DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Status of the Claims
The response filed 11/10/2025 is acknowledged.
Claims 1-19 and 31-32 are pending.
Claims 8-9 and 16-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/08/2023.
Claims 1-7, 10-15, and 31-32 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Withdrawn
The rejection of claims 1-6 and 10-14 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joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention has been withdrawn because of Applicant’s amendment.
The rejection of claims 1-6 under 35 U.S.C. 103 as being unpatentable over Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2) has been withdrawn because of Applicant’s amendment. Syringe was deleted from claim 1.
Response to Arguments
Applicant’s arguments with respect to claim(s) 11/10/2025 have been considered but are not persuasive.
Regarding the rejection of claims 1-6 and 10-14 based on the combined teachings of Villalobos and Mulier alone or further in view of During:
Applicant argues Villalobos discloses a multi-drug regimen (separate administrations) rather than a pre-mixed composition, as claimed. Applicant argues Mulier discloses obtaining anesthetics from a syringe, yet Mulier does not disclose a composition comprising a Mg salt. Applicant argues none of these references discloses a reason to combine their teaching and to use Mulier's syringe to arrive at the claimed invention with a reasonable expectation of success. Applicant argues that even combined, the cited references do not disclose the claimed invention.
These arguments are unpersuasive.
There is nothing in Villalobos which teaches the ingredients are administered separately.
To the extent that Villalobos does not teach the ingredients in an IV bag, bottle, or a vial, Mulier teaches a similar composition in a single container, e.g., a syringe which is useful for containing the ingredients of an opioid free anesthesia mixture containing dexmedetomidine, ketamine, and lidocaine.
To the extent that Villalobos does not teach the mixture in an IV bag, a bottle, or a vial, During teaches syringes and vials were known alternatives for containing anesthetic mixtures.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant has argued Hindsight is impermissible and short of hindsight there is no reason to randomly combine these references. See MPEP § 2145; Gore v. Garlock, 721 F.2d 1540, 1552 (Fed. Cir. 1983) (stating that there must be a legitimate rationale to take the steps the examiner proposes-without using the claim as a "frame" to employ "individual naked parts of separate prior art references... as a mosaic to recreate a facsimile of the claimed invention."). The Applicant's own invention cannot impermissibly be used "...as a guide through the maze of prior art references, combining the right references in the right way so as to achieve the result of the claims." See Orthopedic Equipment Co. v. United States, 702 F.2d 1005, 1012 (Fed. Cir. 1984) (emphasis added).
These arguments are unpersuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Here it is noted that the references were not randomly combined. Each reference is clearly directed to solving the same problem, i.e., formulating injectable compositions. Both Villalobos and Mulier specifically teach opioid free anesthetic compositions. Mulier specifically teaches combining opioid free anesthetic ingredients in a single container, e.g., a syringe to facilitate administration. During clearly teaches syringes or vials were art recognized equivalent containers for containing injectable compositions.
Regarding the rejection of claims 1 and 7 under 35 U.S.C. 103 as being unpatentable over Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2) and During, US 20180235942 A1 as applied to claims 1-6 above and further in view of Worthington, US 20200230120 A1 and Magnesium_Sulfate_Injection_Sep_20_2017 (“Magnesium Sulfate”).
Applicant has argued Worthington is non-analogous art. Worthington discloses a formulation comprising a local anesthetic (such as Bupivacaine HCl), an NMDA receptor antagonist (such as Ketamine HCl) and a COX inhibitor (such as Ketorolac Tromethamine) for preventing nausea and vomiting after surgery and to enhance post-operative pain relief, and not for use as a pre-operative or an inter-operative pharmaceutical composition as claimed. Applicant argues a person of ordinary skill in the art would never administer Bupivacaine HCl intravenously, as it would cause local anesthesia toxicity (LAST). A person of ordinary skill in the art would thus have no reason to combine this non-analogous art's disclosure with those of the other cited references. Adding Worthington appears only due to impermissible hindsight reconstruction.
These arguments are unpersuasive.
