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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on July 2, 2026 is acknowledged. The traversal is on the grounds that Group I and II share a technical relationship that is special [pg 9 pgh 1]. Cho et al. and Ramtoola et al. do not teach disclose the advantageous properties of the specific combination of a cyclosporin 3-position derivation and its excellent interaction with PLGA [pg 8 pgh 4]. The composition in the instant specification shows extended release without initial burst, while Ramtoola shows an undesirable initial burst [pg 8]. This is not found persuasive because the special technical features upon which applicant relies (i.e., release without initial burst and particles prepared according to examples 39 to 42) 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).
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election without traverse of [2-methylthio-sarcosine] cyclosporine A and PLGA in the reply filed on July 2nd, 2026, is acknowledged.
Claims 56-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on July 2, 2026.
Priority
The instant application claims priority to 371 National Stage Application PCT/KR2022/095079, filed April 7, 2022, under 35 U.S.C. 119(a)-(d), and foreign applications KR10-2021-0076648, filed June 14, 2021 and KR10-2022-0008307, filed Janurary 20, 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The priority date of June 14, 2021 is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) filed on December 13th, 2023, February 26, 2025, and January 27, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claims Status
The claims listing filed on July 2, 2026 is pending. Claims 56-62 are withdrawn from further consideration for the reasons set forth in the restriction requirement, 37 CFR 1.142(b). Claims 43-55 are being examined on the merits in this office action.
Claim Objections
Claim 55 is objected to under 37 CFR 1.75(i) because of the following informalities: there should be an indentation between “wherein” and “the aqueous vehicle” because it the claim has a plurality of elements and it the aqueous vehicle in an independent element.
Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation [37 CFR 1.75(i)].
Appropriate correction is required.
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.
The following prior art rejections are based on the election of [2-methylthio-sarcosine] cyclosporine A and PLGA in the reply filed on July 2, 2026.
Claims 43-48 and 50-55 are rejected under 35 U.S.C. 103 as being unpatentable over Seaman et al. (US20190054023A1) and Kim et al. (US6762164B2; published 2004).
Seaman et al. provide a controlled release pharmaceutical formulation comprising cyclosporine-loaded microparticles of a bioresorbable polymer [Abstract]. Seaman et al. specifically claim a controlled release pharmaceutical formulation comprising cyclosporine-loaded microparticles of a bioresorbable polymer comprising poly (D, L-lactide) or poly (D, L-lactide-co-glycolide) and a thixotropic agent [claims 1-2]. Seaman et al. does not teach the formulation with 3-substituted cyclosporine derivative [2-methylthio-sarcosine3] cyclosporine A in place of cyclosporine.
Kim et al. disclose a method for treating alopecia and promoting hair growth comprising treating a patient in need thereof with a pharmaceutical composition containing [D-2-methylthio-sarcosine3] cyclosporin A as an active ingredient [claims 1-2]. It would have been obvious to one of ordinary skill, prior to the effective filing date, to add [D-2-methylthio-sarcosine3] cyclosporin A as the cyclosporin in Seaman et al.’s formulation because it constitutes simple substitution of one known element for another to obtain predictable results [MPEP § 2143.01(B)]. The relevant findings for this rationale are as follows:
The prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components. In the instant case, the primary reference teaches a controlled-release formulation which differs from the claimed controlled-release particle by the substitution of [2-methylthio-sarcosine3] cyclosporine A for cyclosporine. Therefore, prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components.
The substituted components and their functions were known in the art. The function of [2-methylthio-sarcosine3] cyclosporine A is known in the art because Kim et al. teach its use in a method for treating hair loss. Therefore, the substituted components and their functions were known in the art.
One of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. One of ordinary skill in the art would expect that the [2-methylthio-sarcosine3] cyclosporine A can be used in place cyclosporine in the combination because [2-methylthio-sarcosine3] cyclosporine A is simply a derivative of cyclosporine. Therefore, one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable.
Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. Kim et al.’s [2-methylthio-sarcosine3] cyclosporine A is geared towards a method of treating hair loss. One of ordinary skill in the art would find it obvious to perform the substitution to use the Seaman’s controlled release particle to treat hair loss.
Regarding claim 44, Seaman et al. specify that the “ratio of lactide to glycolide co-monomers in the final mixture of polymers (“the L:G ratio”) may influence the rate of bioresorption and therefore the release characteristics of the cyclosporine over time. In certain cases, the L:G ratio may be in the range 60:40 to 95:5, for example within the range 70:30 to 80:20” [0017]. Seaman’s teachings greatly overlap with the instant ratio of 90:10 to 40:60.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) [MPEP 2144.05].
Therefore, prior to the effective filing date, it was prima facie obvious to use a molar ratio of lactide to glycolide of 90:10 to 40:60 to obtain preferential bioresorption rates and cyclosporine release characteristics.
Regarding claim 45, Seaman et al. specify the formulation used in the synthesis of CsA-encapsulated microspheres [0080]. Acid-terminated poly (D, L-lactide-co-glycolide) with a lactide to glycolide ratio of 75 to 25 and molecular weight of 4000 to 15000 Da was used [0081]. One of ordinary skill in the art recognizes that an acid-terminated polymer has a carboxylic acid (negative charge) end group. Therefore, prior to the effective filing date, it was obvious to use a PLGA with carboxylic acid end group for a reasonable expectation of making a successful controlled release particle as per Seaman et al.’s teachings.
Regarding claim 46, Seaman et al. specify the formulation used in the synthesis of CsA-encapsulated microspheres [0080]. Acid-terminated poly (D, L-lactide-co-glycolide) with a lactide to glycolide ratio of 75 to 25 and molecular weight of 4000 to 15000 Da was used [0081]. The molecular weight range of PLGA is encompassed by the instant range [MPEP 2144.05]. Therefore, prior to the effective filing date, it was prima facie obvious to use a PLGA with a molecular weight of 4000 Da to 240000 Da for a reasonable expectation of making a successful controlled release particle as per Seaman et al.’s teachings.
Regarding claim 47, Seaman et al. specify the formulation used in the synthesis of CsA-encapsulated microspheres [0080]. 150 mg of Acid-terminated poly (D, L-lactide-co-glycolide) and acid-terminated (poly (D, L-lactide) and 75 mg of cyclosporin A were used [0081]. This translates to a cyclosporine to biodegradable polymer ratio of 20 to 80 by weight, encompassed by the instant range [MPEP 2144.05]. Seaman claims controlled release pharmaceutical formulation wherein the bioresorbable polymer is poly (D, L-lactide-co-glycolide) [claim 2]. Therefore, prior to the effective filing date, it was obvious one of ordinary skill in the art to replace poly (D, L-lactide-co-glycolide) and acid-terminated (poly (D, L-lactide with only PLGA as a biodegradable polymer in a weight ratio taught by Seaman et al. because Seaman et al. teaches it is possible to only use PLGA as the polymer with cyclosporin in a controlled-release polymer.
Regarding claim 48, Seaman’s claimed controlled release pharmaceutical formulation comprises cyclosporine-loaded microparticles with a mean diameter in the range 20 μm to 40 μm, encompassed by the instant range [MPEP 2144.05].
Regarding claim 50, Kim et al. discloses a method of treating alopecia and promoting hair growth comprising treating a patient in need thereof with a pharmaceutical composition containing D-2-methylthio-sarcosine cyclosporin A [claims 1 and 2].
Regarding claim 51, Kim et al. evidence that alopecia refers to a phenomenon wherein duration of the anagen growth phase is shortened and the percentage of hairs in the catagen and telogen phases increases, whereby the number of lost hairs is increased excessively and abnormally [Col 1 line 24]. Kim also mentions the possible development of cyclosporin as a hair regrowth agent in human alopecia areata [Col 3 line 3]. Therefore, one of ordinary skill in the art would find it obvious to apply a controlled release particle comprising [2-methylthio-sarcosine3] cyclosporin A to treat autoimmune alopecia areata.
