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 .
Status of Action/Claims
Receipt of remarks, filed on 3/13/2026, is acknowledged. Claims 16-19 and 25-37 are currently pending. Claims 28-34 have been withdrawn. Accordingly, claims 16-19, 25-27 and 35-37 are currently under examination.
Rejection(s) not reiterated from the previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
Maintained Claim(s) Rejection(s)/Objection(s)
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 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.
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.
Claims 16-19, 25-27 and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (Adv Drug Deliv Rev. 2016 December 15; 107: 176-191) in view of Landau (EP 1911472A1; Apr. 16, 2008) as evidenced by and Matsuura (Scientific Reports, 5:15545, Oct. 2015) and Knoebl (Biologics: Target & Therapy 2008:2(2) 285-296).
Lee throughout the reference teaches polylactic acid (PLA) micro and nano particles which are used for various biomedical applications because of its biodegradable, biocompatible, and nontoxic properties.
Regarding claims 16, 25, 26, 27, 35 and 37, Lee teaches PLA micro and nano particle formulations used as controlled drug delivery systems of therapeutic molecules including protein drugs. Lee teaches various techniques, such as melting technique, to encapsule the drug into the polymer (PLA). The active pharmaceutical ingredient/drug is dispersed homogenously within the PLA matrix. Lee teaches one of the advantages of using PLA to make micro and nano-particles is the flexibility. Physical properties, such as size and shape, and chemical properties, including molecular weight, can be easily controlled to obtain desirable pharmacokinetic and biodegradable properties. Lee disclose Resomer R207 (PLA, average MW 209,000) polymers which reads on the MW of the PLA recited in instant claims. Lee discloses protein C as a drug which is used in the formulation with PLA. As evidenced by Knoebl, protein C has a molecular weight of about 62 kD (e.g. page 286). Also, as evidenced by Matsuura, the heat denaturation of proteins (e.g., protein C) is usually irreversible at temperatures higher than 80 C. Therefore, inclusion of protein C taught by Landau reads on the composition comprising a drug having a denaturation temperature below 120 C. Regarding the claimed limitation wherein the drug delivery composition is produced by a method that incorporates said drug and said enzyme in said polymer-based matrix during heat treatment at a temperature T at which the polymer is in a totally molten state, Lee teaches the melting technique provides another option for encapsulating drugs into polymers. The melting process avoids the use of organic solvents, but the drug is dispersed in a polymer melt. The resulting drug/polymer melt is solidified by a cooling water phase or a cooling chamber with dry air flow. The drug/polymer melt is cooled down and then ground or milled to form particles. Thus, Lee teaches a similar method of producing the formulation as recited in instant claim 16. Further, the claims are directed to a product. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). (see e.g., Abstract; Introduction; sections 2-4; Figures and Tables; Entire Document).
Regarding claim 17, Lee discloses the PLA formulation comprising 10% drug and 40% PLA polymer.
Lee does not teach the PLA formulation further comprises a polymer degrading enzyme and the amount thereof recited in the instant claims. However, Landau cures this deficiency.
Landau also teaches drug delivery compositions comprising a drug (a pharmaceutical agent) and a polymer-degrading enzyme (degradation additive) embedded into a polymer based matrix. The encapsulated degradation additive is conducive for accelerating degradation of the structures or components of the medical device for achieving a desired mass loss through accelerated degradation after the medical device has achieved its desired functional effect or achieved the end of its functional purpose or useful life. Landau teaches proteinase K (i.e., protease enzyme) as the degradation additive. Landau teaches the biodegradable and/or bioabsorbable material polymers and the degradation additive and the drug are mixed at a temperature suitable for the polymers until uniform dispersion is obtained of the degradation additive and drug. Landau teaches that selection of the enzyme or degradation additive is based on the type of material that needs to be degraded and that the degradation of the encapsulation polymer coincides with the desired drug release profile. The reference also teaches that the amount of degradation additive will depend on various parameters which include deliverability. (see e.g., claims; summary of invention; Para 0009, 0021, 0059, 0063, 0080, 0122; Figs 6-9; Entire document).
It would have been prima facie obvious to one of ordinary skill in the art to have modified Lee to incorporate the teachings of Landau and further include a polymer-degrading enzyme which is embedded and homogeneously distribute into the polymer based matrix (PLA) of Lee. As discussed supra, Landau also teaches drug delivery compositions comprising a drug (a pharmaceutical agent) and a polymer-degrading enzyme (degradation additive) embedded and uniformly dispersed into a polymer based matrix. Landau teaches the encapsulated degradation additive is conducive for accelerating degradation of the structures or components of the medical device for achieving a desired mass loss through accelerated degradation after the medical device has achieved its desired functional effect or achieved the end of its functional purpose or useful life. Lee disclose the PLA micro and nano particles for use as implants and controlled release and it would been obvious to one skilled in the art to include the polymer degrading enzyme for accelerating degradation of the structures or components of the implant for achieving a desired mass loss through accelerated degradation after the implant has achieved its desired functional effect or achieved the end of its functional purpose or useful life.
