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 .
Formal Matters
Applicant’s response in the reply filed on 25 November 2025 are acknowledged and have been fully considered. Claims 1-20 are pending. Claims 1-10 are under consideration in the instant office action. Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claims.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 16 October 2024 is noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
Election/Restrictions
Applicant's election of Group I (claims 1-10) in the reply filed on 25 November 2025 is acknowledged. Additionally, Applicant’s election of buprenorphine as the species of drug and the combination of poly(lactide-co-glycolide) and poly(ε-caprolactone) as the one or more biodegradable polymer in the reply filed on 25 November 2025 is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Objections
Claims 2-10 are objected to because of the following informalities: Claim 1 recites “A biodegradable implantable formulation”. However, claims 2-10 in their preamble recite “The biodegradable formulation”. For consistency reasons, the examiner recommends the preambles of claims 2-10 respectively to recite “The biodegradable implantable formulation”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: Claim 8 is objected to because the claim’s inconsistent capitalization of the first letter of several but not all of the listed biodegradable polymers. Furthermore, the claim recites “and any combination of any of these” which is awkward and unnecessarily wordy. The examiner recommends the phrasing “and combinations thereof.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “essentially free of” in claim 1 is a relative term which renders the claim indefinite. The phrase “essentially free of” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, does “essentially free” mean zero pores, less than 1% porosity by volume, or no pores larger than a certain size (e.g., 1 mm)? The specification provides no quantitative threshold or boundary to clearly determine the metes and bounds of the phrase.
For prior art rejection purposes, the examiner afforded the claim the broadest reasonable interpretation (BRI) in which not all pores are excluded.
Claims 2-9 carry the indefinite phrase “essentially free of” and do not clarify the issue. Therefore, the claims are included in the rejection for depending from an indefinite base claim.
Claim 2 recites “The biodegradable formulation of claim 1, that comprises about 40 to 80% by weight of drug.” Claim 3 recites “The biodegradable formulation of claim 1, that comprises about 50 to 70% by weight of drug. Claim 6 recites The biodegradable formulation of claim 1, that comprises about 20 to 60% by weight of biodegradable polymer. Claim 7 recites “The biodegradable formulation of claim 1, that comprises about 30 to 50% by weight of biodegradable polymer.” The amount recitations in claims 2, 3, 6, and 7 respectively renders the claim indefinite because they lack a clear reference point for the percentages. It is unclear what the respective percentages are measured relative to-e.g., the total weight of the formulation, the weight of biodegradable polymers, the weight of the drug, or the weight of an excipient or solvent (if present), or some other basis. The specification does not provide a definition or standard for interpreting this limitation, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the claims. For prior art rejection purposes, the amounts are interpreted with respect to the total weight of the composition.
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.
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.
Note: The claims are examined with respect to the elected species wherein buprenorphine as the species of drug and the combination of poly(lactide-co-glycolide) and poly(ε-caprolactone) as the one or more biodegradable polymer.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Ravis et al. (WO 2013/126552) in view of Marra et al. (US Patent No. 6,165,486).
Applicants’ claims
Applicants claim a biodegradable implantable formulation comprising buprenorphine (elected species) and combination of poly(lactide-co-glycolide) and poly(ε-caprolactone) (elected species), wherein the formulation is essentially free of pores. Dependent claims thereof recite further limitations defining various features.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Ravis et al. teach a stable nanoparticle composition comprising buprenorphine and at least one biodegradable polymer (see claim 1). The stable nanoparticle composition of claim 1, wherein the biodegradable polymer is selected from the group consisting of polycaprolactone (PCL), polyglycolic acid (PGA), poly(DL)-lactide (PLA), poly(DL)-lactide-co-glycolide (PLGA), or mixtures thereof (see claim 2). The stable nanoparticle compositions, pharmaceutical formulations, and methods comprising buprenorphine according to the present disclosure provide several advantages compared to other compositions, formulations, and methods known in the art. First, the stable nanoparticle compositions are able to provide sustained or prolonged release of buprenorphine. In particular, the stable nanoparticle compositions are capable of releasing buprenorphine over several days, weeks, or months following administration. In comparison, most currently available sustained or extended release dosage forms of buprenorphine can only release the drug over one or two days (see page 2, lines 6-13). Second, the stable nanoparticle compositions of buprenorphine utilize biodegradable polymers capable of degrading into non-toxic components in the body of an animal and may be excreted in the urine of the animal following their metabolism in the body. Accordingly, the stable nanoparticle compositions can advantageously provide sustained release of buprenorphine in the body after a single administration without the need for surgical removal of implanted matrices subsequent to depletion of the drug ((see page 2, lines 14-19). The examiner notes that according to the above teachings the stable nanoparticles composition can be implanted.