Furthermore, these are recitations of intended use that do not impart any structural changes to the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claim 52, Seaman et al. claim the controlled release pharmaceutical formulation in an injectable form [claim 16]. Seaman et al. does not teach an intralesional, intradermal, or subcutaneous administration. However, these are recitations of intended use that do not impart any structural changes to the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art to patentably distinguish the claimed invention from the prior art. If the prior art structure can perform the intended use, then it meets the claim. Seaman et al.’s injectable formulation using Kim et al.’s [2-methylthio-sarcosine3] cyclosporin A is capable of being applied intralesionally, intradermally, or subcutaneously.
Regarding claim 53, Seaman et al. claim the controlled release pharmaceutical formulation in an injectable form [claim 16]. One of ordinary skill in the art would find it obvious to formulate the composition as a topical injection because Seaman’s formulation is also taught for use in hair loss and alopecia. Furthermore, formulating an injection for topical, depot or dermal use is an intended use recitation. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art to patentably distinguish the claimed invention from the prior art. If the prior art structure can perform the intended use, then it meets the claim. In the instant case, Seaman’s formulation is capable of topical, depot, or dermal use because it is also an injectable form, which is liquid.
Regarding claims 54 and 55, Seaman et al. claims the formulation of cyclosporine-loaded microparticles comprising mannitol (isotonic agent), phosphate buffered saline ((aqueous vehicle), polysorbate 80 (suspending agent), hydroxyethyl cellulose (suspending agent), and hypromellose [claims 1, 14, and 52-53].
Claims 43-53 are also rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi et al (Takeuchi, Issei et al. "Skin permeability and transdermal delivery route of 30-nm cyclosporin A-loaded nanoparticles using PLGA-PEG-PLGA triblock copolymer." Colloids and Surfaces A 600, (2020): 124866) and Kim et al. (US6762164B2; published 2004).
Takeuchi et al. teach that PLGA has been widely used and studied as a class of biodegradable polymers for pharmaceutical use due to their biocompatibility and biodegradability [pg 2 pgh 1 line 17]. In the region of transdermal delivery, it improves the permeability of medical agents, protects unstable agents in the particles, and controls the release of the active agent from the carrier, elucidating its use as a control release agent. Takeuchi et al. prepare 30 nm CsA-loaded nanoparticles using PLGA, among other polymers and copolymers [pg 2 pgh 4 line 1]. Takeuchi et al. does not teach the formulation with the 3-substituted cyclosporine derivative [2-methylthio-sarcosine3] cyclosporine A in place of cyclosporine.
Kim et al. disclose a method for treating alopecia and promoting hair growth comprising treating a patient in need thereof with a pharmaceutical composition containing [D-2-methylthio-sarcosine3] cyclosporin A as an active ingredient [claims 1-2]. It would have been obvious to one of ordinary skill, prior to the effective filing date, to add [D-2-methylthio-sarcosine3] cyclosporin A as the cyclosporin in Takeuchi et al’s formulation because it constitutes simple substitution of one known element for another to obtain predictable results [MPEP § 2143.01(B)]. The relevant findings for this rationale are as follows:
The prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components. In the instant case, the primary reference teaches a controlled-release formulation which differs from the claimed controlled-release particle by the substitution of [2-methylthio-sarcosine3] cyclosporine A for cyclosporine. Therefore, prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components.
The substituted components and their functions were known in the art. The function of [2-methylthio-sarcosine3] cyclosporine A is known in the art because Kim et al. teach its use in a method for treating hair loss.
One of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable. One of ordinary skill in the art would expect that the [2-methylthio-sarcosine3] cyclosporine A can be used in place cyclosporine in the combination because [2-methylthio-sarcosine3] cyclosporine A is simply a derivative of cyclosporine.
Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. Kim et al.’s [2-methylthio-sarcosine3] cyclosporine A is geared towards a method of treating hair loss. One of ordinary skill in the art would find it obvious to perform the substitution to use the Takeuchi’s nanoparticle to treat hair loss.
