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 . Claims 1-4, 6, 9, 11, 17-20, 23-25, 30, 33-34, 54-57, 62-63, 68-73, and 75-79 are pending; claims 30, 62-63, 68-73, and 75-79 are withdrawn, claims 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57 are examined.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-4, 6, 9, 11, 17-20, 23-25, 30, 33-34, 54-57 in the reply filed on 22 January 2026 is acknowledged. The traversal is on the ground that examining Groups I and II simultaneously would not impose an undue burden on the examiner. This is not found persuasive because Group I is directed to a composition and does not require a device or sterilization process as recited in Group II.
The requirement is still deemed proper and is therefore made FINAL.
Claims 62-63, 68-73, and 75-79 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 30 is withdrawn from further consideration as being drawn to a nonelected species.
Claim Objections
Claim 11 is objected to because of the following informalities: immediately after “peptidomimetic” in line 2 there should be recited --- compound ---. Appropriate correction is required.
Claim 24 is objected to because of the following informalities: immediately after “;” of the line reciting Compound III, there should be recited --- and ---. Appropriate correction is required.
Claim 24 is objected to because of the following informalities: “or a pharmaceutically acceptable salt thereof” in the last line should be removed as it is already recited in line 3 of the claim. Appropriate correction is required.
Claim 25 is objected to because of the following informalities: there appears to be two instances of claim 25, one recites limitations (starting on p. 5 of the Claims filed 05/01/2024), and one showing as cancelled (p.6, fourth line from the bottom). It appears the cancelled claim should be renumbered claim 26. Appropriate correction is required.
Claim 25 is objected to because of the following informalities: immediately after “;” of the line reciting Compound III, there should be recited --- and ---. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2-4, 6, 9, 11, 20, and 23-25 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.
Regarding claims 2 and 3, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 4, 6, 9, and 23-25 recite the limitation "the microparticles" in line 1 of claim 25; lines 1-2 of claims 4, 6, and 23; and in line 2 of claims 9 and 24. There is insufficient antecedent basis for this limitation in the claims. Claim 1, from which the claims depend, recites a plurality of microparticles. To obviate this issue, it is suggested for the claims to recite --- the plurality of microparticles ---.
The term “about” in claims 4, 6, 9, 11, and 20 is a relative term which renders the claim indefinite. The term “about” 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. It is not clear what ranges are encompassed by the term “about,” such that one of ordinary skill in the art would know when a value infringes on the claimed invention.
Claim Rejections - 35 USC § 112(d)
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.
Claim 25 is 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 25 recites wherein the microparticles comprise an oligopeptide selected from the group consisting of elamipretide, Compound II, Compound III, Compound IV, and pharmaceutically acceptable salts thereof.
Claim 24, from which claim 25 depends, recites wherein the microparticles comprise an oligopeptide selected from the group consisting of elamipretide, Compound II, Compound III, Compound IV, and pharmaceutically acceptable salts thereof.
Thus claim 25 fails to further limit claim 24.
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
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 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57 are rejected under 35 U.S.C. 103 as being unpatentable over Schiffman et al. (WO 2019/246141 A1, 12/16/219, IDS reference) (hereinafter Schiffman).
Note: for citation purposes, the US equivalent (US 2021/0100907 A1) will be cited in place of WO 2019/246141 A1.
Regarding claims 1, 19, and 33, Schiffman discloses a drug delivery system comprising a mitochondrial peptide or an oligonucleotide (abs) including elamipretide ([0017]), and may include a biodegradable silica based sustained delivery component ([0057], [0058]) such as a shear-thinning, injectable silica hydrogel composite, obtainable by mixing silica particles with a silica sol. Such delivery system is described by U.S. Pat. No. 9,949,922, issued on Apr. 24, 2018 to Jokinen, et al., which is incorporated by reference herein in its entirety, and is an all-silica-based microparticle-silica hydrogel controlled release system which reduces the burst effect ([0059]).
Jokinen et al. (U.S. Pat. No. 9,949,922, Apr. 24, 2018; for citation purposes US 2016/0136088 A1 will be cited in place of US 9,949,922) discloses a silica hydrogel composite obtainable by mixing silica particles, comprising an encapsulated agent, with a silica sol, wherein obtained hydrogel composite is shear-thinning, injectable, flowing or extrudable (abs). Shear-thinning is a rheological property of a composition. Before injection, e.g. as stored in a syringe and/or at temperatures < 37 °C, the composition is a gel. When shear stress is applied on the injectable gel, e.g. by injecting the injectable gel from a syringe through a thin needle (18-25 G), it turns into a flowing form. When the shear stress ends, e.g., after injection with the thin needle, the injectable gel is again a gel, non-flowing ([0036]). The silica hydrogel composite comprises up to 85 wt.% of said silica particles ([0022]), and comprises from 0.1 to 70 wt. % of the encapsulated agent ([0075]). The molecular weight of encapsulated agent of the silica hydrogel composite is ≤ 10,000 ([0084]). The formation of the hydrogel may be controlled by adjusting pH ([0039]). Exemplary final pH ranges include 5.5-5.9 ([0116]).
