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
To summarize the current election, the applicant elected Group II and the species where the opioid antagonist is naltrexone and the organic acid is anisic acid, without traverse.
Claims 1-4, 6-8, 10-16, 19, and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Claim Objections
Claim 17 is objected to because of the following informalities: the claim recites “a pH of the formulation when hydrated in its environment use”. This phrase is rather awkward and appears to be missing a word or words. The addition of the word “of” before the word “use”, movement of the word “use” in front of the word “environment”, or something similar would improve the recitation. 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.
Claims 17-18, 20-22, 25-27, and 29 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.
Claim 17 recites “a release rate which provides a therapeutic dose of the agent for the period”. There is no treatment recited as the intended use of the device. The agent is an opioid antagonist and such compounds can have a variety of uses to which are attached different ranges of doses, quantitatively and temporally, that are therapeutic. It is unclear what structural or functional constraint is required by the recitation, given that the therapeutic dosing requirements can vary and no particular treatment is sought. For the sake of application of prior art, any release rate will be deemed sufficient to meet the claim limitations. Clarification is still required.
Claim 17 recites “an organic acid that maintains a pH of the formulation when hydrated in its environment use of less than or equal to 11.5 for the delivery period; wherein the formulation is hydrated by a physiological buffer, isotonic saline, phosphate buffered saline, or aqueous propylene glycol or in situ upon subcutaneous implantation of the device”. Depending on the location of the device, its ability to maintain a particular pH will change. Although the product is recited as an “subcutaneously implantable device”, this recitation does not limit the locations where the device can exist. Thus the ability of the device to maintain a pH of the formulation within the claimed range when placed in a pH 6 environment is quite different than if that same device is place in a pH 13 environment. In addition, the location of the device in an acidic environment (e.g., intragastric implantation locale) does not clearly require an acid to be present in order to maintain pH at less than or equal to 11.5. This limitation at issue is both conditional and functional, in light of the amendment, now stating one condition wherein the formulation is hydrated by one of four aqueous liquids. It is not clear how such a composition that is already hydrated can be hydrated again “in its environment use”. As a result, it is unclear whether pH maintenance is actually required when the formulation is provided in hydrated form. Thus the limitations of the claim are unclear.
Claim 22 recites “the formulation when hydrated has an aqueous phase with a pH value between about 3.0-11.5”. The claims do not state the identity of the fluid by which it is hydrated. The requirements of the device change depending on the nature of the hydrating fluid. Thus a single device could produce a pH in the claimed range when in an aqueous fluid with pH 6, but fail to do so when in an aqueous fluid with pH 13.
Claims that are rejected, but are not explicitly expounded upon, are also indefinite because they depend from an indefinite claim and do not add clarity.
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.
Claims 17-18, 21-22, 25-27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Watkins (previously cited) in view of Saxena (previously cited) and the Vivitrol™ reference (previously cited).
Watkins teaches an implantable, potentially subcutaneous, device for delivering a small molecule therapeutic agent that is present as a formulation in combination with an organic acid to improve its solubility (see abstract and paragraphs 8, 58, and 84). The small molecule therapeutic agent may have a solubility in water of less than 1 g/L, a molecular weight of less than 1000 Daltons, and/or include tertiary amines (see paragraph 8, 88 and 90). Sustained release of the small molecule is envisioned to occur over two weeks to six months (see paragraph 85; instant claim 17). Watkins further teaches that the device has an amount of the small molecule therapeutic agent sufficient to provide a therapeutic effect for a period of at least about 30 days, (ii) an organic acid that maintains a pH of the formulation when hydrated in its environment use of between 3.0-6.5 for the delivery period, and (iii) a release rate which provides a therapeutic dose of the agent for the period (see claim 65; instant claims 17, 22, and 27-28). The device includes a porous membrane (partition) in communication with a reservoir (see paragraph 117 and figures 1C-1K). An example details an outer reservoir diameter of 5.21 mm and a length of 41.4 (see example 4; instant claim 21). Further, the formulation is a dry form envisioned as a powder, tablet, or film and does not require metal salts (see paragraph 47 and claims 67-68; instant claims 25-26). Watkins shows various ratios of organic acid to small molecule, including 1:1, where increases in the molar proportion of organic acid yield an increase in the rate of release of the small molecule, thereby making the molar ratio of the two ingredients a result effective variable (see paragraph 121 and figure 2; instant claim 17). Watkins goes on to name anisic acid as a envisioned organic acid (see table 1 and claims 1, 55-56, and 61; instant claims 17 and 29). Naltrexone is not explicitly taught as the small molecule therapeutic agent.
Saxena et al. teach of the desire to deliver naltrexone from an subcutaneous implant to provide sustained release and note the deleterious impact of known tablet implants that employ metal salts (see paragraph 1 and 10, and 82).
