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 .
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 05/13/2025has been entered.
DETAILED ACTION
Claims 1, 2, 5-15 and 17-31 are pending in the Claim Set filed 5/13/2025.
Claims 1 and 6 have been amended.
Applicants elected Group I: claims 1-25, in the reply filed on 5/30/2023. Applicants elected species of group (A) directed to even numbered fatty acids, and specifically, a mixture of stearic acid and oleic acid.
Claims 8, 11-14 of Group I and claims 26-31 of Group II are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 3, 4 and 16 are canceled.
Herein, claims 1, 2, 5-7, 9, 10, 15 and 17-25 are for examination.
Withdrawn Rejection
The rejection of claims 1, 2, 5-7, 9, 10, 15 and 17-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Quart et al (US 2020/0078363, cited in IDS filed 5/30/2023) in view of Beloqui et al (Nanostructured lipid carriers: Promising drug delivery systems for future clinics, 12 (2016) p.143), Taylor et al (U 20190175495, cited in IDS filed 5/30/2023), Mulvahill (US 2015/0359738, of record) and Rabinow et al (US20150024031) is withdrawn in favor of the new grounds of rejection as set forth below.
Objection Maintained
For consistency throughout the claims, claim 1 should be amended to recite ‘wherein the plurality of lipid microparticles are not liposomes” in the last line of claim 1 in the Claim Set filed 7/22/2024.
Applicants did not respond to this objection. Therefore, at this time, the objection is maintained.
Claim Rejections - 35 USC § 112
(Maintained Rejection)
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL - The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a New Matter rejection.
There is lack of written description for claim 21.
Claim 21 recites:
A composition for treating post-surgical pain comprising:
an aqueous carrier phase;
a first lipid phase comprising a plurality of lipid microparticles comprising an anesthetic agent and dispersed within the aqueous carrier phase; and
a second lipid phase comprising an anesthetic agent dissolved in one or more lipids and emulsified into to the aqueous phase,
wherein the composition treats local pain, and
wherein the plurality of lipid microparticles are not liposomes.
A complete search of Instant Specification did not provide support for the phrase ‘the composition treats local pain’.
Claim 21 recites ‘a composition for treating post-surgical pain’, but the specification does not further distinguish the pain to be a local pain. Post-surgical pain is disclosed at para. [003], [012], [0053], [0103], [0123] and Example 3, para. [0150] and local anesthesia is disclosed at para. [048], however the fact that the pain is specific to ‘local pain’ is not disclosed.
M.P.E.P. §2163 states that new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement.
Thus, the disclosure does not provide support for the claim amendments by changing the scope of the disclosure; thereby, constituting new matter.
The remaining claims are rejected as depending from a rejected claim.
Response to Arguments
Applicants argue: "[T]he claimed subject matter need not be described in haec verba in the specification in order for that specification to satisfy the description requirement. In re Wright, 866 F.2d 422, 425 (Fed. Cir. 1989), quoting Application of Smith, 481 F.2d 910, 914 (C.C.P.A 1973). The Specification is directed to compositions that elute active pharmaceutical agents in a way that maintains high local concentrations while minimizing systemic concentrations. For example, paragraph [0150] describes the elution of ropivacaine HCl in a manner that maintains a high local concentration of the ropivacaine HCl. Those of skill in the art would readily understand that a high local concentration of ropivacaine, or any other anesthetic agent, would treat local pain. Further, paragraph [083] describes the treatment of a "desired tissue site" with the disclosed composition, so that an anesthetic agent would "elute from the drug product into the surrounding tissue."
Applicant’s arguments have been fully considered but they are not persuasive, because post-surgical pain involves a narrower scope of invention in contrast to the broader claim of ‘local pain’. The statements: ‘The Specification is directed to compositions that elute active pharmaceutical agents in a way that maintains high local concentrations while minimizing systemic concentrations. For example, ‘paragraph [0150] describes the elution of ropivacaine HCl in a manner that maintains a high local concentration of the ropivacaine HCl’ and/or ‘paragraph [083] describes the treatment of a "desired tissue site" with the disclosed composition, so that an anesthetic agent would elute from the drug product into the surrounding tissue’, does not provide sufficient information to provide support for all forms of local pain. Moreover, there are no specific examples in the disclosure specifically directed to local pain, e.g., pain from a cut or chronic joint pain, etc,). Therefore, the rejection is maintained.
