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 .
Applicant’s arguments, filed 07/06/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 33-52 are pending.
Claims 41-45, 51, and 52, are withdrawn.
Specification
The abstract of the disclosure is objected to because “and” is missing following “hydrogel particle,” and “a carrier medium”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112(b) or pre-AIA 2nd ¶
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 33-40 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 33 newly recites “solid hydrogel particles comprising reactive hydrogel precursors in a solid state” and further recites that upon injection, a hydrogel forms. It is unclear if the solid hydrogel particles are pre-formed hydrogels that are loaded with solid hydrogel precursors that are later reacted at the interface to form an additional hydrogel at the particle interface, or if Applicants are attempting to define the solid hydrogel precursors as solid hydrogel particles based on what they are later to become upon dissolution and in situ crosslinking. If the latter, it is unclear how they would be considered hydrogels if they are unreacted hydrogel precursors that have not yet formed into hydrogels. From the instant specification, paragraph 18 recites the solid hydrogel particles may consist of dehydrated cross-linked particles OR reactive precursors, and there appears to be no recitations of pre-formed hydrogel particles loaded or otherwise combined with unreacted solid hydrogel precursors into a single particle. For purposes of examination, the Examiner best understands the “solid hydrogel particles” to be the solid particles of reactive hydrogel precursors, that later form the hydrogels.
Claims 34-40 are rejected for the same reasons for depending upon rejected claim 33.
Claim Rejections - 35 USC § 112(d) or pre-AIA 4th ¶
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 34 and 35 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 34 recites wherein the solid hydrogel particles contain reactive precursors, which fails to limit claim 33 which recites solid hydrogel particles comprising reactive hydrogel precursors in solid form.
Claim 35 is rejected for the same reasons for depending upon claim 34.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 33-40, and 46-49, are rejected under 35 U.S.C. 103 as being unpatentable over Campbell et al (US 20110142936 A1, hereinafter “Campbell”), in view of Bright et al (US 20200085809 A1, hereinafter “Bright”) and Rizzi et al (US 20150247119 A1, hereinafter “Rizzi”).
Campbell teaches a pharmaceutically acceptable implant system comprising hydrogel particles that are suspended in a liquid and applied to a site (abs, ¶¶ 103, 128, 159, claim 1). In other embodiments, the implant involves delivering precursors to a site, where the precursors react with each other and form an in-situ hydrogel (¶¶ 5, 128). The therapeutic agent may be mixed with the precursors (¶¶ 94, 128). Precursors and hydrogel particles may also be mixed and injected to a site (¶ 128). The precursors may be dissolved in, or suspended in, a liquid and applied to the site (¶ 103). The particles may be created and then broken up by grinding, etc. (¶ 109). The hydrogel may comprise therapeutic agents that are released over a period of time, where rate of release from the hydrogel will depend on the properties of the drug and the hydrogel, with factors including drug sizes, relative hydrophobicities, hydrogel density, hydrogel solids content, and the presence of other drug delivery motifs, e.g., microparticles. (¶¶ 66, 92). The hydrogel precursor may be used to deliver different classes of drugs including local anesthetics, etc. (¶ 93). The particles may be fully hydrated, partially hydrated, or desiccated (¶ 129). The particle solvent may be water, with salts or buffers being present as desired (¶ 134). The particles may be spheroidal and range from about 10 to about 500 microns (¶¶ 110, 116). The hydrogel particles may be formulated via a variety of methods (¶ 111). Hydrogels are materials that do not dissolve in water and retain a significant fraction (more than 20%) of water within their structure (¶ 28). The system is suitable for injection (¶ 134).
Campbell does not specifically disclose wherein the hydrogel precursors are in a solid state.
Bright teaches hydrogel formulations for local neuromodulation and delivery of a therapeutic agent to a target site, where it was known to inject dehydrated hydrogel precursors mixed with drug molecules for in-situ hydrogel formation (abs, ¶¶ 121, 191, 309). In one embodiment, the precursors may comprise a lyophilized, or freeze-dried forms that are compounded together with the drug (¶ 309). Upon exposure to an aqueous environment, including water in bodily tissues, rapid chemical crosslinking occurs and forms a drug-releasing hydrogel implant (¶ 309). The crosslinking may be covalent (¶¶ 211, 235). The drug may be loaded between 10 and 80% for sustained release over a period of hours to months (¶ 185).