The claimed invention is directed to a composition rather than a method of use. The claimed invention does not require administering bupivacaine intravenously. Worthington is not limited to compositions comprising a local anesthetic which cannot be given intravenously. None of Worthington’s composition claims require bupivacaine (Worthington, e.g., claims 1-6). Worthington, e.g., claim 4 shows lidocaine as used in Villalobos was a known alternative for bupivacaine. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP 2123, II.
Worthington teaches an anesthetic/analgesic formulation, which is opioid free (Worthington, e.g., Abstract). Therefore, Worthington is in the same field of endeavor as the present application.
Worthington was cited for suggesting effective amounts of a corticosteroid may be present in an anesthetic composition. Worthington teaches opioid free compositions like those of Villalobos, wherein the composition is modified with a corticosteroid, e.g., dexamethasone, in an amount of from 0.1 to 1 mg/mL (Worthington, e.g., 0062 and claim 2). Steroids counteract inflammatory processes triggered by surgery (Worthington, e.g., 0004-0005, 0016, and 0062). Thus, Worthington provides a teaching which would have prompted the skilled artisan to modify compositions suggested by Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2) and During, US 20180235942 A1 by including dexamethasone to counteract inflammatory processes during surgery.
Regarding the rejection of claim 31 based on Mauermann, Best Practice and Research Clinical Anesthesiology, 31, 2017 in view of Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant's IDS dated 05/31/2022) in view of During, US 20180235942 Al:
Applicant has argued the cited references do not disclose a vial containing the claim-recited anesthetics. Applicant acknowledges vials are used in the art as container. Applicant argues the claimed invention relates to a vial because the vial allows a practitioner to make use the anesthetics without needing to consider dosage, type of anesthetic, etc. Applicant argues different vials can comprise different actives and at different dosages. Applicant argues nothing in the cited references suggests to the person of ordinary skill in the art to make use of a vial, or that using a vial is advantageous. Applicant argues short of hindsight there is no reason to randomly combine these teachings.
These arguments are unpersuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
As evident from During, the skilled artisan understood that predetermined amounts of pharmaceutical ingredients may be contained in a bag, vial or bottle, and even stored in these containers (During, e.g., 0045, 0048-0049). Further, the containers are suitable for dispensing sterile parenteral formulations (During, e.g., 00075) because, e.g., pre sterilized vials may be filled with appropriate amounts of sterile blends of pharmaceutical ingredients (During, e.g., 0073).
Rejections Addressing Applicant’s Amendment
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.
Claim 15 is 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 15 includes the limitation of optionally, one or more of an NMDA antagonist other than the magnesium salt, and a beta-blocker. However, claim 15 also includes the limitation of a beta-blocker in an amount ranging from about 0.15 mg/mL to about 2 mg/mL. The claim is inconsistent with respect to the beta blocker. The first limitation indicates the beta blocker is optional. The second limitation indicates the beta blocker is required in a specific concentration. The skilled artisan is unable to determine the metes and bounds for which applicant is claiming protection.
To overcome this rejection, claim 15 could state:
An opioid-free intra-operative pharmaceutical composition comprising:
a magnesium (Mg2) salt,
an alpha-2 agonist,
a sodium channel inhibitor, and
a beta-blocker, together with a pharmaceutically acceptable vehicle, carrier, or excipient, and optionally an NMDA antagonist other than the magnesium salt,
wherein the magnesium salt, alpha-2 agonist, sodium channel inhibitor, beta blocker, and optionally the one or more NMDA antagonist other than the magnesium salt are comprised in an effective amount to maintain anesthesia, sedation and/or analgesia and stable vital signs of the individual in the intra-operative stage of the medical or surgical procedure,
wherein said composition is contained in an IV bag, a bottle, or a vial,
wherein the composition comprises:
a magnesium salt in an amount ranging from about 5 mg/mL to about 20 mg/mL;
an alpha-2 agonist in an amount ranging from about 0.1 to about 1 mcg/mL;
a sodium channel inhibitor in an amount ranging from about 0.5 mg/mL to about 3 mg/mL;
an NMDA antagonist other than magnesium salt in an amount ranging from about 0 mg/ mL to about 0.5 mg/mL; and
a beta-blocker in an amount ranging from about 0.15 mg/mL to about 2 mg/mL, together with a pharmaceutically acceptable vehicle, carrier, or excipient.