New Grounds of Rejection
Claim Rejections - 35 USC § 103
(Reformulated)
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 2, 5-7, 9, 10, 15 and 17-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Quart et al (US 2020/0078363, cited in IDS filed 5/30/2023) in view of Beloqui et al (Nanostructured lipid carriers: Promising drug delivery systems for future clinics, 12 (2016) p.143), Taylor et al (U 20190175495, cited in IDS filed 5/30/2023), Mulvahill (US 2015/0359738, of record) and Rabinow et al (US20150024031).
Regarding claims 1, 2, 5-7, 9, 10 and 17-20,
Quart teaches compositions and methods for treating post-surgical pain in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a pain medication and a NK-1 receptor antagonist (Abstract; para. [0042]; See entire document). Quart teaches a sustained release delivery vehicle is a microsphere composition, wherein the sustained release delivery is not a liposomal composition (para. [0042]; [0043]; [0367]; [0433]).
Quart teaches administering to a patient in need of postsurgical pain treatment a composition comprising: an aqueous carrier para. [0361) (i.e., an aqueous carrier phase) and a lipid phase comprising an anesthetic agent para. [0051], wherein a lipid-based formulation having anesthetic that is entrapped (i.e., unbound) in the lipid layer (i.e., lipid phase) (para. [0051]; [0071]), wherein a lipid-based delivery vehicle comprising phospholipids such that the phospholipids comprise fatty acyl side chains, for example, the phospholipids comprise a mixture of stearic acid and oleic acid (i.e., elected species), wherein the phospholipids are at most 20 wt% (para. [0142}, i.e., aqueous carrier phase would be about 80 wt%, thus, about 80:20 ratio of aqueous phase:phospholipids. such that the lipid based can be in the form of an emulsion (i.e., emulsified) (para. [0139-0140]), wherein the lipid-based emulsion comprising phospholipids is provided in the form of microspheres, microparticles or microcapsules (para. [0041]; [0179]; [0187]). Thus, for example, a phospholipid: lysophosphatidylcholine (LPC) is 1.47g/mL (Quarts teaches phospholipids can have any combination of fatty acid as its fatty acyl side chain [0139-0140]) and water (aqueous phase has density of 1 gm/mL (20oC), so that 80 gm of water would provide 80mL of aqueous phase and 20 gm of a lipid phase would be expected to provide a volume of about 14 mL, so that 80 ml (water) and 14 ml of phospholipid would provide a total volume of about 94 mL Accordingly, the total percent amount of phospholipid (14/94) is about 15% by volume and water is about 85% by volume. It would have been well within the purview of one of ordinary skill in art to optimize the amount of water (aqueous phase) to phospholipid phase to at least provide a volumetric ratio of between the aqueous carrier phase and the lipid microparticles is from about 70-80 aqueous carrier phase to about 30-20 lipid microparticles in view of the teachings of Quart having a reasonable expectation of success. Optimization of parameters is a routine practice that would be obvious to a person of ordinary skill in the art to employ and reasonably expect success; See In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). As MPEP 2144.05 recites ‘where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable relative volume ranges by routine optimization. Moreover, the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to determine the optimum range for the volume percentage amounts. A prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).
In addition, Beloqui teaches that nanostructured lipid carriers comprising an unstructured solid lipid matrix made of a mixture of blended solid and liquid lipids and an aqueous phase typically, has solid lipids that are mixed with liquid lipids in a ratio of 70:30 up to a ratio of 99.9:0.1 (p.144, left col: NCL formulation), of which overlaps with the calimed amount of a ratio of 90:10. Thus, it be prima facie obvious to provide a phospholipid ratio of stearic acid and oleic acid in a ratio of 90:10.