Additional motivation is provided by Rizzi, where Rizzi teaches particulate hydrogel precursor formulations where it was known to mix solutions of precursor and bioactive agent, followed by lyophilization into particulate form (abs, ¶¶ 10, 45). The powder may comprise particles having any size and shape (¶ 10). The formulation has the advantage that the powder may simply be re-suspended to start the gelling reaction, and no mixing of different components is required, thus considerably reducing the probability of erroneous ratios between the at least one structural compound and the at least one linker compound (¶ 9). Thus, this increases the reproducibility of the hydrogels produced from these hydrogel precursors, and provides ease of use (¶ 9).
Regarding claim 33, where Campbell teaches in situ forming hydrogel formulations, and teaches systems comprising hydrogel particles, precursors, and mixtures thereof, it would have been obvious to modify the implant system of Campbell by formulating the precursors in other known forms suitable for in situ hydrogel formation, such as solid hydrogel particles comprising hydrogel precursor particles, as taught by Bright, depending on desired formulation type, and where Campbell and Bright are both directed to in situ hydrogel formulations for delivery of a neuromodulatory drug comprising administering hydrogel particles/precursors to a target site. Further, it would have been obvious to include a liquid carrier medium, as taught by Campbell, such as for injection. Additional motivation for solid precursor particles is provided by Rizzi, where solid hydrogel precursors combined with active agent were known to result in hydrogel precursor particles that are easy to use, do not require different components, increase reproducibility, etc.
Regarding the neuromodulatory agent, it would have been obvious to formulate the implant system comprising an anesthetic agent (i.e., a neuromodulatory agent) for sustained release, and where Bright teaches neuromodulating agents are suitable for in situ forming hydrogel comprising solid precursor particles, depending on the desired treatments..
Regarding the limitation of in situ formation of a singular depot for sustained release of the agent, the limitation appears to be the intended use of the implant system, requiring the step of injection. Accordingly, where the system made obvious above comprises solid hydrogel precursor particles, a neuromodulatory agent, and a carrier medium, appearing to meet the claimed limitations, it appears the system would be capable of in situ formation of a singular depot for controlled release of the agent upon injection. Purely arguendo, even if not, it would have been obvious to formulate the system made obvious that is capable of in situ formation of a singular depot for sustained release, where in situ implants for sustained release of actives are taught by Campbell and Bright.
Regarding the limitations tied to injection, the limitation is simply the intended use of the system made obvious above, and where the system made obvious above is taught to be capable of being injected, the intended use limitation is met.
Regarding the functional limitations, the functional limitations are tied to the intended use limitation of injection, which is met for the reasons discussed above, nevertheless, where the Cambell and Bright teach the precursors crosslink to form a hydrogel implant, the function of the precursor particles when exposed to aqueous in tissues would be reasonably expected to be the same, i.e., undergo interfacial dissolution and in situ crosslinking to form a hydrogel at the particle interfaces, where the particle interfaces would be exposed to aqueous. Further, where the particles are taught to form a hydrogel implant, and where the precursors are taught to crosslink upon exposure to dissolution media, it appears that a single localized aggregate would form, and the hydrogel formed would be reasonably expected to deter the migration and provide sustained release of the neuromodulatory agent, as instantly claimed, where Campbell and Bright teach in situ hydrogels for sustained release.
Regarding claim 34, the limitation does not appear to further limit claim 33 for the same reasons discussed above and where solid hydrogel precursor particles are made obvious above, the limitation appears to be met.
Regarding claim 35, it would have been obvious to select precursors that covalently crosslink, as taught by Campbell and Bright.
Regarding claims 36 and 37, where Campbell teaches the particles may be spheroidal and range from about 10 to about 500 microns, were Bright makes obvious solid hydrogel precursors, and Rizzi teaches solid hydrogel precursors can be formulated in any size, it would have been obvious to formulate the solid hydrogel particles within sizes that were known to be suitable for in situ depot formation for sustained release of a neuromodulator agent via injection, such as from about 10 to about 500 microns, as taught by Campbell, overlapping the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Further, where these particle sizes were known to be suitable for injectable in-situ hydrogel formation, it would have been well within the relative skills of the skilled artisan to have routinely optimized the particle sizes for desired administration, needle size, implant site, 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. Where 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. See MPEP 2144.05(II)(A).
