DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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.
Specification
The disclosure is objected to because of the following informalities: a trade name or a mark used in commerce in present in the specification and is not properly formatter.
The use of the term PLURONIC®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 2 is objected to because of the following informalities: the phrase “has a” is duplicated in line 2 and one occurrence should be removed. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Indefiniteness
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.
Claims 1 – 7 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 claims states that “one of the PLGAs has an ester end group and the other an acid end group”. An ‘unmodified’ linear PLGA polymer has an alcohol group at one end and a carboxylic acid group as the other polymer end group. Therefore it is not clear if the requirement for a polymer with an acid end group is met by such a unmodified PLGA polymer and if that acid end group is altered to an ester in the second PLGA polymer? Or is the alcohol group modified to either an acid end group in one or an ester group, and both having the other termini being a carboxylic acid? The dependent claims fall therewith. Please clarify.
Claim 2 is 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 claim concludes with “a particle size of 0.1 microns to 15 microns (99 % > 0.1 microns, 99 % < 15 microns)” and what is present in parentheses does not have the exact same scope as the limitation immediately preceding the parentheses. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Please clarify.
Claim 7 is 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. Claim 7 includes the “%” symbol in parenthesis immediately after dL/g leading to the question of if the two are exact synonyms oof each other, what the % is referring to and/or potentially that a broad and narrow recitation is present in the same claim. Please clarify.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1 – 7 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Petersen et al. (WO 2007/071395 on IDS).
Petersen et al. discloses sustained release formulations of octreotide or a pharmaceutically acceptable salt thereof and two or more different polylactide-co-glycolide (PLGA) polymers (whole document, e.g., abstract). Surprisingly, the use of a combination of 2 or more different PLGAs in the composition significantly reduced the fluctuations in plasma levels of the octreotide (p 2, last ¶). The preferred pharmaceutically acceptable salt to prepare the depot formulation is the pamoate monosalt (p 1, last ¶). An amorphous powder of the octreotide is also preferred (p 2, ¶ 1) and the drug substance content of the depot formulation is most preferably between 15% and 20% (p 3, ¶ 6). As the particle size distribution of the drug substance influences the release profile, an amorphous powder which has a particle of a size of about 0.1 microns to about 15 microns (99% > 0.1 microns, 99% < 15 microns) is preferred (p 2, ¶ 1). The PLGA can have a lactide:glycolide monomer ratio that varies (p 3, ¶ 1), but is not required, with inherently viscosities that are at least below 0.9 dl/g in chloroform (p 3, ¶ 4). Exemplary end groups for the PLGA include both carboxyl and ester groups (p 3, ¶ 5). Table 1 shows suitable polymers, including those with a free carboxylic acid end group (No 2) and PLGA with ester end groups were used in the example (see p 14). The microparticles most preferably have a diameter of 10 – 90 microns (p 7, ¶ 1). The diameter of the produced particles was measured and the X90 value (90% of all particles are smaller than this value) is reported in table 2 (p 11, ¶ 3). The X90 values varied but fell within the preferred range (see table 2). The particles themselves can also be mixed or coated with an anti-agglomerating agent or covered by a layer of anti-agglomerating agent (p 7, ¶ 2).
Petersen et al. does not specifically prepare an octreotide depot formulation with a blend of two different PLGAs having a 75:25 L:G ratio, different viscosities and one with an ester end group and one with a carboxylic acid end group.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to use PLGA polymers with a 75:25 L:G ratio and different end groups to prepare an octreotide depot formulation using amorphous form of octreotide such as the pamoate monosalt. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Petersen et al. discloses that PLGA polymers of varying monomer ratios and end groups can be used to prepare microparticles of various sizes loaded with octreotide or a salt such as the pamoate salt. Factors such as the particle size and drug loading are results effective parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount, type and size (physical size and molecular weight) of each ingredient to add in order to best achieve the desired results based on the desired overall release profile, drug concentration and time frame of drug release. Parameters such as the L:G ratio and viscosity overlap with the presently claimed ranges and such ranges are prima facie obvious (see MPEP 2144.05) and there is no evidence of record as to the criticality of the claimed values.