The stable nanoparticle composition of clause 1, wherein stable nanoparticle composition comprises more than one biodegradable polymer (see clause 7). The stable nanoparticle composition of clause 7, wherein the stable nanoparticle composition comprises two biodegradable polymers (see clause 8). The stable nanoparticle composition of any one of clauses 7 to 26, wherein one biodegradable polymer is PLGA (see clause 27). The stable nanoparticle composition of any one of clauses 7 to 27, wherein one biodegradable polymer is PCL (see clause 28).The stable nanoparticle composition of any one of clauses 1 to 31 , wherein the ratio of buprenorphine: polymer is about 1 : 1 (see clause 36) (which the examiner notes this is equivalent to 50% buprenorphine and 50% polymer containing composition by % weight). The stable nanoparticle composition of any one of clauses 1 to 63, wherein the stable nanoparticle composition has a release profile of buprenorphine of at least 3 months (see clause 73). Ravis et al. teach in Figure 1 and Figure 2 as follows:
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Based on the above images, the stable nanoparticle composition of Ravis et al. are free of pores and there is no mention of pore formations or the use of any pore forming agents in the composition during preparation in the entire disclosure of Ravis et al.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Ravis et al. as described above clearly teach polycaprolactone as one of the biodegradable polymers. However, Ravis et al. is silent with regard to the specific species poly(ε-caprolactone). These deficiencies are cured by the teachings of Marra et al.
Marra et al. teach Blends of biodegradable polymers, preferably poly(caprolactone) and poly(D,L-lactic-co-glycolic) acid are discussed as well as their applications in the medical field, particularly with regard to bone tissue engineering. Preferably, hydroxyapatite ("HA") granules are incorporated into the blends and the resulting blends have desirable mechanical, physical, and biological characteristics. Even more preferably the compositions of the present invention are utilized to form osteoconductive composites that supported bone cell growth on the surface as well as throughout the scaffold (see abstract). Biodegradable materials have been developed for use as implantable prostheses, as pastes, and as templates around which the body can regenerate various types of tissue. Polymers which are both biocompatible and resorbable in vivo are known in the art as alternatives to autogenic or allogenic substitutes. These resorbable biocompatible polymers include both natural and synthetic polymers. Natural polymers are typically absorbed by enzymatic degradation in the body, while synthetic resorbable polymers typically degrade by a hydrolytic mechanism. Synthetic resorbable polymers which are typically used to manufacture medical devices include homopolymers such as poly(glycolide), poly(lactide), poly(ε-caprolactone), poly(trimethylene carbonate) and poly(p-dioxanone) and copolymers such as poly(lactide-co-glycolide), poly(ε-caprolactone-co-glycolide), and poly(glycolide-co-trimethylene carbonate). The polymers may be statistically random copolymers, segmented copolymers, block copolymers, or graft copolymers or combinations of any of the above (see column 1, lines 25-42).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Ravis et al. by utilizing poly(ε-caprolactone) because Marra et al. teach blends of biodegradable polymers, preferably poly(caprolactone) and poly(D,L-lactic-co-glycolic) acid are discussed as well as their applications in the medical field, particularly with regard to bone tissue engineering. Preferably, hydroxyapatite ("HA") granules are incorporated into the blends and the resulting blends have desirable mechanical, physical, and biological characteristics. Even more preferably the compositions of the present invention are utilized to form osteoconductive composites that supported bone cell growth on the surface as well as throughout the scaffold (see abstract). One of ordinary skill in the art would have been motivated to utilize poly(ε-caprolactone) because Marra et al. teach that biodegradable materials have been developed for use as implantable prostheses, as pastes, and as templates around which the body can regenerate various types of tissue. Polymers which are both biocompatible and resorbable in vivo are known in the art as alternatives to autogenic