Regarding claim 38, it would have been obvious to select from an anesthetic (i.e., neuromodulating agent) as the active agent, as taught by Campbell, and where Bright teaches neuromodulating agents are suitable for in situ forming hydrogel comprising solid precursor particles, depending on the desired treatments.
Regarding claim 39, it would have been obvious to further include an additional therapeutic agent, where Campbell teaches a therapeutic agent, or agents, may be included, in order to formulate a system with desired therapeutic activity.
Regarding claim 40, where the claims are directed to an implant system, the limitation of wherein the neuromodulatory agent is released in a sustained manner due to delayed diffusion of water is tied to the intended use of the implant system, which would require the step of administering the implant system to form the depot for sustained release. Accordingly, where the implant system as instantly claimed is made obvious above and comprises the same components, and are suitable for forming a sustained release hydrogel depot, it appears the system would be capable of releasing the neuromodulatory agent in a sustained release manner by delayed diffusion of water into the depot for sustained release.
Regarding claim 46, it would have been obvious to formulate an implant system comprising a neuromodulating agent and solid hydrogel precursor particles in a carrier for the same reasons discussed above by Campbell, Bright, and Rizzi.
Regarding wherein the plurality of particles comprise a neuromodulating agent, it would have been obvious to formulate the plurality of solid particles comprising solid hydrogel precursor particles and the neuromodulatory agent, where particles comprising reactive precursors and active agent were known from Rizzi, and where Rizzi teaches where mixing hydrogel precursors and active agent prior to lyophilizing into particles was known to result in hydrogel precursor particles that are easy to use, do not require different components, increase reproducibility, etc.
Regarding the intended use and functional limitations, the limitations appear to be met for the same reasons discussed above.
Regarding claim 47, where Bright teaches systems comprising solid hydrogel particles and dehydrated hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer), and teaches the drug loading levels can be from about 1 to 80% in the formulations, it would have been obvious to modify the system made obvious above by including known amounts of neuromodulatory agents suitable for systems comprising solid hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer) for sustained release of the active, such as from about 1 to about 80% within the plurality of solid particles. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, it would have been well within the relative skills of the skilled artisan to routinely adjust the amount of the active ingredient for various release profiles, therapeutic activity, the particular active agent, 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. Where 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. See MPEP 2144.05(II)(A) and (B).
Regarding claim 48, where the claims are directed to an implant system, the limitation of wherein the neuromodulatory agent is released in a sustained manner due to delayed diffusion of water is tied to the intended use of the implant system, would require the intended use step of administering the implant system to form the depot for sustained release. Accordingly, where the implant system as instantly claimed is made obvious above and comprises the same components, and are suitable for forming a sustained release hydrogel depot, it appears the system would be capable of releasing the neuromodulatory agent in a sustained release manner by delayed diffusion of water into the depot for sustained release.
Regarding claim 49, it would have been obvious to select from water soluble drugs, such as those with high water solubility, where these agents were known to be suitable for sustained release by Campbell, depending on desired release profiles from the resulting depots, and were Campbell teaches the rate of release from the hydrogel will depend on the properties of the drug, etc.
Further, where the claims are directed to an injectable neuromodulating system, the limitation of release >24 hours is tied to the intended use of the injectable system, which would require the step of administering the system to form the hydrogel depot capable of sustained release. Accordingly, where the system made obvious above comprises the same components as instantly claimed, are capable of sustained release of an active agent, it appears the system would be capable of forming a hydrogel depot with an active release of > 24 hours.
While it appears that the limitation of sustained release is tied to the intended use of the systems as instantly claimed is made obvious above, purely arguendo, if not, it would have been obvious to formulate a system for sustained release of the neuromodulatory agent from of hours to months, where Bright teaches systems for formulating hydrogel implants for sustained release of neuromodulatory agents can be formulated for of hours to months of sustained release, depending on desired treatments, therapeutic activity, etc.