Claims 1 – 7 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Petersen et al. as applied to claims 1 - 7 above, and further in view of Chen et al. (WO 2004/043432 on IDS).
Petersen et al. is discussed above.
Explicit motivation to alter the end groups of the PLGA polymer is not disclosed.
Chen et al. discloses depot gel compositions injected into a desired location for controlled release of a beneficial agent (¶ [0001]), including octreotide (¶ [0145]). Polymers such as PLGA copolymers with various L:G ratios can be used to prepare the viscous gel (¶ [0012]). Release rates of the beneficial agent can be varied by varying the polymer properties – including the type of polymer, the molecular weight of the polymer, the end group of the polymers and the co-monomer ratio of the polymer, among others (¶ [0091] onward). Gels prepared with a 50:50 L:G ratio has a relatively short duration of delivery (2 days – 1 month) while a polymer with 65:35 L:G ratio has a delivery duration of about 2 months (¶ [0096]) and one with a 75:25 ratio provided sustained release over a period of approximately 3 – 4 months (¶ [0092]). A mixture of the polymer PLGA RG502H having an acid end group with PLGA RG502 having an ester end group results in a depot formulation with a lower burst index than a PLGA RG502 only formulation (¶ [0098]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to use PLGA polymers with a 75:25 L:G ratio and different end groups to prepare an octreotide depot formulation using amorphous form of octreotide such as the pamoate monosalt. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because as discussed by Chen et al., the co-monomer ratio (L:G ratio), the inherent viscosity of the PLGA polymers and the types of end groups on the polymers effect the degradation rate of the material and the release rate of the active ingredient (octreotide) and Petersen et al. discloses that blends of PLGA polymers can reduce the fluctuations in plasma levels of the drug when administered. Thus, the use of PLGA polymers with different end groups will provide additional flexibility in obtaining the desired release profile. Factors such as the particle size and drug loading are results effective parameters that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount, type and size (physical size and molecular weight) of each ingredient to add in order to best achieve the desired results based on the desired overall release profile, drug concentration and time frame of drug release. Parameters such as the L:G ratio and viscosity overlap with the presently claimed ranges and such ranges are prima facie obvious (see MPEP 2144.05) and there is no evidence of record as to the criticality of the claimed values.
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, 3, 4, 6 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 19 of copending Application No. 18/956,119 in view of Chen et al. (WO 2004/043432).
The claims of US’119 recite a sustained release pharmaceutical composition in form of microparticles having an active ingredient octreotide, such as the pamoate salt (claim 9) and two different PLGAs as a polymer blend wherein the lactide: glycolide (L:G) ratios of the different PLGAs are different from each other (claim 1). The L:G ratios are 85:15 to 65:3 (claim 5) with viscosities below 0.9 dl/g or 0.8 dl/g (claims 6 and 7). The PLGAs can be linear (claim 8). The PLGA microparticles can be coated with an anti-agglomerating agent (claim 11). A process for manufacturing such a product is also claimed (claims 15 – 17).
The use of PLGAs with acid and ester end groups is not claimed.
Chen is discussed above.
It would have been obvious to the person of ordinary skill in the art before the date of invention to incorporate the PLGA end group chemistry of Chen into drug depot. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because PLGA blends where one polymer has an ester end group and the other has an acid end group have been shown in the art to lower the initial burst of active ingredient leaving more drug to be released over time.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 - 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 19 of copending Application No. 18/956,119 in view of Chen et al. (WO 2004/043432) and Petersen et al. (WO 2007/071395).
The claims of US’119 and Chen are discussed above.
The PLGA and octreotide pamoate particle sizes are not claimed.
Petersen et al. and Chen et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the date of invention to use octreotide pamoate particle sizes and overall particle sizes from Petersen et al. and into the drug depot of US’119 and Chen et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because PLGA and octreotide particle sizes have been shown in the art to provide release of drug over three months and such information is not provided by the claims of US’119.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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