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 .
Information Disclosure Statement
The information disclosure statement filed 31 March 2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Election/Restrictions
Applicant's election with traverse of Group I drawn to an echogenic composition in the reply filed on 31 March 2025 is acknowledged. The traversal is on the ground(s) that there is no serious examination burden to search the inventions of Groups I and II. This is not found persuasive because such a burden does exist, as additional searches would be required to identify the method of Group II compared to the composition of Group I (e.g., further search and consideration would be required to locate art on the method step of confirming delivery of the composition with ultrasound).
As such, the requirement is still deemed proper and is therefore made FINAL.
Claims 1-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 31 March 2025.
Applicant's election with traverse of ropivacaine as the species of anesthetic, hyaluronic acid as the species of emulsifier, glycerol as the species of polyol, and a species of composition further comprising a phospholipid in the reply filed on 31 March 2025 is acknowledged. The traversal is on the ground(s) that there is no search or examination burden for the species. This is not found persuasive because such a burden does exist. The genera of anesthetic, emulsifier, and polyol are all broad and contain a large variety of species that differ significantly in chemical structure and would require searching different classes/subclasses. Further, the different species of composition would require additional searches for the additional ingredients (e.g., additional searches would be required to identify compositions further comprising an antioxidant).
As such, the requirement is still deemed proper and is therefore made FINAL.
Upon further search and consideration, art was found that reads on bupivacaine as the species of anesthetic. As such, bupivacaine alone will be rejoined and examined together. The election of species is maintained to the extent that there exists a serious search and examination burden to consider the remaining species.
Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 31 March 2025.
Claims 15-17 and 19-20 are examined on the merits herein.
Claim Objections
Claim 15 is objected to because of the following informalities:
“wherein an undissolved crystalline agent within the triglyceride” in line 4 should read “wherein an undissolved crystalline agent is present within the triglyceride”
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 16-17 and 19 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 16 recites hyaluronic acid present in an amount from about 0.15% to about 1% without defining what the percentage is with respect to (e.g., %w/v of the composition, %w/w of the aqueous phase, etc.), rendering the claim indefinite. For examination purposes, claim 16 is interpreted as “The composition of claim 15, wherein the emulsifier is hyaluronic acid present in an amount from about 0.15% to about 1% (w/v) of the composition.
Claim 17 recites the lipid phase further comprising a phospholipid present in an amount from about 0.1% to about 2.0% of the lipid phase, without defining the quantity represented by the percentage (e.g., %w/v, %w/w, etc.), rendering the claim indefinite. For examination purposes, claim 17 is interpreted as “The composition of claim 15, wherein the lipid phase further comprises a phospholipid present in an amount from about 0.1% to about 2.0% (w/w) of the lipid phase.”
Claim 19 recites the lipid phase is from about 10% to about 40% (w/v)without defining what the percentage defines (e.g., the lipid phase is present in about 10% to about 40% (w/v) of the composition, the lipid phase is from about 10% to about 40% (w/v) triglycerides, etc.) rendering the claim indefinite. For examination purposes, claim 19 is interpreted as “The composition of claim 15, wherein the lipid phase is present in an amount from about 0.15% to about 1% (w/v) of the composition.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 15-16 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Davis et al. (Int. J. Pharm., 2020, Vol. 588, 119703) in view of Shekunov et al. (J. Crystal Growth, 2000, Vol. 211, 122-136), and Niederwanger et al. (J. Pharm. Sci., 2009, Vo. 98, 1064-1074) as evidenced by FDA (“Intralipid®”) and PubChem (“Soybean Oil”).
Claim 15 is drawn to an echogenic composition for the treatment of pain comprising: a continuous aqueous phase comprising an emulsifier and a polyol;
a lipid phase comprising a triglyceride, wherein the triglyceride is liquid at 25°C and wherein an undissolved crystalline anesthetic agent within the triglyceride; and wherein the lipid phase is emulsified within the continuous aqueous phase.