Clarification is required.
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 of this title, 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.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2) and During, US 20180235942 A1.
Claim 1 requires a composition comprising a magnesium salt, and an alpha-2 agonist with a pharmaceutically acceptable vehicle, carrier, or excipient.
The recitation of pre-operative (claim 1) appears to be directed to an intended use of the composition, and have been interpreted as a recitation of intended use. The body of the claim clearly sets forth the required elements of the claimed invention.
Claims 3-6 further limit optional limitations of claim 1 from which they depend.
Villalobos teaches a composition comprising Ketamine 0.125 mg/kg IBW, Dexmedetomidine 0.5 ug/kg IBW, Lidocaine 1.5 mg/kg IBW, and Mg Sulfate 40 mg/kg (Villalobos, e.g., pg. S141). Said composition is useful for induction and maintenance of anesthesia, i.e., pre-operative and intra-operative. See Villalobos, e.g., pg. S141:
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Mg Sulfate is a magnesium salt. Dexmedetomidine is an alpha-2 agonist per instant claims 1-2, 6 and 10-11, and 14. Lidocaine is a sodium channel inhibitor per instant claims 1, 3, 6, 10, 12, and 14. Ketamine is an NMDA antagonist other than the magnesium salt as per instant claims 1, 4, 6, 10, and 13-14.
Instant claim 5 further limits the optional corticosteroid of claim 1. Instant claim 14 further limits the optional beta-blocker of claim 10. Neither claim 5 nor claim 14 require the optional feature of claim 1 or 10 from which they respectively depend.
Villalobos does not expressly teach the composition in an IV bag, a bottle or a vial.
Mulier teaches a syringe containing a similar opioid free anesthesia composition comprising a carrier (NaCl), dexmedetomidine (an alpha-2 agonist), ketamine (NMDA antagonist other than the magnesium salt), and lidocaine (a sodium channel inhibitor), which composition is expressly taught for induction (pre-operative as per claim 1) and maintenance (intra-operative as per claim 10). See Mulier, e.g., pg. 2/4:
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Mulier does not expressly teach the composition comprising a magnesium salt.
It would have been obvious before the effective filing date of the presently claimed invention to combine the teachings of Villalobos and Mulier to arrive at a composition within the scope of the claimed invention with a reasonable expectation of success. Starting from Villalobos, it would have been obvious to use the technique of formulating the OFA composition in a syringe as suggested by Mulier to improve the composition in the same way. The skilled artisan would have been motivated to formulate Villalobos’ induction and maintenance OFA composition in a syringe as suggested by Mulier to facilitate administration of their composition in the same way with a reasonable expectation of success. Alternatively, starting from Mulier, it would have been obvious to substitute one known OFA composition for another in the syringe to achieve predictable results. See MPEP 2144.06. Substitution of one known opioid free anesthesia composition for another to arrive at a syringe containing an opioid free anesthesia composition since both compositions are expressly taught by the prior art as useful for inducing and maintaining anesthesia. The skilled artisan would have had a reasonable expectation of success because each document teaches opioid free anesthetic compositions useful for treating patients undergoing surgery.
The combined teachings of Villalobos and Mulier teach the composition used in a method which requires dispensing the anesthetic composition to a patient but do not expressly teach the composition in a vial.
However, vials were known and used as alternative containers for anesthetic compositions as evident from the teachings of During. During clearly teaches vials or pre-filled syringes are suitable for dispensing sterile parenteral formulations (During, e.g., 0073-0075).
As evident from During, the skilled artisan understood that predetermined amounts of pharmaceutical ingredients may be contained in a bag, vial or bottle, and even stored in these containers (During, e.g., 0045, 0048-0049). Further, the containers are suitable for dispensing sterile parenteral formulations (During, e.g., 00075) because, e.g., pre sterilized vials may be filled with appropriate amounts of sterile blends of pharmaceutical ingredients (During, e.g., 0073).
