CTNF 18/034,649 CTNF 99948 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority 02-09 AIA Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: 02-10 AIA The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc. , 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application, Application No. 63/108,072 , fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicates a lack of support for metformin in claim 25 in the PRO application. Thus a priority date of 11/01/2021 was used for claim 25. The remaining claims were given a priority date of 10/30/2020 . Information Disclosure Statement The information disclosure statements (IDS) submitted on 04/28/2023 and 12/11/2024 are being considered by the examiner. 07-30-03-h AIA Claim Interpretation Claim 27 has been interpretation as an improper process claim because the applicants have defined [0048] a pharmaceutical formulation as a process. Claim Objections 07-29-01 AIA Claim 20 is objected to because of the following informalities: there are two little white boxes instead of the alpha symbol . Appropriate correction is required. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claim 27 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 27 provide for the use of a pharmaceutical formulation, but, since the claims do not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. A pharmaceutical formulation is a process of making the composition but no steps are given for the process and no steps are given for the use of this process in the method of claim 1. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claim 27 is rejected under 35 U.S.C. 101 because it claims recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki , 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. v. Brenner , 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966). Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-15-aia AIA Claim(s) 1, 2, 6, 9, 10 and 27 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Chappell (Chappell et al., US-20070225217-A1, 2007-09-27) . The reference Chappell teaches a method of reducing progression of an inflammatory disease, “ The invention features compositions, methods, and kits for the treatment of immunoinflammatory disorders and ophthalmic disorders”[0015] and “In a related aspect, the invention features a method of modulating an immune response (e.g., by decreasing proinflammatory cytokine secretion or production, or by modulating adhesion, gene expression, chemokine secretion, presentation of MHC complex, presentation of costimulation signals, or cell surface expression of other mediators) in a patient by administering to the patient a drug pair selected from the pairs listed on Table 1A simultaneously or within 14 days of each other in amounts sufficient to modulate the immune response in the patient”[0019]. PNG media_image1.png 365 487 media_image1.png Greyscale The reference Chappell teaches the specific combination of drugs as listed in Table 1A (shown below). This anticipates claims 1, 6 and 27. The reference Chappell teaches “ The invention also features a method for treating a musculoskeletal disorder, e.g., osteoarthritis , by administering to a patient diagnosed with or at risk of developing such a disorder a drug pair selected from the pairs listed on Table 1A, such that the two drugs are administered simultaneously or within fourteen days, ten days, five days, or even 24 hours of each other in amounts sufficient to treat the patient ” [0032]. This anticipates claims 2, 9 and 10 . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim (s) 1, 2, 4, 5, 6, 9, 10, 11, 13, 14, 24, 26, 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chappell (Chappell et al., US-20070225217-A1, 2007-09-27) . The reference Chappell teaches a method of reducing progression of an inflammatory disease, “ The invention features compositions, methods, and kits for the treatment of immunoinflammatory disorders and ophthalmic disorders”[0015] and “ Loratadine (CLARITIN) is a tricyclic piperidine that acts as a selective peripheral histamine H1-receptor antagonist . Loratadine and structural and functional analogs thereof, such as piperidines, tricyclic piperidines, histamine H1-receptor antagonists, may be used in the anti-immunoinflammatory combination of the invention for the treatment of immunoinflammatory disorders , transplanted organ rejection, and graft versus host disease”[0238]. This helps to teach claims 1, 6 and 27. The reference Chappell teaches combinations that “Desirably, one or both drugs are present in amounts that together are sufficient to treat an immunoinflammatory disorder, ophthalmic disorder, or musculoskeletal disorder, or pain, tenderness, impairment