Response to Arguments
In summary, Applicants assert Campbell does not teach or disclose the newly amended architecture of wherein the solid hydrogel particles comprising reactive hydrogel precursors in solid state, and assets Campbell teaches administering preformed dehydrated hydrogel particles or flowable precursors that react to form the in-situ hydrogel implants. Thus, Applicants assert Campbell does not teach the functional limitations newly amended into claim 33 and 46.
Respectfully, this argument is not persuasive. In view of Applicants’ amendments to the instant claims, Bright and Rizzi are newly cited above to address the claimed limitations and are obvious for the same reasons discussed above. Further, regarding the intended use and subsequent functional limitations that follow the intended use, the limitations appear to be met for the same reasons discussed above. Where the claims are rejected over the new combination of Campbell, Bright, and Rizzi, and Campbell, Bright, Rizzi, and King, Applicants argument with respect to the teachings of Campbell alone are moot at this time.
Claims 46-50 are rejected under 35 U.S.C. 103 as being unpatentable over Campbell et al (US 20110142936 A1, hereinafter “Campbell”), Bright et al (US 20200085809 A1, hereinafter “Bright”), and Rizzi et al (US 20150247119 A1, hereinafter “Rizzi”), and further in view of King et al (US 20060074182 A1), as evidenced by Lanao et al (Tissue Engineering, 2013, vol 19, no. 4, pp-380-390, hereinafter “Lanao”).
Campbell is discussed above and further teaches high water soluble drugs may be loaded within microparticles, e.g., PLGA, including microparticles having a hydrophobic nature, to control the rate of release from the hydrogel (¶¶ 92, 93, 97). As evidenced by Lanao, PLGA is a hydrophobic polymer (pg 383 2nd col 1st ¶).
Campbell, Bright, and Rizzi are discussed above but do not specifically teach wherein each agent is encapsulated in a hydrophobic secondary polymer and dispersed within the reactive hydrogel precursor particles during melt formation and incorporated into the plurality of solid particles upon solidification of the reactive hydrogel precursor particles of claim 50. Further, purely arguendo, if somehow the plurality of particles made obvious above do not read on comprising the agent, and is required to be encapsulated within each hydrogel precursor particle, the following also applies.
King teaches hydrogel compositions formed from precursor particles, wherein the precursor particles are melt-processable, and it was known to mix active ingredient within the molten matrix precursors (¶¶ 13, 28, 30). The precursor may be in the form of powders, etc. (¶ 28).
Regarding claim 46, it would have been obvious to formulate an implant system comprising a neuromodulating agent and solid hydrogel precursor particles in a carrier for the same reasons discussed above by Campbell, Bright, and Rizzi.
Regarding wherein the particles comprise a neuromodulating agent, it would have been obvious to formulate the plurality of solid hydrogel precursor particles comprising the neuromodulatory agent, where it was known from King that hydrogel precursor particles can be melt processed/mixed with hydrogel precursors, wherein the precursors may be in the form of powders. Additional motivation is provided by Rizzi, where mixing hydrogel precursors and active agent prior to lyophilizing into particles was known to result in hydrogel precursor particles that are easy to use, do not require different components, increase reproducibility, etc.
Regarding the intended use and functional limitations, the limitations appear to be met for the same reasons discussed above.
Regarding claim 47, where Bright teaches systems comprising solid hydrogel particles and dehydrated hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer), and teaches the drug loading levels can be from about 1 to 80%, it would have been obvious to modify the system made obvious above by including known amounts of neuromodulatory agents suitable for systems comprising solid hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer) for sustained release of the active, such as from about 1 to about 80% within the plurality of solid particles. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, it would have been well within the relative skills of the skilled artisan to routinely adjust the amount of the active ingredient for various release profiles, therapeutic activity, the particular active agent, 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. Where 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. See MPEP 2144.05(II)(A) and (B).
Regarding claim 48, where the claims are directed to an implant system, the limitation of wherein the neuromodulatory agent is released in a sustained manner due to delayed diffusion of water is tied to the intended use of the implant system, which would require the step of administering the implant system to form the depot for sustained release. Accordingly, where the implant system as instantly claimed is made obvious above and comprises the same components, and are suitable for forming a sustained release hydrogel depot, it appears the system would be capable of releasing the neuromodulatory agent in a sustained release manner by delayed diffusion of water into the depot for sustained release.