It would have been obvious before the effective filing date of the presently claimed invention to modify a formulation suggested by the combined teachings of Villalobos and Mulier by formulating the composition in a vial with a reasonable expectation of success. During provides an express suggestion which would have prompted the skilled artisan to make this modification. The skilled artisan would have seen this modification as the selection of a known container for dispensing a parenteral anesthetic composition. See MPEP 2144.07. The skilled artisan would have found During’s teaching useful to facilitate dispensing the anesthetic composition suggested by Villalobos and Mulier with a reasonable expectation of success.
Accordingly, the subject matter of claims 1-6 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2) and During, US 20180235942 A1 as applied to claims 1-6 above and further in view of Worthington, US 20200230120 A1 and Magnesium_Sulfate_Injection_Sep_20_2017 (“Magnesium Sulfate”).
The combined teachings of Villalobos and Mulier and During teach a vial containing a composition according to claim 1 as enumerated above.
The combined teachings of Villalobos and Mulier and During teach a composition according to claim 1, but do not expressly teach the composition comprising a corticosteroid at a concentration ranging from about 0.1 mg/mL to about 10 mg/mL.
Worthington teaches opioid free compositions like those of Villalobos and Mulier, wherein the composition is modified with a corticosteroid, e.g., dexamethasone, in an amount of from 0.1 to 1 mg/mL (Worthington, e.g., 0062 and claim 2). Steroids counteract inflammatory processes triggered by surgery (Worthington, e.g., 0004-0005, 0016, and 0062).
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. The range in Worthington is entirely within the claimed range.
It would have been obvious before the effective filing date of the presently claimed invention to modify a composition known from Villalobos and Mulier and During by including a corticosteroid such as dexamethasone in an amount ranging from 0.1 to 1 mg/mL as suggested by Worthington with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification to enable the composition to counteract inflammatory processes triggered by surgery in the same way suggested by Worthington. The skilled artisan would have seen this modification as the use of a known technique to improve similar anesthetic/analgesic compositions in the same way. The skilled artisan would have had a reasonable expectation of success since Worthington teaches compositions effective for anesthesia and analgesia like Villalobos and Mulier and During.
The combined teachings of Villalobos and Mulier and During and Worthington teach the composition comprising magnesium sulfate (Villalobos), wherein the magnesium sulfate was a known NMDA antagonist (Worthington, e.g., 0026), and wherein the NMDA antagonist is present in a concentration of more than 3mg/mL and may exceed 10 mg/mL (Worthington, e.g., 0028). With respect to claims 7 and 15: The range of from about 50 mg/mL to about 500 mg/mL or from about 5 mg/mL to about 20 mg/mL is within the range suggested by Worthington for NMDA antagonists including magnesium sulfate.
Further in this regard, before the effective filing date of the presently claimed invention, magnesium sulfate for injection was known and used at a concentration of 50% - which is 500 mg/mL where 1% equals 10mg/mL (Worthington, e.g., 0019) – See Magnesium Sulfate, e.g., pg. 1. As indicated in the Magnesium Sulfate document, 500mg/mL should be diluted prior to IV administration (Magnesium Sulfate, e.g., pg. 1), to a suitable concentration for infusion, e.g., 10%-20% solution (Magnesium Sulfate, e.g., pg. 3/7: Dosage and Administration).
A concentration of 10% - 20% was understood to be a concentration of 100mg/mL – 200mg/mL using Worthington’s guidance for unit of concentration at ¶ 0019. The combined teachings of Villalobos and Mulier and During and Worthington and Magnesium Sulfate suggest a composition comprising magnesium sulfate at a concentration of from 1 mg/mL-about 200 mg/mL would be suitable for intravenous infusion. The claimed ranges for magnesium sulfate overlap with the range suggested by the prior art.
Regarding the additional amounts in recited in claims 7 and 15:
Mulier teaches dexmedetomidine in the syringe at a concentration of 50mcg/50mL, which is 1 mcg/mL. Worthington teaches alpha-2 agonist concentration ranging from about 8 mcg/mL to about 1 mcg/mL (Worthington, e.g., 0062: 0.008 mg/cc to 0.001 mg/cc). The claimed ranges overlap with the prior art ranges and Mulier teaches a value within the claimed range.