Accordingly, Schiffman discloses a depot formulation ((abs): drug delivery system; [0058]: sustained release component) comprising a biodegradable silica hydrogel composite ([0057]), wherein the hydrogel composite comprises a silica hydrogel and a plurality of microparticles comprising silica (Jokinen (abs): silica hydrogel composite obtained by mixing silica particles with a silica sol) and an oligopeptide or a peptidomimetic compound ([0017]: elamipretide); wherein the hydrogel composite is non-flowing and structurally stable when stored at rest, and shear-thinning when shear stress is applied (Jokinen (abs): hydrogel composite is shear-thinning; [0036]: is a gel when stored at temp < 37 °C. When shear stress is applied, it turns into a flowing form. When the shear stress ends, it is again a gel, non-flowing). Together these would provide a depot formulation as instantly claimed.
The prior art is not anticipatory insofar as this combination must be selected from various lists/locations in the reference. It would have been obvious, however, to make the combination since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See MPEP § 2143 (I)(A).
Regarding the claim reciting wherein a freebase equivalent of the oligopeptide or the peptidomimetic compound has a molecular weight less than 1200 amu, Schiffman discloses wherein the mitochondrial peptide or oligonucleotide includes elamipretide. As noted by pp. 7-8 of the instant Specification, elamipretide is an oligopeptide. As noted by p. 15 of the instant Specification, freebase equivalent refers to a compound in its simplest, lowest molecular weight form, not including salts or other atoms, molecules or agents that might typically be associated with, or complexed to, the compound. Accordingly, one of ordinary skill in the art would reasonably conclude the elamipretide of Schiffman to possess substantially the same properties as the claimed invention, such as a molecular weight less than 1200 amu.
Regarding claims 2 and 3 reciting wherein the oligopeptide or the peptidomimetic compound is positively charged in aqueous buffered solution at neutral pH, or is water soluble, Schiffman discloses the same compound (i.e. elamipretide). As noted by p. 15 of the instant Specification, elamipretide comprise three basic nitrogen atoms that typically will complex a negative ion when the nitrogen is protonated (and thereby rendered positive in charge). As noted by p. 5 of the instant Specification, the oligopeptide or the peptidomimetic compound exhibits good water solubility. As noted by pp. 7-8 of the Specification, elamipretide is an oligopeptide. Accordingly, one of ordinary skill in the art would reasonably expect the elamipretide of Schiffman to possess substantially the same properties as the claimed invention, such as being positively charged in aqueous buffered solution at neutral pH, or being water soluble.
Regarding claims 4, 6 and 9, as discussed above, Schiffman discloses wherein the silica hydrogel composite comprises up to 85 wt. % of said silica particles (Jokinen: [0022]). Accordingly, the claimed amounts of microparticles (i.e. from about 30 to about 95 wt. %; about 80 wt. %; and about 50 wt. %, respectively) would have been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art (i.e. up to 85 wt. %). 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). Moreover, in any case, the selection of appropriate weight percentages would appear to require no more than routine testing on the part of the skilled artisan, and so alternative it would have taken no more than the relative skills of one of ordinary skill in the art to have determined workable ranges to arrive at the claimed amounts of silica particles. "[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." See MPEP § 2144.05(II)(A).
Regarding claim 11 reciting an amount of freebase equivalent of the oligopeptide or peptidomimetic compound, it would have been obvious to one of ordinary skill in the art to have selected an amount of active agent from the disclosed range of 0.1 to 70 wt. %, which appears to equate to a freebase equivalent amount that would overlap with the instantly claimed amounts in freebase equivalent (i.e. from about 0.1 wt. % to about 10 wt. %). 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). Moreover, in any case, the selection of appropriate weight percentages would appear to require no more than routine testing on the part of the skilled artisan, and so alternative it would have taken no more than the relative skills of one of ordinary skill in the art to have determined workable ranges to arrive at the claimed amounts of freebase equivalent of the oligopeptide or peptidomimetic compound. "[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." See MPEP § 2144.05(II)(A).
