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
Applicant’s election of Group (I) with the addition of phosphatidylglycerol as the elected amphipathic lipid species and tricaprylin as the neutral lipid species in the reply filed on 05/14/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 10-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
This application is a continuation of U.S. Application No. 18/104,970, filed February 2, 2023, which claims the benefit of U.S. Provisional Application No. 63/422,182, filed November 3, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/22/2024, 07/08/2024, 08/08/2024, 09/26/2024, 01/08/2025, 04/08/2025, 05/29/2025, & 06/25/2025 has been considered by the examiner.
Status of Claims
Claims 1-5, 7, 10-15, 18-21, 23-24, and 31-33 are pending. Claims 10-15 are withdrawn. Claims 6, 8-9, 16-17, 22, and 25-30 are canceled. Claims 1-5, 7, 18-21, 23-24, and 31-33 are under examination.
Claim Objections
Claims 5 and 23 are objected to because of informal language. Specifically, claims 5 and 23 recite that “insertion of the injection needle into the leg of the patient comprises piercing the sciatic nerve sheath.” The phrase comprises piercing” is awkward and renders the claims informal. Appropriate correction may be made by amending the claims to recite “wherein insertion of the injection needle into the lag of the patient pierces the sciatic nerve sheath.” Or equivalent language.
Claim 20 is objected to because of informal language. Claim 20 recites “the entry point of the injection needle is into a lateral thigh of the patient.” The phrase “into” is grammatically improper and renders the claim informal. Appropriate correction may be made by amending the claims to recite “wherein the entry point for the injection needle is in the lateral thigh of the patient,” or equivalent language.
Claims 32 and 33 are objected to because of informal language. Claims 32 and 33 recite “the pharmaceutical composition is administered as a single dose administration.” The phrase “single dose administration” is grammatically redundant and renders the claim informal. Appropriate correction may be made by amending the claims to recite “administered as a single dose,” or equivalent language.
Claim 31 is objected to because of informal language. Claim 31 recites “mixing 10 mL bupivacaine multivesicular liposomes containing 133 mg of bupivacaine with 20 mL saline.” The phrase “10 mL bupivacaine multivesicular liposomes” is awkward and may be interpreted as modifying the liposomes themselves rather than the pharmaceutical composition containing the liposomes. Appropriate correction may be made by amending the claims to recite “mixing 10 mL of a pharmaceutical composition comprising bupivacaine multivesicular liposomes containing 133 mg of bupivacaine with 20 mL saline,” or equivalent language.
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 1-5, 7, 18-21, 23-24, and 31-33 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.
Claims 1 and 10 recite that the multivesicular liposomes comprise “bupivacaine or phosphate salt thereof” and further recite that “the pharmaceutical composition comprises 133 mg bupivacaine.” It is unclear whether the recited amount of 133 mg refers to 133 mg bupivacaine free base, 133 mg of the phosphate salt, or 133 mg expressed as a bupivacaine free-base equivalent when the phosphate salt is employed. Because the claims encompass both bupivacaine and a phosphate salt thereof but fail to specify the basis upon which the recited amount is measured, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the claimed subject matter.
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.
Claims 1-5, 7, 18-21, 23-24, and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over FDA-approved prescribing information for EXPAREL®, April 2018 or 2019 according Wayback machine), cited herein as “FDA label” in view of Creech et al. (The Journal of Foot & Ankle Surgery, 52:681-685 (2013)).
FDA label teaches EXPAREL® (bupivacaine liposome injectable suspension) comprising multivesicular liposomes containing bupivacaine encapsulated within liposomes having lipid components, including cholesterol, 1,2-dipalmitoyl-sn-glycero-3 phospho-rac-(1-glycerol) and tricaprylin. (See First paragraph under “Description” Section of page 18; and first paragraph of page 19; Dosage Forms, Strengths, and Administration Sections.) 1,2-dipalmitoyl-sn-glycero-3 phospho-rac-(1-glycerol) taught by the prior art constitutes an amphipathic lipid and is a species phosphatidylglycerol because the specification at paragraph [0019] discloses phosphatidylglycerols as suitable amphipathic lipids. The tricaprylin taught by the prior art represents a neutral lipid according the specification at paragraph [0020]. Moreover, FDA label teaches that EXPAREL® is supplied as a 133 mg/10mL single-dose vial and is intended for single-dose administration only for a maximum of 30 mL. (See Sections 2.1, 2.2, and 3.) FDA label also teaches the suspension may be diluted with preservative-free normal saline and diluting the recommended dose of EXAPREA generally 1 to 2 mL per injection for the 133 mg (10ml) for interscalene brachial plexus nerve block. (See Section 2.2 and 2.3.) The 2-mL injection of 133 mg/10 mL can amount to 20 mg and where the dilution involves saline. FDA label further teaches uses in patients undergoing bunionectomy and administration by injection using an appropriate needle. (Sections 2.2 and 14.1.) However, although the FDA label states safety and efficacy had not been established in nerve blocks other than interscalene brachial plexus nerve block (Section 1), the FDA label nevertheless teaches that EXAPAREL® liposomal bupivacaine composition and its use for postsurgical analgesia. (See section 1.) Encapsulation of the liposome is expressly taught at the second paragraph of page 19. Lastly, FDA label teaches after injection of EXPAREL bupivacaine is released from the multivesicular liposomes over a period of time. (See Section 11 under Description section.)
The FDA label does not teach administration to a sciatic nerve in the popliteal fossa.