Further, it would have obvious to one skilled in the art to optimize the amount of the polymer degrading enzyme because Landau teaches that the amount of degradation additive will depend on various parameters which include deliverability. Landau teaches that selection of the enzyme or degradation additive is based on the type of material that needs to be degraded and that the degradation of the encapsulation polymer coincides with the desired drug release profile. Thus, one skilled in the art would have found it obvious to determine the amount based on parameters such as drug deliverability, drug release profile and the optimal amount needed to degrade the polymer.
Regarding the amount of polymer based matrix and the drug recited in claim 17, as discussed supra, Lee discloses the PLA formulation comprising 10% drug and 40% PLA polymer. As discussed supra, Lee teaches one of the advantages of using PLA to make micro and nano-particles is the flexibility. Physical properties, such as size and shape, and chemical properties, including molecular weight, can be easily controlled to obtain desirable pharmacokinetic and biodegradable properties. Thus, it would have been obvious to one skilled in the art to determine an amount of the PLA polymer based on the desired release profile and biodegradable properties. Further, regarding the amount of active drug, it would have been obvious to include an amount which is needed based on parameters such as the type of disease being treated, size of the subject, etc. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With respect to the instantly claimed recitation wherein the polymer degrading enzyme is suitable for depolymerizing PLA of the polymer based matrix, the Landau reference teaches the instantly claimed polymer degrading enzyme and thus would necessarily be capable of depolymerizing PLA of the polymer based matrix.
Regarding the claimed limitation wherein the composition “consists of”, as discussed supra, the formulation of Lee in view of Landau does not require additional components which are excluded from the consisting of language recited in the claims.
From the combined teaching of the cited reference, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant argued that protein C in Lee et al. is incorporated into PLA by using a double emulsion technique and not a hot melt technique. It was argued that only actives incorporated using a melt technique are small molecules with molar mass below 400 g/mol. These compounds are used in hot melt methods because they are stable at high temperatures whereas proteins, such as protein C are temperature sensitive. Thus, one skilled in the art would not have used protein C in a high temperature technique.
In response, as discussed supra, the instant claims are directed to a product. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The prior art references cited above render obvious the instantly claimed components, including a drug having a denaturation temperature below 120 C, the amounts of the component contained in the composition and the structure of the composition recited in the claims and therefore read on the instantly claimed composition. Thus, while the prior art may teach away from using high temperature processes for thermosensitive drugs, the composition taught by Landau is structurally the same as the composition recited in the instant claims and therefore applicant’s argument are not found persuasive.
Applicant argued that while Landau suggests including an enzyme and an active ingredient in the same polymeric device, they are each contained in a separate polymer. This is essential to achieve the desired differentiated degradation effect desired by Landau. In contrast, in the present invention, both the active ingredient and the enzyme are homogenously distributed and embedded into the PLA matrix.
In response, Landau in figure 9 discloses the enzyme 95 and the drug 99 contained within the same polymer 75. Thus, contrary to applicant’s argument, Landau does disclose that the enzyme and the active ingredient can be contained within the same polymer. Further, while Landau teaches there being two polymers, the examiner argues that Lee is utilized as the primary reference which requires only one polymer and Landau is utilized as a secondary reference for its teachings of including a degradation additive in the polymer based matrix to accelerate degradation of the structures or components of the medical device after the medical device has achieved its desired functional effect or achieved the end of its functional purpose or useful life. Lee disclose the PLA micro and nano particles for use as implants and controlled release and it would been obvious to one skilled in the art to include the polymer degrading enzyme for accelerating degradation of the structures or components of the implant for achieving a desired mass loss through accelerated degradation after the implant has achieved its desired functional effect or achieved the end of its functional purpose or useful life. Inclusion of a polymer degrading enzyme in the polymeric matrix to degrade the polymer for controlled release of drug and/or degradation of the polymer after the polymer has completed its purpose was known in the art as disclosed by Landau. As such, one skilled in the art would have found it prima facie obvious to include a polymer degrading enzyme in the polymeric matrix (PLA) of Lee’s formulation.
Conclusion
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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/A.S/ Examiner, Art Unit 1616
/SUE X LIU/ Supervisory Patent Examiner, Art Unit 1616