Furthermore, Quart teaches wherein the emulsion is two immiscible liquids in the form of droplets, whose diameter is between 10 nanometers (nm) to 100 microns (µm) (para. [0133]; wherein intervening values are encompassed by range), wherein anesthetic is present as a salt base (i.e., dissolved in aqueous phase), wherein the release of the anesthetic is at 37oC (para. [0048]), wherein the composition comprises a wax para. [0138], resulting in a sustained-release delivery of an anesthetic. Moreover, Quart teaches that the pain medication (anesthetic) is ropivacaine (para. [0015]; [0017]; [0320]; [0386]) (ropivacaine is recited in instant claim 19); See entire document). Quart teaches the anesthetic is present in 1 wt% to 30 wt% (para. [0321]), of which overlaps with the claimed amount (Instant Claim 20). 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, 91 9 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Therefore, it would have been obvious to one of ordinary in the art before the effective filing date of the claimed invention to provide a composition for treating post-surgical pain in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a pain medication and a NK-1 receptor antagonist (Abstract; para. [0042]; See entire document), wherein the sustained release delivery vehicle is lipid microparticles dispersed in an aqueous carrier phase, wherein the lipid microparticles are not liposomes in accordance with the teachings of Quart.
Quarts differs from the claims in that the document does not teach the that aqueous carrier phase is a hydrogel comprised of tyramine substituted hyaluronic acid, wherein the hydrogel is formed through di-tyramine crosslinking and wherein the degree of tyramine substitution of hyaluronic acid hydroxyl groups is about 0.5% to about 3%, wherein the hydrogel comprising an aqueous carrier phase further comprises a mixture of stearic acid and oleic acid,
However, Taylor and Mulvahill, as a whole, cure the deficiencies.
Taylor teaches a hydrogel-based biological delivery vehicle used to effectively deliver a drug, wherein a hydrogel binding matrix comprises a biopolymer backbone containing carboxyl groups, wherein Tyramine is substituted for at least a portion of the carboxyl groups, wherein examples of biopolymer backbone include sodium hyaluronate. The carboxy groups may be reacted with tyramine to create 0.5% to 5.0% substitution of the carboxyl groups with tyramine molecules, but could theoretically be created at lower or higher substitutions, wherein the percentage of substitution indicates the percent of tyramine substitutions made in relation to the number of carboxyl groups available to be substituted. In addition to a desired substitution rate, preferred embodiments of the hydrogel matrix have a desired THA (Tyramine) concentration. Particularly, the binding matrix are comprised of 1.0-5.0% concentration of THA (i.e., 1.0-5.0% THA in water) with tyramine substitutions at or below 1.5%. (para. [0043]). In particular, Taylor teaches that when hydrogen peroxide is added, it causes creation of covalent bonds between tyramine molecules and cross-links the hydrogel binding matrix, thereby enabling the hydrogel binding matrix to transition from liquid to gel state, wherein the hydrogel binding matrix, in its liquid form, is capable of encapsulating drug reservoirs to create a homogenous liquid with evenly distributed particles containing drugs or target molecules, wherein the hydrogel binding matrix solidifies into a gel state, the newly created cross-links do not disrupt or react with the drugs or target molecules contained within the drug reservoirs, so that the hydrogel-based biological delivery vehicle can be used in several medical applications. (Abstract; See entire document). Moreover, Taylor teaches a solution that enables a hydrogel to cross-link without creating residual material, that promotes higher level of drug/medication concentration loading, that does not react with or deactivate drugs/medications loaded into the hydrogel, and that enables drug delivery vehicles, also referred to as drug reservoirs, to have more stability and to release at a predictable rate in a desired location [0004-0005]; [0023]; See entire document). Summarily, Taylor teaches a hydrogel matrix comprised of a biopolymer backbone of hyaluronic acid containing tyramine substituents wherein via oxidation of the phenol moiety thereof via radical polymerization the tyramine groups are crosslinked to provide a matrix wherein the homogenous liquid phase particles are evenly distributed, for example, medication.