Regarding claims 17-18 and 54 reciting wherein the formulation: can be injected from a syringe having an attached needle; wherein the needle thickness is 25-30 gauge; or is prepackaged in a syringe and needle configuration for single-use intravitreal injection, respectively, these are merely recitations of intended use of the formulation. Since the delivery system of the prior art comprises substantially the same active ingredients as the claimed invention (i.e. shear-thinning silica hydrogel composite), the delivery system of the prior art would be usable to be injected from a syringe having an attached needle, wherein the needle is 25-30 gauge in thickness, or prepackaged in a syringe and needle configuration for single-use intravitreal injection, whether the prior art recognizes such use or not.
Regarding claim 20 reciting a pH range, the claimed ranges (i.e. from about 4.0-7.5) would have been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art (i.e. 5.5-5.9). 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). Moreover, in any case, the selection of appropriate pH value would appear to require no more than routine testing on the part of the skilled artisan, and so alternative it would have taken no more than the relative skills of one of ordinary skill in the art to have determined workable ranges to arrive at the claimed values of pH. "[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." See MPEP § 2144.05(II)(A).
Regarding claim 23, Schiffman further discloses wherein mitochondrial peptides may include humanin (i.e. an oligopeptide) ([0018]). Accordingly, a composition comprising more than 1 oligopeptide would have also been obvious.
Regarding claims 24-25, as discussed above, Schiffman discloses wherein the drug delivery system contains elamipretide. Therefore one of ordinary skill in the art would reasonably expect the elamipretide of Schiffman to possess substantially the same properties as the claimed invention, such as having a structure as recited.
Regarding claim 34, Schiffman further discloses wherein the drug delivery system may be administered to treat Familiar Exudative Vitreoretinopathy ([0094]). Accordingly, since Schiffman teaches treating vitreoretinopathy, intravitreal administration would flow from such teaching.
Regarding claims 55-57, the claims are drawn to a product-by-process as evidenced by the recitation “formed using a … process” in claim 55. Accordingly, the claims are interpreted as not requiring the steps set forth in the claims, but only the structure implied by the steps. See MPEP § 2113.
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 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,252,553, claims 1-8 of U.S. Patent No. 11,555,053, and claims 1-15 of U.S. Patent No. 10,683,326 in view of Schiffman et al. (WO 2019/246141 A1, 12/16/219, IDS reference) (hereinafter Schiffman).
The patented claims differ from the pending claims insofar as not explicitly teaching all the features of the claimed invention, such as instantly claimed biodegradable silica hydrogel composite.
However, these feature are known in the art. As noted in the current rejections, the teachings of Schiffman render obvious claims 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57.
Therefore, as claims 1-8 of U.S. Patent No. 12,252,553, claims 1-8 of U.S. Patent No. 11,555,053, claims 1-15 of U.S. Patent No. 10,683,326, and Schiffman all disclose compositions comprising elamipretide, it would have been prima facie obvious to one of ordinary skill in the art to have modified the patented claims and to include the teachings of Schiffman as discussed in the rejections above, because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as instantly claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See MPEP 2144.06(I).
Claims 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-10, 13-18, 22-24, 28-33 of copending Application No. 18/010,526 and claims 14-29 and 46-47 of copending Application No. 19/053,773 in view of Schiffman et al. (WO 2019/246141 A1, 12/16/219, IDS reference) (hereinafter Schiffman).
The copending claims differ from the pending claims insofar as not explicitly teaching all the features of the claimed invention, such as instantly claimed biodegradable silica hydrogel composite.
However, these feature are known in the art. As noted in the current rejections, the teachings of Schiffman render obvious claims 1-4, 6, 9, 11, 17-20, 23-25, 33-34, and 54-57.
Therefore, as claims 1-2, 4, 6-10, 13-18, 22-24, 28-33 of copending Application No. 18/010,526, claims 14-29 and 46-47 of copending Application No. 19/053,773, and Schiffman all disclose sustained release compositions comprising elamipretide or compositions comprising elamipretide, it would have been prima facie obvious to one of ordinary skill in the art to have modified the copending claims and to include the teachings of Schiffman as discussed in the rejections above, because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as instantly claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See MPEP 2144.06(I).
This is a provisional nonstatutory double patenting rejection.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Leino et al. (US 2018/0311150 A1, 11/1/2018, IDS reference), directed to shear-thinning hydrogels.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUCY TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Thursday 8:30 AM - 6:30 PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SAHANA KAUP can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612