or allogenic substitutes. These resorbable biocompatible polymers include both natural and synthetic polymers. Natural polymers are typically absorbed by enzymatic degradation in the body, while synthetic resorbable polymers typically degrade by a hydrolytic mechanism. Synthetic resorbable polymers which are typically used to manufacture medical devices include homopolymers such as poly(glycolide), poly(lactide), poly(ε-caprolactone), poly(trimethylene carbonate) and poly(p-dioxanone) and copolymers such as poly(lactide-co-glycolide), poly(ε-caprolactone-co-glycolide), and poly(glycolide-co-trimethylene carbonate). The polymers may be statistically random copolymers, segmented copolymers, block copolymers, or graft copolymers or combinations of any of the above (see column 1, lines 25-42). The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.). Furthermore, in the case where any measurable parameters such as concentrations and amounts of drug and other ingredients" 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). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in concentration or measurable parameters will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Ravis et al. and Marra et al. because both references are drawn to compositions containing drugs and biodegradable polymers for a sustained release of active agents.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4-5, 6, and 8-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6, 8, and 11 of copending Application No. 19/250,827 (herein after ‘827). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-6, 8, and 11 anticipate the claims of 1-2, 4-5, 6, and 8-9 of the instant application as explained below. This is anticipatory type double patenting rejection.
Claim 1 recites “A biodegradable implantable formulation comprising a drug and one or more biodegradable polymers, wherein the formulation is essentially free of pores.”
Corresponding claim 1 of ‘827 recites “A compacted biodegradable formulation comprising: a drug and one or more biodegradable polymers, wherein the formulation is essentially free of interconnected pores, and wherein the drug is a small molecule, a peptide, a protein, or a nucleic acid.” and claim 3 of ‘827 recites “The biodegradable formulation of claim 2, wherein the drug is a small molecule.” Claim 11 of ‘827 recites “The biodegradable formulation of claim 10, wherein the formulation is injectable.” These are species of the generic claim recited in claim 1 of the instant application.
Claim 2 recites “The biodegradable formulation of claim 1, that comprises about 40 to 80% by weight of drug.”
Corresponding claim 2 of ‘827 recites “The biodegradable formulation of claim 1, comprising about 40% to about 80% by weight of the drug.”
Claim 4 recites “The biodegradable formulation of claim 1, wherein the drug is buprenorphine.” Claim 5 recites “The biodegradable formulation of claim 4, wherein the buprenorphine is of the free base form, salt form, or mixtures thereof.”
Corresponding claim 4 of ‘827 recites “The biodegradable formulation of claim 3, wherein the drug is buprenorphine, a free base form thereof, a salt form thereof, or mixtures thereof.”
Claim 6 recites “The biodegradable formulation of claim 1, that comprises about 20 to 60% by weight of biodegradable polymer.”
Corresponding claim 5 of ‘827 recites “The biodegradable formulation of claim 2, wherein the formulation comprises about 20% to about 60% by weight of the biodegradable polymer.”
Claim 8 recites “The biodegradable formulation of claim 1, wherein the biodegradable polymer is at least one selected from the group consisting of poly(lactide-co-glycolide), Poly(D,L-lactide), Poly(ε-caprolactone), Polyhydroxybutyrate, Polyanhydrides, Polyorthoesters, and any combination of any of these.”
Corresponding claim 6 of ‘827 recites “The biodegradable formulation of claim 5, wherein the biodegradable polymer is poly(lactide-co-glycolide), poly(D,L-lactide), poly(ε-caprolactone), polyhydroxybutyrate, polyanhydrides, polyorthoesters, or combinations of any of these.”
Claim 9 recites “The biodegradable formulation of claim 1, that provides sustained release of drug for about 90 days or longer.”
Corresponding claim 8 of ‘827 recites “The biodegradable formulation of claim 1, wherein the formulation provides sustained release of the drug for about 90 days or longer.”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/TIGABU KASSA/Primary Examiner, Art Unit 1619