The Vivitrol™ reference details that naltrexone has a molecular weight of 341.41, contains a tertiary amine, and is insoluble in water (see page 1 second paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select naltrexone as the small molecule therapeutic agent in the devices of Watkins and anisic acid as their organic acid. The latter choice would have been obvious because Watkins suggests its selection. The choice of naltrexone would have been obvious in light of Saxena and the Vivitrol™ reference who detail the desire to deliver it form a subcutaneous implant over a sustained period and its qualification as a small molecule therapeutic agent in several of the intended categories of Watkins. The selection of a claimed molar ratio of organic acid to opioid antagonist would have been obvious during the course of routine experimentation to optimize the device because it is a result effective variable. Therefore claims 17-18, 21-22, 25-27, and 29 are obvious over Watkins in view of Saxena et al. and the Vivitrol™ reference.
Claims 17-18, 20-22, 25-27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Watkins in view of Saxena et al. and the Vivitrol™ reference as applied to claims 17-18, 21-22, 25-27, and 29 above, and further in view of Martin et al. (previously cited).
Watkins in view of Saxena et al. and the Vivitrol™ reference render obvious the limitations of instant claims 17-18, 21-22, and 25-29. The device taught by Watkins is shown below and contains a porous partition in contact with a cylindrical reservoir to permit hydration of the contained formulation (see figured 1A-1K).
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Elements 2 and 5 are the porous partition and reservoir, respectively (see paragraph 6). The degree of porosity of the partition and its diameter are not explicitly discussed.
Martin et al. teach a subcutaneous implant structured very similarly to that of Watkins, as shown below
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(see paragraphs 19-22 and 49 and figure 3A-3B). The device is structured to provide sustained release of a therapeutic amount of the contained drug into an environment of use for at least 30 days and has a porous partition in communication with a reservoir from which solubilized drug is released (paragraphs 19-22 and 49 and figure 3A-3B). The reservoir and porous partition correspond to components 60 and 76, respectively (see paragraphs 65 and 68). The porous partitions are exemplified with diameters of 3 and 3.5 mm which correspond to a surface area of about 3.14 mm2 (see example 5). Further, Martin et al. detail the porosity of such a partition contributes to the control of the release rate in a direct manner and exemplify it as 50% (see paragraphs 53-60 and 122). This parameter is therefore a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the surface area/diameter and porosity of the porous partition in the device of Watkins in view of Saxena et al. and the Vivitrol™ reference in light of the teachings of Martin et al. who teach a similarly configured device. These modifications would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g. generic partition vs specific partition). Particular selections of porosity as claimed would have been obvious to obtain via optimization as a matter of routine experimentation, given that it is a result effective variable. Therefore claims 17-18, 20-22, 25-27, and 29 are obvious over Watkins in view of Saxena et al., the Vivitrol™ reference, and Martin et al.
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.
The following is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 17-18, 21-22, 25-27, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 (reference application) in view of Watkins and Vivitrol™ reference.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim a subcutaneous implantable device that contains a solid opioid antagonist formulation that releases a therapeutically effective amount of the opioid antagonist for a duration that meets the limitation of at least about 30 days. The devices have a reservoir and a porous partition in communication with the opioid antagonist formulation. The solid opioid antagonist formulation hydrates in a subcutaneous environment and may be a tablet, pellet, or rod. Naltrexone is recited as the opioid antagonist of the copending claims. An organic acid is not recited in the solid opioid antagonist formulation.
Watkins teaches an implantable, potentially subcutaneous, device for delivering a small molecule therapeutic agent that is present as a formulation in combination with an organic acid to improve its solubility (see abstract and paragraphs 8, 58, and 84). The small molecule therapeutic agent may have a solubility in water of less than 1 g/L, a molecular weight of less than 1000 Daltons, and/or include tertiary amines (see paragraph 8, 88 and 90). Sustained release of the small molecule is envisioned to occur over two weeks to six months (see paragraph 85). Watkins further teaches that the device has an amount of the small molecule therapeutic agent sufficient to provide a therapeutic effect for a period of at least about 30 days, (ii) an organic acid that maintains a pH of the formulation when hydrated in its environment use of between 3.0-6.5 for the delivery period, and (iii) a release rate which provides a therapeutic dose of the agent for the period (see claim 65). The device includes a porous membrane (partition) in communication with a reservoir (see paragraph 117 and figures 1C-1K). An example details an outer reservoir diameter of 5.21 mm and a length of 41.4 (see example 4). Further, the formulation is a dry form envisioned as a powder, tablet, or film (see paragraph 47 and claims 67-68). Watkins shows various ratios of organic acid to small molecule, including 1:1, where increases in the molar proportion of organic acid yield an increase in the rate of release of the small molecule, thereby making the molar ratio of the two ingredients a result effective variable (see paragraph 121 and figure 2). Watkins goes on to name anisic acid as a envisioned organic acid (see table 1 and claims 1, 55-56, and 61).