in mobility, soft tissue swelling, or bony swelling associated therewith in a patient in need thereof. Exemplary drug pairs are: antihistamine and phosphodiesterase inhibitor; antihistamine and SSRI ; antihistamine and tricyclic compound ; antinfective and anticoccidial compound; corticosteroid and antihistamine …”[0016] and “By " corticosteroid " is meant any naturally occurring or synthetic compound characterized by a hydrogenated cyclopentanoperhydro-phenanthrene ring system and having immunosuppressive and/or anti-inflammatory activity. Naturally occurring corticosteroids are generally produced by the adrenal cortex. Synthetic corticosteroids may be halogenated. Examples corticosteroids are provided herein”[0067]. Additionally, the reference teaches “ Particularly desirable antihistamines for use in the methods, compositions, and kits of the invention are non-sedating antihistamines such as loratadine and desloratadine”[0230]. This helps to teach claims 1, 24 and 26. PNG media_image1.png 365 487 media_image1.png Greyscale The reference Chappell teaches the specific combination of drugs as listed in Table 1A (shown below). The reference Chappell teaches “ The invention also features a method for treating a musculoskeletal disorder, e.g., osteoarthritis , by administering to a patient diagnosed with or at risk of developing such a disorder a drug pair selected from the pairs listed on Table 1A, such that the two drugs are administered simultaneously or within fourteen days, ten days, five days, or even 24 hours of each other in amounts sufficient to treat the patient ” [0032]. This helps to teach claims 2, 9, 10. The reference Chappell teaches “Each compound of the combination may be formulated in a variety of ways that are known in the art. For example, the first and second agents may be formulated together or separately. Desirably, the first and second agents are formulated together for the simultaneous or near simultaneous administration of the agents. Such co-formulated compositions can include the two drugs together in the same pill, ointment, cream, foam, capsule, liquid, et c”[0279]. This helps to teach claim 11. The reference Chappell teaches “ Structural analogs of antihistamines may also be used in according to the invention. Antihistamine analogs include, without limitation … rupatadine …” [0232]. Since rupatadine is a platelet activating factor inflammatory lipid receptor antagonist independent if the property was known at the time. “Products of identical chemical composition cannot have mutually exclusive properties.” Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F. 2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).This helps to teach claim 4, 5, 26. The reference Chappell teaches “As described above , the compound in question may be administered orally in the form of tablets, capsules, elixirs or syrups, or rectally in the form of suppositories” [0300]. This helps to teach claim 13. The reference Chappell teaches “ The methods, compositions, and kits of the invention may be used for the treatment of osteoarthritis, or pain, tenderness, impairment in mobility, soft tissue swelling, or bony swelling associated therewith . If desired, one or more agents typically used to treat osteoarthritis may be used as a substitute for or in addition to a corticosteroid in the methods, compositions, and kits of the invention. Such agents include NSAIDs (e.g., naproxen sodium, diclofenac sodium, diclofenac potassium , aspirin , sulindac, diflunisal, piroxicam, indomethacin, ibuprofen , nabumetone, choline magnesium trisalicylate, sodium salicylate, salicylsalicylic acid (salsalate), fenoprofen, flurbiprofen, ketoprofen, meclofenamate sodium, meloxicam, oxaprozin, sulindac, and tolmetin), COX-2 inhibitors (e.g., rofecoxib, celecoxib, valdecoxib, and lumiracoxib …”[0271]. This helps to teach claims 1 and 14. The reference Chappell teaches “By "selective serotonin reuptake inhibitor" or "SSRI" is meant any member of the class of compounds that (i) inhibit the uptake of serotonin by neurons of the central nervous system, (ii) have an inhibition constant (Ki) of 10 nM or less, and (iii) a selectivity for serotonin over norepinephrine (i.e., the ratio of Ki(norepinephrine) over Ki(serotonin)) of greater than 100. Typically, SSRIs are administered in dosages of greater than 10 mg per day when used as antidepressants. Exemplary SSRIs for use in the invention are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and venlafaxine” [0080]. This helps to teach claim 24. The reference Chappell does not specifically teach the combination for the instant claims and instead requires picking and choosing of several variables. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Chappell to get the instant invention because Chappell teaches all the correct drugs for treating the correct condition and suggests their combination. Thus it would have been obvious to combine them with a reasonable expectation of success because they are performing the same function as they have been known to perform and yield no more than one would expect. One would be motivated to combine them because such combinations are suggested by Chappell to treat inflammation. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742 . 07-21-aia AIA Claim (s) 1, 2, 4, 5, 6, 7, 14 and 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over LEIGHTON (LEIGHTON et al., US 2015374703 A1, 2015-12-31) . The reference LEIGHTON teaches “ The present invention relates to compositions containing a combination of a stimulant and an anti-histamine compounds, to methods for treating symptoms related to inflammation using the combination compounds , and to a method for preparing the compositions ”[0002] and “ In some embodiments, the composition of the present invention is used to treat symptoms associated or related to inflammation. As used herein, “treating,” “treat” or “treatment” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition, protecting from harmful or annoying stimuli, or generally promoting health.”[0042]. This helps to teach claims 1 and 27. The reference LEIGHTON teaches “ It now has been found that compositions comprising at least one stimulant such as a methyl xanthine and at least one anti-histamine such as an H1 receptor antagonist or reverse agonist to provide unexpected degrees of improvement of symptoms associated with inflammation over the effects of either compound alone . Without being bound by any particular theory, the treatment of symptoms related to or associated with inflammation can be the unexpected or synergistic result of the ability of the combination of stimulant and anti-histamine compounds to modulate the effects of one or more of TNF-α, IL-1β, IL-12, and IL-10, and/or pathways associated therewith. The present invention, therefore, is directed to compositions and uses of stimulant and anti-histamine compounds for treating symptoms associated with inflammation , and for other unmet needs” [0005] and “The body's response to inflammation can include various symptoms, including edema, vasodilation, fever and pain , amongst others” [0056] This helps to teach claim 1 and 7. The reference LEIGHTON teaches “In preferred embodiments, the stimulant is a methyl xanthine optionally as caffeine or a derivative and the anti-histamine is a histamine-1 (H1) receptor antagonist or reverse agonist , selected from loratadine , fexofenadine, levocetirizine dihydrochloride, 4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-ylbut-2-enyloxy)acetic acid, and/or cetirizine”[0026]. This helps to teach claims 1, 6 and 26. The reference LEIGHTON teaches “ Inflammation can result from a wide variety of diseases, conditions, syndromes, disorders, injuries and the like of the various anatomical systems, including, and without limitation , those of the: [0049] (1) skeletal system including, but not limited to, such diseases, conditions, syndromes, disorders, and injuries, such as (a) arthritis, including, but not limited to , psoriatic arthritis, osteoarthritis, rheumatoid arthritis , juvenile rheumatoid arthritis, juvenile psoriatic arthritis, and Gouty arthritis…”[0048-0049]. This helps to teach claim 2. The reference LEIGHTON teaches “[0041] In one aspect, the present invention provides compositions having a stimulant and anti-histamine, H1 receptor antagonist, or H1 receptor reverse agonist compound, for example and without limitation, the stimulant is caffeine or a derivative and the anti-histamine, H1 receptor antagonist, or H1 receptor reverse agonist is selected from loratadine , fexofenadine, levocetirizine dihydrochloride, and 4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-ylbut-2-enyloxy)acetic acid (SUN-1334H), and/or cetirizine (hereinafter, “C/L,F, LD, SUN or C”) for treating, or preventing, inflammation, or for promoting overall health of the various anatomical systems and their related joints, tissues, and organs… Non-limiting examples of H1 receptor antagonists or reverse agonists useful in the present invention can optionally include one or more … rupatadine …”[0041]. Since rupatadine is a platelet activating factor inflammatory lipid receptor antagonist independent if the property was known at the time. “Products of identical chemical composition cannot have mutually exclusive properties.” Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F. 2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).This helps to teach claims 4 and 5. The reference LEIGHTON teaches “The specificity of coxibs allows these NSAIDs to reduce inflammation with minimal gastrointestinal side effects, such as dyspepsia, ulcer perforation, and upper gastrointestinal bleeding that are common with NSAIDs that act on both COX genes. Studies, however, have demonstrated an increased risk of cardiovascular events associated with the use of the coxibs celecoxib, valdecoxib and parecoxib than with other NSAIDs ”[0129]. This helps too teach claim 14. The reference LEIGHTON does not specifically teach the combination for the instant claims and instead requires picking and choosing of several variables. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified LEIGHTON to get the instant invention because LEIGHTON teaches all the correct drugs for treating the correct condition and suggests their combination. Thus it would have been obvious to combine them with a reasonable expectation of success because they are performing the same function as they have been known to perform and yield no more than one would expect. One would be motivated to combine them because such combinations are suggested by LEIGHTON to treat inflammation. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742 . 07-21-aia AIA Claim (s) 1, 2, 4, 5, 6, 7, 14, 16, 17 and 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over LEIGHTON (LEIGHTON et al., US 2015374703 A1, 2015-12-31) and over Chappell (Chappell et al., US-20070225217-A1, 2007-09-27) in view of CHU (CHU et al., CN 108003139 A, 2018- 05-08) and FDA(FDA, CELEBREX ® (celecoxib) capsules, for oral use, 6/2018) and further in view of KARAAĞAÇ(KARAAĞAÇ et al., TR-201412739-A, 05/23/2016) . The LEIGHTON and Chappell have been discussed supra and do not disclose the amounts in mg of claims 16 and 17. The reference CHU teaches “ This invention relates to the technical field of biological medicine, specifically claims a rupatadine fumarate compound crystal and tablet … rupatadine fumarate (Rupatadinefumarate) is a histamine H1 receptor and platelet activating factor receptor intellectural with new antiallergic agents, can act a link different from allergic reaction to occur so as to inhibit an inflammatory response . The medicine is comprised of Spanish Uriah pharmaceutical companies developing market in Spanish to 2003 3, firstly, the approval indication is seasonal and perennial allergic rhinitis. research shows that the double function of rupatadine with antihistamine and anti-PAF, histamine antagonists with other similar or has stronger antihistamine activity and has anti-PAF . allergic disease is a multifactorial disease complex, with multiple medium-mediated inflammation. antigenic stimulation the mast and basophil cells release histamine cause inflammatory response early. PAF is another important inflammatory factor, is an important medium of late allergic reaction . histamine and PAF are complementary , and promotes the release of each other in different tissues and cells. so the rupatadine fumarate is expected to become the line medicine for treating allergic rhinitis and allergic urticaria. At present, the market in overseas of rupatadine fumarate preparation is tablet, specification is 10 mg. tablet with convenient taking and carrying, low cost, easy industrial production and so on. However, the existing rupatadine fumarate tablet is bare, the surface is rough, the moisture-proof, light, abrasion resistance performance is bad, easy to generate fragments or damped make it difficult to disintegration, dissolution and bioavailability reduces the effective period, a drug store. at the same time, the rupatadine fumarate bitter taste, difficult and not convenient for child patient to swallow”[0002-0006]. This helps to teach claim 16. The reference FDA teaches “ CELEBREX (celecoxib) capsule is a nonsteroidal anti-inflammatory drug , available as capsules containing 50 mg , 100 mg , 200 mg and 400 mg celecoxib for oral administration ”(section 11). This helps to teach claims 16 and 17. The reference KARAAĞAÇ teaches “The dosage range of the formulations suitable for pharmaceutical compositions in which the active ingredients of the present invention are used in combination; For montelukast and / or pharmaceutically acceptable derivatives, from 1 to 30 mg, preferably from 4 mg, 5 mg, 8 mg, 10 mg; For rupatadine and / or pharmaceutically acceptable derivatives, from 1 to 40 mg is preferably 4 mg, 5 mg, 8 mg , 10 mg , 12 mg, adjusted according to the individual needs of the patient and the judgment of the expert”(translated pages 6-7). This helps to teach claim 16 and 17. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified LEIGHTON and Chappell which both teach histamine H1 receptor rupatadine and celecoxib for the treatment of inflammation with CHU, FDA and KARAAĞAÇ because they all provide common dosage amounts for treatment with either rupatadine and celecoxib. It would have been obvious and one would be motivated to use these amounts because they have proven to be non-hazardous amounts that work for treatment and they are in some cases already commercially available in that amount which provides an ease of access. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.) 07-21-aia AIA Claim (s) 1, 18 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ma (Ma et al., WO-2013049621-A1, 2013-04-04) . The reference Ma teaches “ Preferred Composition: The ophthalmic composition comprises PPAR- alpha agonist(s) (0.0001-95, preferably 1-10)%; and further comprises additive, lipid(s) and delivery agent(s) that assists in penetration of surface of the eye or delivery to cornea or retina of the eye. The ophthalmic composition comprises an emulsion. The pharmaceutical composition further comprises a second therapeutic agent. Preferred Component: The PPAR- alpha agonist is fenofibrate. The additive is glycerin, castor oil, soybean lecithin, polyoxyethylene-polyoxypropylene block copolymer, alpha -tocopherol and/or carboxymethyl cellulose. The second therapeutic agent is an anti-angiogenic agent and/or an anti-vascular endothelial growth factor reagent. The second therapeutic agent is … ZADITOR (RTM: ketotifen).. .”(pages 5-6) and “ Therefore, there exists a need for new and improved compositions containing PPARa agonists , s uch as, but not limited to, fenofibrate, a s well as methods of production and use thereof . Such compositions and methods would be useful in the treatment and prevention of neovascularization-associated and/or Wnt signaling pathway associated diseases, including but not limited to, inflammation , fibrosis, angiogenesis and/ortumorigenesis. The present disclosure is directed to compositions and methods, which overcome the disadvantages and defects of the prior art”(page 4). This helps to teach claims 1, 18, and 20. The reference Ma does not specifically teach the combination for the instant claims and instead requires picking and choosing of several variables. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Ma to get the instant invention because Ma teaches all the correct drugs for treating the correct condition and suggests their combination. Thus it would have been obvious to combine them with a reasonable expectation of success because they are performing the same function as they have been known to perform and yield no more than one would expect. One would be motivated to combine them because such combinations are suggested by Ma to treat inflammation. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742 . 07-21-aia AIA Claim (s) 1 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over BLISKO (BLISKO et al., WO-2018231829-A1, 2018-12-20) . The reference BLISKO teaches “ One or more additional antipruritic agents can optionally be used in combination with the agent that antagonizes elevated ALP and/or progesterone inhibitors to treat said itch, skin inflammation , or pruritus (including acute and chronic pruritus). Antipruritic agents are well known and are fully described, for example, in U.S. Patent Application 9,381,188, which is incorporated by reference in its entirety. Examples of antipruritic agents include without limitation: antihistamines, including but not limited to antihistamines that inhibit action at the histamine H1 receptor (e.g., acrivastine, antazoline, azelastine, bilastine, brompheniramine, buclizine, bromodiphenhydramine, carbinoxamine, cetirizine, chlorpromazine, cyclizine, chlorpheniramine, chlorodiphenhydramine, clemastine, cyproheptadine, desloratadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, doxepin, doxylamine, ebastine, embramine, fexofenadine, hydroxyzine, levocetirizine, loratadine , … bile absorption-reducing or bile sequestering agents ( e.g., ursodeoxycholic acid [ursodiol ]), ultraviolet radiation (e.g., ultraviolet A and B), and analogs and derivatives thereof”[053]. This helps to teach claims 1 and 22. The reference BLISKO does not specifically teach the combination for the instant claims and instead requires picking and choosing of several variables. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified BLISKO to get the instant invention because BLISKO teaches all the correct drugs for treating the correct condition and suggests their combination. Thus it would have been obvious to combine them with a reasonable expectation of success because they are performing the same function as they have been known to perform and yield no more than one would expect. One would be motivated to combine them because such combinations are suggested by BLISKO to treat inflammation. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742 . 07-21-aia AIA Claim (s) 1, 7, 14 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over BERGERON (BERGERON et al., WO-2007002701-A2, 2007-01-04) . The reference BERGERON teaches “ The compounds of the present invention can be combined with other compounds having related utilities to treat or prevent inflammatory and immune disorders and diseases, including asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis , and those pathologies noted above. In many instances, compositions which include a compound of the invention and an alternative or second therapeutic agent have additive or synergistic effects when administered. [00193] For example, in the treatment or prevention of inflammation, the present compounds may be used in conjunction or combination with an anti-inflammatory … When a compound of the present invention is used contemporaneously with one or more other drugs, a pharmaceutical composition containing such other drugs in addition to the compound of the present invention is preferred. Accordingly, the pharmaceutical compositions of the present invention include those that also contain one or more other active ingredients , in addition to a compound of the present invention. Examples of other active ingredients that may be combined with a compound of the present invention, either administered separately or in the same pharmaceutical compositions, include, but are not limited to… (d) antihistamines (Hl -histamine antagonists) such as bromopheniramine, chlorpheniramine, dexchlorpheniramine, triprolidine, clemastine, diphenhydramine, diphenylpyraline, tripelennamine, hydroxyzine, methdilazine, promethazine, trimeprazine, azatadine, cyproheptadine, antazoline, pheniramine pyrilamine, astemizole, terfenadine, loratadine, cetirizine, fexofenadine , descarboethoxyloratadine, and the like; …(g) cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Celebrex®) … (m) anti-diabetic agents such as insulin, sulfonylureas, biguamides (metformin), … Combinations of a compound of the present invention and other active ingredients will generally also be within the aforementioned range, but in each case, an effective dose of each active ingredient should be used” [00191]. This helps to teach claims 1, 7, 14 and 25. The reference BERGERON does not specifically teach the combination for the instant claims and instead requires picking and choosing of several variables. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified BERGERON to get the instant invention because BERGERON teaches all the correct drugs for treating the correct condition and suggests their combination. Thus it would have been obvious to combine them with a reasonable expectation of success because they are performing the same function as they have been known to perform and yield no more than one would expect. One would be motivated to combine them because such combinations are suggested by BERGERON to treat inflammation. The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Conclusion Claims 1, 2, 4, 5, 6, 7, 9, 10, 11, 13, 14, 16, 17, 18, 20, 22 , 24-27 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /A.A.S./ Examiner, Art Unit 1627 /Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627 Application/Control Number: 18/034,649 Page 2 Art Unit: 1627 Application/Control Number: 18/034,649 Page 3 Art Unit: 1627 Application/Control Number: 18/034,649 Page 4 Art Unit: 1627 Application/Control Number: 18/034,649 Page 5 Art Unit: 1627 Application/Control Number: 18/034,649 Page 6 Art Unit: 1627 Application/Control Number: 18/034,649 Page 7 Art Unit: 1627 Application/Control Number: 18/034,649 Page 8 Art Unit: 1627 Application/Control Number: 18/034,649 Page 9 Art Unit: 1627 Application/Control Number: 18/034,649 Page 10 Art Unit: 1627 Application/Control Number: 18/034,649 Page 11 Art Unit: 1627 Application/Control Number: 18/034,649 Page 12 Art Unit: 1627 Application/Control Number: 18/034,649 Page 13 Art Unit: 1627 Application/Control Number: 18/034,649 Page 14 Art Unit: 1627 Application/Control Number: 18/034,649 Page 15 Art Unit: 1627 Application/Control Number: 18/034,649 Page 16 Art Unit: 1627 Application/Control Number: 18/034,649 Page 17 Art Unit: 1627 Application/Control Number: 18/034,649 Page 18 Art Unit: 1627 Application/Control Number: 18/034,649 Page 19 Art Unit: 1627 Application/Control Number: 18/034,649 Page 20 Art Unit: 1627 Application/Control Number: 18/034,649 Page 21 Art Unit: 1627