Mulier teaches lidocaine in the syringe at a concentration of 500mg/50mL which is 10 mg/mL and in the claimed range. Worthington teaches sodium channel inhibitor concentration, e.g., lidocaine, ranging from about 1mg/mL to about 5 mg/mL (Worthington, local anesthetic, e.g., lidocaine, prilocaine, and procaine at ¶ 0026; amounts for exemplary local anesthetics are found in ¶ 0027). The claimed ranges overlap with the prior art range.
Mulier teaches ketamine in the syringe at a concentration of 50mg/50mL which is 1mg/mL and close to the claimed range. Worthington teaches NMDA inhibitors, e.g., ketamine and/or magnesium sulfate (Worthington, e.g., 0026), are effective at concentrations between about 1-2 mg/mL or more than 3 mg/mL or more than 10 mg/mL (Worthington e.g., 0028). The claimed ranges overlap with the prior art 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. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
It would have been obvious before the effective filing date of the presently claimed invention to modify the composition in a vial suggested by the combined teachings of Villalobos and Mulier and During by optimizing the concentration of magnesium salt, alpha-2 agonist, sodium channel inhibitor NMDA antagonist other than magnesium salt (ketamine) and corticosteroid in the ranges suggested by Worthington and the Magnesium sulfate document with a reasonable expectation of success. The skilled artisan would have been motivated to optimize the amounts of active agents within the ranges suggested by the prior art to achieve a desired dose of each agent effective for anesthesia and pain control with reduced side effects depending on the patient weight, desired dose, and desired infusion rate with a reasonable expectation of success.
There does not appear to be any evidence of criticality associated with the ranges recited in claim 7.
Accordingly, the subject matter of claims 1 and 7 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claims 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of Mulier, OFAM, Mulimix, Jan 2019 (Cited on Applicant’s IDS dated 10/16/2024 as NPL 2).
Claim 10 requires a composition comprising a magnesium salt, an alpha-2 agonist, and a sodium channel inhibitor with a pharmaceutically acceptable vehicle, carrier, or excipient.
The recitation of intra-operative (claim 10) appears to be directed to an intended use of the composition, and have been interpreted as a recitation of intended use. The body of the claim clearly sets forth the required elements of the claimed invention.
Claims 13-14 further limit optional limitations of claim 10 from which they depend.
Villalobos teaches a composition comprising Ketamine 0.125 mg/kg IBW, Dexmedetomidine 0.5 ug/kg IBW, Lidocaine 1.5 mg/kg IBW, and Mg Sulfate 40 mg/kg (Villalobos, e.g., pg. S141). Said composition is useful for induction and maintenance of anesthesia, i.e., pre-operative and intra-operative. See Villalobos, e.g., pg. S141:
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Mg Sulfate is a magnesium salt. Dexmedetomidine is an alpha-2 agonist per instant claims 1-2, 6 and 10-11, and 14. Lidocaine is a sodium channel inhibitor per instant claims 1, 3, 6, 10, 12, and 14. Ketamine is an NMDA antagonist other than the magnesium salt as per instant claims 1, 4, 6, 10, and 13-14.
Instant claim 5 further limits the optional corticosteroid of claim 1. Instant claim 14 further limits the optional beta-blocker of claim 10. Neither claim 5 nor claim 14 require the optional feature of claim 1 or 10 from which they respectively depend.
Villalobos does not expressly teach the composition in a syringe, an IV bag, a bottle or a vial.
Mulier teaches a syringe containing a similar opioid free anesthesia composition comprising a carrier (NaCl), dexmedetomidine (an alpha-2 agonist), ketamine (NMDA antagonist other than the magnesium salt), and lidocaine (a sodium channel inhibitor), which composition is expressly taught for induction (pre-operative as per claim 1) and maintenance (intra-operative as per claim 10). See Mulier, e.g., pg. 2/4:
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Mulier does not expressly teach the composition comprising a magnesium salt.