One skilled in the art would have been motivated to modify the composition comprising an aqueous carrier phase having lipid microparticles comprising ropivacaine (anesthetic agent) dispersed within the aqueous carrier phase, wherein the lipid microparticles are not liposomes, so that the aqueous carrier phase is a hydrogel delivery vehicle used to deliver ropivacaine in a controlled manner in order to extend the duration of the anesthesia effect ropivacaine having a reasonable expectation of success, wherein one of ordinary skill in the art before the effective filing date of the claimed invention would have recognized that controlled release of ropivacaine would be expected to reduce systemic toxicity by minimizing and/or alleviating a sudden burst of ropivacaine concentration to patient, wherein the hydrogel comprises a sodium hyaluronate backbone containing carboxyl groups, wherein tyramine is substituted for at least a portion of the carboxyl groups so that when the hydrogel is in liquid form it capable of encapsulating drug reservoirs to create a homogenous liquid with evenly distributed microparticles, e.g., lipid microparticles, containing a drug, e.g., ropivacaine, such that when the hydrogel delivery vehicle is in a gel state, the newly created tyramine cross-links do not disrupt or react with the drug contained within the drug reservoirs in accordance with teachings of Taylor.
Mulvahill teaches a mucosa absorption enhancer (e.g., a fatty acid, a mixture of stearic acid and oleic acid (elected species), such that when added to a pharmaceutical composition can increase the absorption of a therapeutic agent (e.g., a local anesthetic agent in its free-base form) and/or drug delivery vehicle (e.g., any of the drug delivery vehicles), for example, a drug delivery vehicle that includes an entrapped and/or encapsulated local anesthetic agent in its free-base form.
Accordingly, it would have been obvious to those skilled in the art to include a fatty acid (e.g., a mixture of stearic acid and oleic acid) in the lipid microparticles to increase absorption of ropivacaine (anesthetic) at the surgical site to enhance the effectiveness of the anesthetic to treat the post-surgical pain having reasonable expectation of success.
Quarts, Taylor and Mulvahill differ from the claims in that the documents do not teach that ropivacaine (anesthetic agent) is used to treat local pain.
However, Rabinow cures the deficiency
Rabinow explicitly teaches that ropivacaine is used to treat local pain, wherein ropivacaine improved pain relief, reduced morphine consumption and accelerated postoperative recovery (i.e., post-surgical). Moreover, Rabinow teaches the administration of microparticles of a local anesthetic agent such as ropivacaine beneficially reduces pain, inflammation, and/or immunological reactions, such as those associated with parenteral administration of a therapeutic agent (para. [0031]). Rabinow teaches that ropivacaine provided as a ropivacaine salt, a ropivacaine prodrug, a ropivacaine analog, a ropivacaine derivative, or a combination thereof [0071]. Moreover, Rabinow teaches ropivacaine provided in the form of a microparticle in a sustained release formulation is safe, wherein the microparticles have a particle size of less than 20 micrometers (para. [0088]-[0101]; claims 1-12). Rabinow that microparticles of ropivacaine can be delivered via injection, for example, by intraarticular, intracerebral (intraparenchymal), intracerebroventricular, intracerebrospinal, intracranial, intramuscular, intradermal, intraperitoneal, subcutaneous, intraocular, intraportal, intranasal, or intralesional routes (para. [0073]. Further, Rabinow teaches
ropivacaine is surprisingly more effective than celecoxib (para, [0104].
Accordingly, one of ordinary skill in the art would have recognized the many benefits of using ropivacaine to treat local pain in view of the Rabinow for at least the reasons that it improves pain relief, reduced morphine consumption and accelerated postoperative recovery and is surprisingly more effective than celecoxib.
Regarding claim 15,
Claim 15 recites: the composition of claim 1, wherein the plurality of lipid microparticles comprises a first plurality of lipid microparticles and a second plurality of lipid microparticles and wherein the first plurality of lipid microparticles is solid at about 37°C and the second plurality of lipid microparticles is liquid at 37°C.
As discussed above, Mulvahill teaches a mucosa absorption enhancer, e.g., a fatty acid, a mixture of stearic acid and oleic acid (elected species).
