-24, Applicants disclose polysorbate 80 (Tween 80) and sorbitan monolaurate 20 (Span 20) as nonionic surfactants added for reverse micelle formation (see Spec., [00162]). Gurtner teaches sorbitan monolaurate as a permeation enhancer ([0058]). Radovic teaches TWEEN™ 80 (i.e., Polysorbate 80, polyoxyethylene sorbitan monooleate) ([0187]).
Response to Arguments
Applicants’ arguments have been fully considered but they are not persuasive.
Applicants argue that Gurtner solely teaches use of PVP polymer in combination with ethylcellulose polymer as a matrix of biodegradable polymers to form the release liner citing paragraph [0072] of Gurtner (see Remarks, pg. 8, last paragraph). Applicants cite paragraph [0032] to argue that Radovic is directed to polymer-encapsulated reverse micelles, rather than the reverse micelle encapsulating the biodegradable polymer(s) and solely teaches use of PVP as a 'binder' external to the reverse micelles (see Remarks, bridging pgs. 8-9).
The Examiner respectfully asserts that Haaf evidenced by Buhler are provided to teach the complexation of the HIF-1α with PVP. Radovic meets the reverse micelles encapsulating a HIF-1α potentiator limitation by disclosing a pharmaceutical composition wherein the therapeutic agent is encapsulated within reverse micelles ([0013], claims 1, 21).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., reverse micelle encapsulating the biodegradable polymer(s)) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Radovic is cited to teach reverse micelles. Radovic does not exclude the presence of PVP within the reverse micelles. Gurtner teaches a mixture polymers and HIF-1 modulator drug; drying and forming films ([0072]). PVP complexes with various active agents are very well known in this art. Haaf and Buhler demonstrate that polyvinyl pyrrolidone (PVP) forms complexes with various compounds (abstract, pg. 150, Tables IV-V).
Here the prior art, by teaching stabilization indicates and establishes the already present need for component(s) to achieve stability. MPEP § 2144(IV) states "it is not necessary in order to establish a prima facie case of obviousness . . . that there be a suggestion or expectation from the prior art that the claimed [invention] will have the same or a similar utility as one newly discovered by applicant," and concluded that here a prima facie case was established because "[t]he art provided the motivation to make the claimed compositions in the expectation that they would have similar properties."
For these reasons, Applicants’ arguments are found unpersuasive.
Conclusion
All claims under consideration remain rejected; no claims are allowed. 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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 900-500 ET.
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/Karen Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614