It would have been obvious before the effective filing date of the presently claimed invention to combine the teachings of Villalobos and Mulier to arrive at a composition within the scope of the claimed invention with a reasonable expectation of success. Starting from Villalobos, it would have been obvious to use the technique of formulating the OFA composition in a syringe as suggested by Mulier to improve the composition in the same way. The skilled artisan would have been motivated to formulate Villalobos’ induction and maintenance OFA composition in a syringe as suggested by Mulier to facilitate administration of their composition in the same way with a reasonable expectation of success. Alternatively, starting from Mulier, it would have been obvious to substitute one known OFA composition for another in the syringe to achieve predictable results. See MPEP 2144.06. Substitution of one known opioid free anesthesia composition for another to arrive at a syringe containing an opioid free anesthesia composition since both compositions are expressly taught by the prior art as useful for inducing and maintaining anesthesia. The skilled artisan would have had a reasonable expectation of success because each document teaches opioid free anesthetic compositions useful for treating patients undergoing surgery.
Accordingly, the subject matter of claims 10-14 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Mauermann, Best Practice and Research Clinical Anesthesiology, 31, 2017 in view of Villalobos, ASMBS E-Poster Abstracts, Surgery for Obesity and Related Diseases, 14, 2018 (cited on Applicant’s IDS dated 05/31/2022) in view of During, US 20180235942 A1.
Claim 31 includes the limitations of a vial comprising an opioid-free pre-operative pharmaceutical composition comprising a magnesium salt comprising magnesium sulfate, an alpha- 2 agonist comprising dexmedetomidine, a sodium channel inhibitor comprising lidocaine, prilocaine or procaine, an NMDA antagonist comprising ketamine, and a corticosteroid comprising dexamethasone, wherein the magnesium sulfate, dexmedetomidine, lidocaine, prilocaine or procaine, ketamine, and dexamethasone are comprised in an effective amount in said vial for sedation and/or analgesia.
Mauermann teaches a composition comprising dexmedetomidine, ketamine, magnesium, lidocaine, and dexamethasone may be administered pre-operatively as a bolus. See Mauermann, e.g., pg. 538, Fig. 1.
Mauermann teaches dexamethasone offers prophylaxis for nausea and vomiting, anti-emesis and analgesia (Mauermann, e.g., pg. 539, Multimodal analgesia concept for bariatric surgery).
Mauermann teaches the composition comprising magnesium but does not expressly teach a magnesium salt.
Villalobos cures this defect because Villalobos teaches opioid free anesthesia compositions like those of Mauermann which comprise magnesium, wherein the magnesium is a magnesium salt, e.g., magnesium sulfate.
It would have been obvious before the effective filing date of the presently claimed invention to modify a composition for opioid free anesthesia known from Mauermann by formulating the magnesium as a magnesium salt with a reasonable expectation of success. The skilled artisan would have seen this modification as the selection of a known magnesium salt based on its art recognized suitability for use as an anesthetic. See MPEP 2144.07. The skilled artisan would have had a reasonable expectation of success because both documents teach opioid free anesthetic compositions.
The combined teachings of Mauermann and Villalobos teach the composition used in a method which requires dispensing the anesthetic composition to a patient but do not expressly teach the composition in a vial.
However, vials were known and used as alternative containers for anesthetic compositions as evident from the teachings of During. During clearly teaches vials or pre-filled syringes are suitable for dispensing sterile parenteral formulations (During, e.g., 0073-0075).
It would have been obvious before the effective filing date of the presently claimed invention to modify a formulation suggested by the combined teachings of Mauermann and Villalobos by formulating the composition in a vial with a reasonable expectation of success. During provides an express suggestion which would have prompted the skilled artisan to make this modification. The skilled artisan would have seen this modification as the selection of a known container for dispensing a parenteral anesthetic composition. See MPEP 2144.07. The skilled artisan would have found During’s teaching useful to facilitate dispensing the anesthetic composition suggested by Mauermann and Villalobos with a reasonable expectation of success.
Accordingly, the subject matter of claim 31 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
Claim 32 is are allowable.
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.
Correspondence
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
/SUSAN T TRAN/Primary Examiner, Art Unit 1615