It would necessarily follow that a first plurality of liquid microparticles comprising stearic acid would be a solid at about 37°C and a second plurality of liquid microparticles comprising oleic acid would be a liquid at about 37°C.
This reasoning is based on the facts that a compound cannot be separated from its properties. Products of identical chemical composition cannot have mutually exclusive properties. 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. See MPEP 2112. 01 II.
Thus, it would have been obvious for one of ordinary skill in the art to provide instantly claimed invention and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by Quart, Taylor and Mulvahil, as a whole.
All the claimed elements herein are 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 would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Thus, it would have been obvious for one of ordinary skill in the art to provide instantly claimed invention and one of ordinary skill would have had a reasonable expectation of success in producing the claimed invention. Therefore, in the absence of evidence to the contrary, the invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by Quart, Taylor, Mulvahill and Rabinow, as a whole.
New Grounds of Rejection
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 1-6 and 8-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, 9, 10, 15, 16 19 and 20 of copending Application No. 18/109028 (herein ‘028).
Although the claims at issue are not identical, they are not patentably distinct from each other because Instant Claims and ‘213 claim share common subject matter.
Instant Claims are directed to a composition for treating post-surgical pain comprising an aqueous carrier phase; and a lipid phase comprising an anesthetic agent, the lipid phase dispersed within the aqueous carrier phase and wherein lipid phase comprises a plurality of lipid microparticles, [wherein the lipid microparticles are not liposomes, and wherein the volumetric ratio between the aqueous carrier phase and the lipid microparticles is from about 70-80 aqueous carrier phase to about 30-20 lipid microparticles; wherein the lipid microparticles comprise one or more fatty acids having an even number of carbons; wherein the one or more fatty acids are chosen from: stearic acid, oleic acid, myristic acid, caprylic acid, capric acid, lauric acid, palmitic acid, arachidic acid, lignoceric acid, cerotic acid, and mixtures of the forgoing and wherein the melting point of the lipid microparticle is above 37°C; wherein the one or more fatty acids comprise a mixture of steric acid and oleic acid and wherein the ratio of steric acid to oleic acid is about 90:1; wherein the plurality of lipid microparticles comprises a first plurality of lipid microparticles and a second plurality of lipid microparticles and wherein the first plurality of lipid microparticles is solid at about 37°C and the second plurality of lipid microparticles is liquid at 37°C; wherein the lipid microparticle ranges in size from about 1 μm to about 20 μm.
‘028 claims are directed to a composition for treating cancer comprising an aqueous carrier, wherein the aqueous carrier is hydrogel comprised of tyramine substituted hyaluronic acid, wherein the hydrogel is formed through di-tyramine crosslinking and wherein the degree of tyramine substitution of hyaluronic acid hydroxyl groups is about 0.5% to about 3%.; and a lipid phase comprising an antitumor agent, the lipid phase dispersed within the aqueous carrier, wherein the lipid phase comprises a plurality of lipid microparticles, wherein the volumetric ratio between the aqueous carrier and the lipid microparticles is from about 70-80 the aqueous carrier to about 30-20 lipid microparticles; wherein the one or more fatty acids are chosen from: stearic acid, oleic acid, myristic acid, caprylic acid, capric acid, lauric acid, palmitic acid, arachidic acid, lignoceric acid, cerotic acid, and mixtures of the forgoing and wherein the melting point of the lipid microparticle is above 37°C; wherein the lipid microparticle is not a liposome; wherein the plurality of lipid microparticles range from about 5 μm to about 20 μm.
Thus, Instant Claims and ‘028 claims are obviously directed to common subject matter, since they both claim a method for intranasal administration of a dry powder pharmaceutical composition comprising intranasally administering a single dose of a dry powder pharmaceutical composition comprising epinephrine or a pharmaceutically acceptable salt thereof.
Accordingly, it would have been prima facie obvious to one of skill in the art to provide the method for intranasal administration of a dry powder pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘028 claims before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicants argue that no reasoning is given why a person of ordinary skill in the art would be motivated to intersperse the lipid microparticles as taught by Quart, in the hydrogel matrix described by Taylor.