Claim 16 is drawn to the composition of claim 15, wherein the emulsifier is hyaluronic acid present in an amount from about 0.15% to about 1%.
Davis et al. teach an emulsion comprising the anesthetic bupivacaine (Abstract) comprising bupivacaine and Intralipid® dispersed in an aqueous phase comprising 1.25% hyaluronic acid, water, and glycerol (Pg. 2 left column fourth paragraph).
As such, Davis et al. teach a continuous aqueous phase comprising 1.25% w/v hyaluronic acid and glycerol; a lipid phase comprising Intralipid®, wherein an anesthetic agent is present within the lipid phase, and wherein the lipid phase is emulsified within the continuous aqueous phase.
The composition of Davis et al. differs from the instantly claimed invention in the following ways:
Davis et al. are silent as to the presence of a triglyceride;
Davis et al. are silent as to the state of matter of the lipid phase at 25°C;
Davis et al. do not teach a crystalline anesthetic agent;
Davis et al. are silent as to the composition being an echogenic composition; and
Davis et al. do not teach hyaluronic acid present in an amount from about 0.15% to about 1%.
Yet, as to 1 and 2: As evidenced by FDA, Intralipid® comprises soybean oil. As further evidenced by PubChem, soybean oil comprises a mixture of triglycerides (“Description” on pg. 1), melts between 22-31°C, and solidifies below 16°C (“3.1.6 Melting Point”) i.e., is a liquid at 25°C.
As to 3: Davis et al. further teach “Further shelf-life testing was not performed in this study and will need to be validated in the future to determine if the ready-to-use preparation can have sufficient shelf-life stability required for FDA approval” (Pg. 5 right column).
Shekunov et al. teach that crystallization plays an important role in defining the stability properties of dosage forms of drugs (Abstract). Niederwanger et al. teach crystal forms of bupivacaine (Title). Niederwanger et al. further teach that crystal forms A and D of bupivacaine have high stability and can remain unchanged even after a storage period of a year (Pg. 1066 left column first and last paragraphs).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Davis et al. to comprise crystalline bupivacaine. It would have been obvious to combine the known bupivacaine emulsion and the known stable crystalline form of bupivacaine to yield the predictable result of a bupivacaine emulsion with improved active ingredient stability, with a reasonable expectation of success.
As to 4: As discussed in MPEP 2112.01(II), "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
In the instant case, the echogenicity of the composition is a property inherent to the instantly claimed composition as evidenced by the instant specification at Pars. [0159-160] and Figs. 39-4. As Davis et al. in view of Shekunov et al. and Niederwanger et al. teach all of the structural limitations of claim 15, the instantly claimed echogenicity is necessarily present.
And, as to 5: As discussed in MPEP 2144.05(I), Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985), "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."
In the instant case, a composition comprising about 1% w/v of hyaluronic acid and a composition comprising 1.25% w/v hyaluronic acid are so close that one of ordinary skill in the art would reasonably expect them to have the same properties.
Based on all of the foregoing, claims 15-16 are rejected as prima facie obvious.
Claim 19 is drawn to the composition of claim 15, wherein the lipid phase is from about 10% to about 40% (w/v).
Davis et al. further teach the composition comprising 15% w/v of Intralipid® (Pg. 2 left column fifth paragraph) i.e., the lipid phase, overlapping with the instantly claimed range.
As such, claim 19 is also rejected as prima facie obvious.
Claim 20 is drawn to the composition of claim 15, wherein the polyol is glycerol and is present in an amount of from about 0.25 to about 2.5% (w/v) of the composition.
Davis et al. further teach the composition comprising 2.25% w/v glycerol (Pg. 2 left column fifth paragraph), overlapping with the instantly claimed range.
As such, claim 20 is also rejected as prima facie obvious.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Davis et al., Shekunov et al., and Niederwanger et al. as evidenced by FDA and PubChem as applied to claims 15-16 and 19-20 above, and further in view of Pichot et al. (Int. J. Mol. Sci., 2013, Vol. 14, 11767-11794).