Regarding claim 44, Takeuchi et al. use PLGA with a lactic acid to glycolic acid ratio of 75 to 25, within the instant ratio of 90:10 to 40:60 [pg 2 pgh 3 line 1].
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) [MPEP 2144.05].
Therefore, prior to the effective filing date, it was prima facie obvious to use a molar ratio of lactide to glycolide of 90:10 to 40:60 to obtain preferential bioresorption rates and cyclosporine release characteristics.
Regarding claim 45, Takeuchi et al. state that the zeta potential of PLGA nanoparticles showed a strong negative charge due to the presence of the terminal carboxyl group [pg 3 pgh 9 line 6]. Therefore, prior to the effective filing date, it was obvious to use a PLGA with carboxylic acid end group for a reasonable expectation of making a controlled release particle as per Takeuchi et al.’s teachings.
Regarding claim 46, Takeuchi et al. use PLGA with a molecular weight of 10000 in their CsA-loaded nanoparticle preparation [pg 2 pgh 3 line 1], encompassed by the instant range [MPEP 2144.05]. Therefore, prior to the effective filing date, it was prima facie obvious to use a PLGA with a molecular weight of 4000 Da to 240000 Da for a reasonable expectation of making a successful controlled release particle as per Takeuchi et al.’s teachings.
Regarding claim 47, in Takeuchi et al.’s CsA-loaded nanoparticle preparation, 75.2 mg of PLGA and 4.8 mg of CsA were used [pg 2 pgh 4 line 3]. This translates to a cyclosporine to biodegradable polymer range of 6 to 94 by weight, encompassed by the instant range [MPEP 2144.05]. Therefore, prior to the effective filing date, it was prima facie obvious to use a weight ratio taught by Takeuchi et al to make a controlled release particle.
Regarding claim 48, Takeuchi’s CsA-loaded nanoparticle preparation have a mean diameter of 30 nm or 0.03 µm, encompassed by the instant range [MPEP 2144.05].
Regarding claim 49, the zeta potential of Takeuchi’s CsA-loaded nanoparticles using PLGA is −46.1 ± 10.8 mV, within the instant range of -2 mV or less.
Regarding claim 50, Takeuchi does not teach 2-methylthio-sarcosine cyclosporin A. Kim et al. discloses a method of treating alopecia and promoting hair growth comprising treating a patient in need thereof with a pharmaceutical composition containing D-2-methylthio-sarcosine cyclosporin A [claims 1 and 2]. Therefore, prior to the effective filing date, it would have been obvious to add 2-methylthio-sarcosine cyclosporin in place of cyclosporin in Takeuchi’s nanoparticle to treat alopecia.
Regarding claim 51, Kim et al. evidence that alopecia refers to a phenomenon wherein duration of the anagen growth phase is shortened and the percentage of hairs in the catagen and telogen phases increases, whereby the number of lost hairs is increased excessively and abnormally [Col 1 line 24]. Kim et al. also teaches the possible development of cyclosporin as a hair regrowth agent in human alopecia areata [Col 3 line 3]. Therefore, one of ordinary skill in the art would find it obvious to apply a controlled release particle comprising [2-methylthio-sarcosine3] cyclosporin A to treat autoimmune alopecia areata.
Regarding claim 52, Takeuchi et al. does not teach an intralesional, intradermal, or subcutaneous injection. However, these are recitations of intended use that do not impart any structural changes to the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Takeuchi’s nanoparticle can be administered as an injection.
Regarding claim 53, Takeuchi et al. does not teach the composition formulated as a topical injection, a depot injection, or a dermal implant. However, these are recitations of intended use that do not impart any structural changes to the composition. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Takeuchi’s nanoparticle can be administered as an injection.
Conclusion
Claim 55 is objected to. Claims 43-55 are rejected under 35 U.S.C. 103.
Correspondence
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/SACHI JAUHARI/ Examiner, Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/ Primary Examiner, Art Unit 1654
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