Applicant’s arguments have been fully considered but they are not persuasive, because one of ordinary skill in the art before the effective filing date of the claimed invention would have expected to provide controlled release such that the lipid phase comprising ropivacaine would extend the duration of its anesthesia having a reasonable expectation of success such that controlled release of ropivacaine would reduce systemic toxicity by minimizing and/or alleviating a sudden burst of ropivacaine concentration at the delivery location of ropivacaine in a patient in need thereof. Moreover, Rabinow teaches ropivacaine provided in the form of a microparticle in a sustained release formulation is safe. Furthermore, the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (In re Kahn, 78 USPQ2d 1329, 1336, Federal Circuit 2006). See MPEP § 2144, IV. Rationale Different from Applicant's is Permissible.
Applicants argue that claim 1 has been amended to recite the limitation "wherein the volumetric ratio between the aqueous carrier phase and the lipid microparticles is from about 70-80 aqueous carrier phase to about 30-20 lipid microparticles. Applicants argue that Quart is cited as disclosing a ratio of lipid microparticles to aqueous carrier phase of 20% to 80%. The cited section of Quart is paragraph [0142], which recites "The amount of phospholipids, by weight, in the emulsions of the present disclosure may be within a range of about 10 wt/wt% to about 20 wt/wt%, 11 wt/wt% to 19 wt/wt%, 11 wt/wt
% to 15 wt/wt%, 12 wt/wt% to 13 wt/wt%, 13 wt/wt% to 14 wt/wt%, 13 wt/wt% to 20 wt/wt %, or 12 wt/wt% to 18 wt/wt%." There are several issues with relying on Quart for this limitation. First, these are not volumetric ratios, as presently claimed. Rather, these are weight percentages. Second, the Office Action assumes that a formulation with 20 wt/wt% of phospholipids would then have 80% aqueous carrier phase, but this ignores the presence of any active pharmaceutical ingredients. This is a key difference between a weight percent and a ratio between two ingredients. Finally, Quart gives no motivation for why the 20 wt/wt% should be selected from this generic list and combined with the other pieces of prior art.
Applicant’s arguments have been fully considered but they are not persuasive, because the limitation: the volumetric ratio between the aqueous carrier phase and the lipid microparticles is from about 70-80 aqueous carrier phase to about 30-20 lipid microparticles, would have been obvious in view of the teachings of Quart, because the amounts of 80% water and 20% wt would be expected to encompass these claimed features, especially in view of the illustrative example as provided above. Moreover, it would be prima facie obvious to provide lipid microparticles having a ratio stearic and oleic acid ratio in view of the teachings of Beloqui, as described above.
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981
The PTO can require an applicant to establish that a prior art product does not necessarily possess the characteristics of the claimed product, e.g., 95% ethanol, when the prior art and claimed products are identical or substantially identical. An applicant's burden under these circumstances was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433-434 (CCPA 1977) as follows: Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on 'inherency' under 35 U.S.C. § 102, or 'prima facie obviousness' under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products.
Furthermore, though picked from a "laundry list", it has been held that though a specific embodiment is not taught as preferred makes it no less obvious, also, the mere fact that a reference suggests a multitude of possible combinations does not in and of itself make any one of those combinations less obvious, see Merck v. Biocraft, 10 USPQ2d 1843 (Fed Cir 1985). It is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. BiocrafiLabs, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).
Applicants argue that the Office Action assumes that a formulation with 20 wt/wt% of phospholipids would then have 80% aqueous carrier phase, but this ignores the presence of any active pharmaceutical ingredients. However, this not persuasive, because Quart teaches the anesthetic can be present in the microsphere composition at 1 wt%, where this would not be expected to substantially have a dramatic effect on the concentration of each ingredient, as a whole. Moreover, instant claims do not claim a wt% amount of the anesthetic agent, so that the prior art of Quart, even as low of 1 wt% of anesthetic agent, does not teach away from the claimed invention. Furthermore, the test for obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Moreover, obviousness does not require absolute predictability, however, at least some degree of predictability is required. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976).
Conclusions
No claim is allowed.
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/THURMAN WHEELER/ Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619