Regarding claim 49, it would have been obvious to select from water soluble drugs, such as those with high water solubility, where these agents were known to be suitable for sustained release by Campbell, depending on desired release profiles from the resulting depots, and were Campbell teaches the rate of release from the hydrogel will depend on the properties of the drug, etc.
Further, where the claims are directed to an injectable neuromodulating system, the limitation of release >24 hours is tied to the intended use of the injectable system, which would require the step of administering the system to form the hydrogel depot capable of sustained release. Accordingly, where the system made obvious above comprises the same components as instantly claimed, are capable of sustained release of an active agent, it appears the system would be capable of forming a hydrogel depot with an active release of > 24 hours.
While it appears that the limitation of sustained release that is tied to the intended use of the systems as instantly claimed is made obvious above, purely arguendo, if not, it would have been obvious to formulate a system for sustained release of the neuromodulatory agent from of hours to months, where Bright teaches systems for formulating hydrogel implants for sustained release of neuromodulatory agents can be formulated for of hours to months of sustained release, depending on desired treatments, therapeutic activity, etc.
Regarding claim 50, it would have been obvious to encapsulate the agent made obvious above in a hydrophobic secondary polymer, such as PLGA, as taught by Campbell, in order to achieve a desired release profile for the intended use of the system.
Additionally, the limitation of suspension within precursor melt particles appears to be a product by process limitation, and where solid precursor particles comprising the encapsulated agent is made obvious above, it appears the limitation is met. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. 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. Therefore, the method of formulating precursor particles comprising encapsulated agent does not distinguish the compositions from that of the prior art. Purely arguendo, even if not, where King teaches it was known to formulate hydrogel precursors with active agents as a melt, and wherein the precursors can be solid particles, it would have been obvious to suspend the encapsulated agent within the particles during melt processing.
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 33-40, and 46-50, are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11,154,547 B2, hereinafter referred to as ‘547, in view of Campbell et al (US 20110142936 A1, hereinafter “Campbell”), Venkateswara-Rao et al (WO 2018005848 A1, hereinafter “Venkatestwara-Rao”, cited on IDS dated 12/15/2023), Rizzi et al (US 20150247119 A1, hereinafter “Rizzi”), and King et al (US 20060074182 A1, hereinafter “King”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘547 disclose a method of modulating inflammation in a patient comprising an injectable in situ forming hydrogel slurry.
Campbell, King, and Rizzi are discussed above.
Venkatestwara-Rao teaches hydrogel formulations for local neuromodulation and delivery of a therapeutic agent to a target site, where it was known to inject dehydrated hydrogel precursors mixed with drug molecules for in-situ hydrogel formation (abs, ¶¶ 121, 280). In one embodiment, the precursors may comprise a lyophilized, or freeze-dried forms that are compounded together with the drug (¶ 280). Upon exposure to an aqueous environment, including water in bodily tissues, rapid chemical crosslinking occurs and forms a drug-releasing hydrogel implant (¶ 280). The crosslinking may be covalent (¶¶ 213). The drug may be loaded between 10 and 80% for sustained release over a period of hours to months (¶ 187). Neuromodulating agents that can be used in treatments to reduce inflammation (title, ¶ 192).
The claims of ‘547 do not disclose a neuromodulating agent as instantly claimed, solid particulate hydrogel particles nor their size, sustained release, the loading of the agent, nor wherein the agent is encapsulated in a secondary hydrophobic polymer in precursor melt particles.
It would have been obvious to formulate the injectable in situ formulating hydrogel slurry of ‘547 with solid hydrogel particles comprising solid precursors in a carrier medium, which are taught to be suitable for hydrogel formation by Campbell, Venkatestwara-Rao, and Rizzi, for the same reasons discussed above.
It would have been obvious to include known active agents suitable for injectable hydrogel systems for reducing inflammation, including neuromodulating agents, as taught by Venkatestwara-Rao.
It would have been obvious to include an anesthetic, where anesthetics were known to be suitable for implant systems for reducing inflammation, as taught by Venkatestwara-Rao.