The Vivitrol™ reference details that naltrexone has a molecular weight of 341.41, contains a tertiary amine, and is insoluble in water (see page 1 second paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add anisic acid to the solid naltrexone formulation of the copending claims in lit of Watkins and the Vivitrol™ reference. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement (e.g., improved solubility and sustained release from same/similar device). Naltrexone qualifies as a drug in the genus of compounds envisioned by Watkins in light of the Vivitrol™ reference. The selection of a claimed molar ratio of organic acid to opioid antagonist would have been obvious during the course of routine experimentation to optimize the device because it is a result effective variable. In addition, the application of device dimensions and design of Watkins would follow. Therefore claims 17-18, 21-22, 25-27, and 29 are obvious over claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 in view of Watkins and Vivitrol™ reference.
Claims 17-18, 20-22, 25-27, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 in view of Watkins and the Vivitrol™ reference as applied to claims 17-18, 21-22, 25-27, and 29 above, and further in view of Martin et al.
Claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 in view of Watkins and the Vivitrol™ reference render obvious the limitations of instant claims 17-18, 21-22, and 25-29. The device taught by Watkins is shown below and contains a porous partition in contact with a cylindrical reservoir to permit hydration of the contained formulation (see figured 1A-1K).
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Elements 2 and 5 are the porous partition and reservoir, respectively (see paragraph 6). The degree of porosity of the partition and its diameter are not explicitly discussed.
Martin et al. teach a subcutaneous implant structured very similarly to that of Watkins, as shown below
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(see paragraphs 19-22 and 49 and figure 3A-3B). The device is structured to provide sustained release of a therapeutic amount of the contained drug into an environment of use for at least 30 days and has a porous partition in communication with a reservoir from which solubilized drug is released (paragraphs 19-22 and 49 and figure 3A-3B). The reservoir and porous partition correspond to components 60 and 76, respectively (see paragraphs 65 and 68). The porous partitions are exemplified with diameters of 3 and 3.5 mm which correspond to a surface area of about 3.14 mm2 (see example 5). Further, Martin et al. detail the porosity of such a partition contributes to the control of the release rate in a direct manner and exemplify it as 50% (see paragraphs 53-60 and 122). This parameter is therefore a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the surface area/diameter and porosity of the porous partition in the device of claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 in view of Watkins et al. and the Vivitrol™ reference in light of the teachings of Martin et al. who teach a similarly configured device. These modifications would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g. generic partition vs specific partition). Particular selections of porosity as claimed would have been obvious to obtain via optimization as a matter of routine experimentation, given that it is a result effective variable. Therefore claims 17-18, 20-22, 25-27, and 29 are obvious over claims 1, 5-8, 10-11, 21, 26, 7, 10-11, 29, 33, and 39-41 of copending Application No. 18/840456 in view of Watkins et al., the Vivitrol™ reference, and Martin et al.
Response to Arguments
Applicant's arguments filed August 8, 2025 have been fully considered but they are not persuasive.
The applicant does not address the rejections under 35 USC 112(b) in the remarks.
The applicant argues that the artisan of ordinary skill would not look to Saxena to modify the teachings of Watkins because Saxena teaches directly implanted tablets. To the contrary, the artisan would look to any reference that teaches a drug which fulfills the requirements set forth by Watkins for selecting a drug to include and preferably a drug for which subcutaneous sustained delivery is desired. Naltrexone meets both these requirements. In addition, Saxena discusses several drawbacks of prior attempts to formulate naltrexone as a sustained release implant and the device of Watkins also overcomes these issues (e.g., irritation due to magnesium stearate excipient). Moreover, Watkins provides sustained controlled release that can be tuned to a desired rate based on the companion acid, its proportion, and the accessible membrane proportion. Thus Watkins provides several reasons why the artisan of ordinary skill would seek out additional specific drugs that qualify for inclusion in their device and apply its benefits.
The applicant additionally argues about nuances of the functionality of the implant configuration of Saxena. This argument appears to suggest that these details preclude the utility of naltrexone as a drug in the device of Watkins. However, the teachings of Saxena already establish several approaches to providing naltrexone for sustained release, thus their avenue is not the sole route to an implantable naltrexone deice. Additionally, the selection of naltrexone as a particular drug within the genus taught by Watkins does not require the incorporation of the excipients employed in other sustained release formulations of naltrexone. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
The applicant further argues that there is no guidance for one to include naltrexone in the device of Watkins. To the contrary, Watkins provides multiple examples and discussion of how to make the drug formulation loaded into their device. The applicant has not pointed to any aspect of these teachings that are incompatible with naltrexone or that suggests it could not be treated similarly (e.g., compounded with acid in a common solvent and dried, tableted with acid and lactose binder, etc. - see examples and paragraph 115).
Conclusion
No claim is 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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARALYNNE E HELM whose telephone number is (571)270-3506. The examiner can normally be reached Mon-Fri 9-5.
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/CARALYNNE E HELM/Examiner, Art Unit 1615
/MELISSA S MERCIER/Primary Examiner, Art Unit 1615