Creech teaches popliteal sciatic nerve block techniques, including a sciatic nerve block in the popliteal fossa as adjunct method to improve efficacy and reproducibility for preoperative setting, insertion of an injection needle into the leg, a lateral approach through the lateral thigh, and administration to the tibial nerve and common peroneal nerve components in the popliteal fossa for effective and efficient use of regional anesthesia represents an essential component of perioperative pain management for foot and ankle reconstructive surgeons. Peripheral nerve blockade has been clearly demonstrated to be useful in minimizing acute and chronic postoperative pain, reducing narcotic consumption, and decreasing the morbidity associated with foot and ankle surgery and further teaches anatomical relationships and needle advancement procedures for obtaining blockage. (See Title, Abstract, and page 682) Creech also teaches the popliteal fossa also contains a relatively increased amount of accessory adipose tissue relative to other areas of the foot and ankle, making it an ideal repository location fora bolus injection considering that bupivacaine becomes tightly bound to adipose. This likely contributes to the noted increased duration of action for a block performed in this location. (See second paragraph of the right column of page 681.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the known EXPAREL® liposomal bupivacaine formulation by the known popliteal fossa sciatic nerve block techniques taught by Creech because both references are directed toward achieving post-operative regional analgesia using local anesthetic techniques. One of ordinary skill in the art would have reasonably expected that administration of a known sustained-release bupivacaine formulation by a known sciatic nerve block technique would provide prolonged postoperative analgesia while utilizing recognized anatomical landmarks and established injection procedures. Combining prior art methods to known techniques to obtaining predictable results constitutes obviousness. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (20070.
Although FDA label states that the safety and efficacy of EXPAREL® had not been established in nerves blocks other than interscalene brachial plexus nerve block (Sedition 8.4), such statement merely reflects the scope of the approved indication and does not criticize, or discourage use in other peripheral nerve blocks. Creech teaches that the popliteal fossa contains an increased amount of accessory adipose tissue, make the location an ideal repository for bolus injection because bupivacaine becomes more tightly bound to adipose tissue, thereby contributing to an increase duration of action. (See second paragraph of the right column of page 681.) Creech further teaches that complete anesthesia is achieved by performing regional blockade within the common epineural sheath before division of the tibial and common peroneal nerves. Accordingly, one of ordinary skill in the art would have been motivated to administer the known sustained-release liposomal bupivacaine formulation taught by the FDA label using the known popliteal sciatic nerve block technique taught by Creech in order to achieved prolonged postoperative regional analgesia with a reasonable expectation of success.
With respect to claims 5 and 23, Creech teaches that the tibial nerve and common peroneal nerve share a common epineural sheath until their division and further teaches that, in order to ensure complete anesthesia, regional blockade should be performed before the division and within the common epineural sheath. Creech additionally teaches that blockade within the common epineural sheath may be achieved through either a posterior or lateral approach. (See first paragraph of the right column of page 681.) The FDA label teaches a known anesthetic formulation comprising liposomal bupivacaine for providing prolonged postoperative analgesia. Accordingly, it would have been obvious to one of ordinary skill in the art to administer the known liposomal bupivacaine formulation taught by the FDA label using the popliteal sciatic nerve block technique taught Creech and would have had a reasonable expectation of success in doing so.
Because Creech teaches that complete anesthesia is achieved by administering the anesthetic within the common epineural sheath, performing the combined teachings would necessarily require the injection needle to penetrate or pierce the sciatic nerve sheath to deposit the multivesicular liposome formulation therein. Therefore, the combined teaches of the FDA label and Creech would have resulted in insertion of the injection needle into the leg of the patient comprising piercing the sciatic nerve sheath.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-5, 7, 18-21, 23-24, and 31-33 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,918,565B1. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the U.S. patent anticipate the instant claims.
The claims of the U.S. patent teach a method of administering regional analgesia comprising a sciatic nerve block in the popliteal fossa of a patient, the method comprising:
a) selecting an entry point of an injection needle in a leg of the patient;
b) inserting the injection needle into the patient at the entry point;
c) administering to a sciatic nerve sheath of the patient via the injection needle 133 mg of a pharmaceutical composition;
wherein the pharmaceutical composition comprises multivesicular liposomes comprising:
at least one amphipathic lipid, at least one neutral lipid, and bupivacaine phosphate, wherein the bupivacaine phosphate is encapsulated within the multivesicular liposome,
thereby administering the regional analgesia comprising the sciatic nerve block in the popliteal fossa of the patient. (See claim 1.) The insertion of the injection needle into the leg of the patient comprises piercing the perineural sheath, wherein the entry point of the injection needle is in the lateral thigh, and wherein the method comprises administering about 30 mL of the pharmaceutical composition. (See claims 5-7.)
The U.S. patent claims also teach a method of administering to a peroneal and a tibial nerve of a human patient a pharmaceutical composition for post-operative analgesia, the method comprising:
a) selecting an entry point of an injection needle in a leg in a patient;
b) advancing a needle tip of the injection needle within a region where the sciatic nerve splits into the peroneal and tibial nerves of the patient along a trajectory that extends between the entry point and where the sciatic nerve splits into the peroneal and tibial nerves;
c) administering to said region through the injection needle 133 mg of a pharmaceutical composition;
wherein the pharmaceutical composition comprises multivesicular liposomes comprising:
at least one amphipathic lipid, at least one neutral lipid, and bupivacaine phosphate, wherein the bupivacaine phosphate is encapsulated within the multivesicular liposome,
thereby administering to the peroneal and the tibial nerve of the human patient the pharmaceutical composition for post-operative analgesia, wherein the entry point of the injection needle is in the lateral thigh. (See claims 10-14.)
Conclusion
Claims 1-5, 7, 18-21, 23-24, and 31-33 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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