It would have been obvious to formulate the particles with a size ranging from about 10 to about 500 microns, as taught by Campbell, for the same reasons discussed above. Further, where these particle sizes were known to be suitable for injectable in-situ hydrogel formation, it would have been well within the relative skills of the skilled artisan to have routinely optimized the particle sizes for desired administration, needle size, implant site, 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. Where 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. See MPEP 2144.05(II)(A).
Where the claims of ‘547 are directed to administrating an active agent to modulate inflammation, it would have been obvious to formulate a system capable of sustained release of the active agent, in order to provide a therapeutic effect over a prolonged period of time, as taught by Campbell.
Where Venkatestwara-Rao teaches systems comprising solid hydrogel particles and dehydrated hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer), and teaches the drug loading levels can be from about 1 to 80%, it would have been obvious to modify the system made obvious above by including known amounts of neuromodulatory agents suitable for systems comprising solid hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer) for sustained release of the active, such as from about 1 to about 80%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, it would have been well within the relative skills of the skilled artisan to routinely adjust the amount of the active ingredient for various release profiles, therapeutic activity, the particular active agent, 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. Where 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. See MPEP 2144.05(II)(A) and (B).
It would have been obvious to encapsulate the agent in a secondary hydrophobic polymer included in a reactive precursor particle, for the same reasons discussed above by Campbell, Rizzi, and King.
Claims 33-40, and 46-50, are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 12,029,733 B2, hereinafter referred to as ‘733, in view of Campbell et al (US 20110142936 A1, hereinafter “Campbell”), Bright et al (US 20200085809 A1, hereinafter “Bright”), Rizzi et al (US 20150247119 A1, hereinafter “Rizzi”), and King et al (US 20060074182 A1, hereinafter “King”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘733 disclose a method of modulating hypertension comprising an injectable in situ forming hydrogel slurry being for delivering a therapeutic agent.
The claims of ‘733 do not disclose a neuromodulating agent as instantly claimed, solid particulate hydrogel particles nor their size, sustained release, the loading of the agent, nor wherein the agent is encapsulated in a secondary hydrophobic polymer in precursor melt particles.
Bright is discussed above and further teaches neuromodulation may be used to treat hypertension (¶ 47).
Campbell, Bright, Rizzi, and King are discussed above.
It would have been obvious to formulate the injectable in situ formulating hydrogel slurry of ‘733 with solid hydrogel particles comprising solid precursors in a carrier medium, which are taught to be suitable for hydrogel formation by Campbell and Bright, for the same reasons discussed above.
It would have been obvious to include known active agents suitable for injectable hydrogel systems for modulating hypertension, including neuromodulating agents, as taught by Bright.
It would have been obvious to include an anesthetic, where anesthetics were known to be suitable for implant systems, as taught by Bright, depending on the desired therapeutic effect.
It would have been obvious to formulate the particles with a size ranging from about 10 to about 500 microns, as taught by Campbell, for the same reasons discussed above. Further, where these particle sizes were known to be suitable for injectable in-situ hydrogel formation, it would have been well within the relative skills of the skilled artisan to have routinely optimized the particle sizes for desired administration, needle size, implant site, 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. Where 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. See MPEP 2144.05(II)(A).
Where the claims of ‘733 are directed to administrating an active agent to modulate hypertension, it would have been obvious to formulate a system capable of sustained release of the active agent, in order to provide a therapeutic effect over a prolonged period of time, as taught by Campbell.
Where Bright teaches systems comprising solid hydrogel particles and dehydrated hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer), and teaches the drug loading levels can be from about 1 to 80%, it would have been obvious to modify the system made obvious above by including known amounts of neuromodulatory agents suitable for systems comprising solid hydrogel precursors, neuromodulatory agents, and a carrier medium (i.e., the aqueous buffer) for sustained release of the active, such as from about 1 to about 80%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, it would have been well within the relative skills of the skilled artisan to routinely adjust the amount of the active ingredient for various release profiles, therapeutic activity, the particular active agent, 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. Where 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. See MPEP 2144.05(II)(A) and (B).
It would have been obvious to encapsulate the agent in a secondary hydrophobic polymer included in a reactive precursor particle, for the same reasons discussed above by Campbell, Rizzi, and King.
Conclusion
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.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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