The teachings of Davis et al., Shekunov et al., and Niederwanger et al. have been set forth above.
Claim 17 is drawn to the composition of claim 15, wherein the lipid phase further comprises a phospholipid present in an amount from about 0.1% to about 2.0% of the lipid phase.
As further evidenced by FDA, Intralipid® further comprises egg yolk phospholipids (“Description”). As such, the lipid phase of Davis et al. further comprises a phospholipid.
Davis et al., Shekunov et al., and Niederwanger et al. do not teach the lipid phase comprising about 0.1% to about 2.0% of the phospholipid.
However, Pichot et al. teach that phospholipids are used as emulsion stabilizers due to their amphiphilic character, indicating that the stability of the emulsion is directly related to the concentration of phospholipids present.
And as discussed by MPEP 2144.05, “[g]enerally, 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” (see also In re Aller (220 F.2d 454)): “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…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the concentration of the phospholipid is clearly a result-effective variable, determining the stability of the emulsion. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal concentration of the phospholipid in order to best achieve the desired results.
As such, claim 17 is rejected as prima facie obvious.
Claim 15 is FURTHER rejected under 35 U.S.C. 103 as being unpatentable over Davis et al., Shekunov et al., and Niederwanger et al. as evidenced by FDA and PubChem as applied to claims 15-16 and 19-20 above, and further in view of Li et al. (Int. J. Nanomed., 2019, Vol. 14, 913-920).
Claim 15 is drawn to an echogenic composition for the treatment of pain comprising: a continuous aqueous phase comprising an emulsifier and a polyol;
a lipid phase comprising a triglyceride, wherein the triglyceride is liquid at 25°C and wherein an undissolved crystalline anesthetic agent (more specifically ropivacaine (Applicant’s elected species)) within the triglyceride; and wherein the lipid phase is emulsified within the continuous aqueous phase.
Davis et al., Shekunov et al., and Niederwanger et al. teach all of the limitations of claim 15 as discussed above, but do not teach the composition comprising Applicant’s elected species of ropivacaine.
Davis et al. further teach the composition being an injectable composition (Abstract).
Li et al. teach a composition for the delivery of encapsulated ropivacaine (Abstract) by injection (Pg. 916 left column second paragraph). Li et al. further teach that ropivacaine “has a longer analgesic effect(3–6 hours) and lower CNS toxicity and cardiotoxicity” compared to other local anesthetics (Pg. 914 left column third paragraph).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the composition of Davis et al. to comprise ropivacaine as taught by Li et al. It would have been obvious to substitute one local anesthetic suitable for delivery by injection for another to obtain the predictable result of an anesthetic composition with longer analgesic effect and lower toxicity, with a reasonable expectation of success.
As such, claim 15 is rejected as prima facie obvious.
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 15-17 and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 6-9 of copending Application No. 18/631,935 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of Application No. ‘935 recites a composition for treating pain in a subject, comprising: an emulsion comprising: an aqueous carrier; and a liquid lipid phase dispersed into droplets within the aqueous carrier, and a first anesthetic within the lipid phase. Claims 2-3 of Application No. ‘935 recite the composition of claim 1, wherein the anesthetic is a plurality of anesthetic crystals in the lipid phase. Claim 6 of Application No. ‘935 recites the composition of claim 1, wherein the lipid phase comprises a triglyceride. Claim 7 of Application No. ‘935 recites the composition of claim 1, wherein the aqueous carrier further comprises hyaluronic acid and glycerol. Claim 8 of Application No. ‘935 recites the composition of claim 1, wherein the lipid phase further comprises a phospholipid present in an amount of from 0.1% to 2.0% of the lipid phase. Claim 9 of Application No. ‘935 recites the composition of claim 1, wherein the lipid phase is from about 10% to about 40%.
Claims 1-3 and 6-9 of Application No. ‘935 overlap with instant claims 15-17 and 19-20.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/PAUL HOERNER/Examiner, Art Unit 1611