Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Reissue: Non-Final Office Action
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. The amendments filed on 7/10/25 have been entered.
Status of the Claims
The amendments and arguments filed Jul. 10, 2025 are acknowledged and have been fully considered. Claims 1-17, 20-23, 27-29, and 37-39 are cancelled; claims 18, 19, 24-26, and 30-36 are new claims relative to US patent 8,569,271. Accordingly, claims 18, 19, 24-26, and 30-36 are now pending and under consideration.
Ongoing Duty To Disclose
Applicant(s) is/are reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which US Patent 8,569,271 is or was involved. These proceedings would include any trial at the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 18, 19, 24-26, and 30-36 remain rejected under 35 U.S.C. 103(a) as being unpatentable over as being unpatentable over Codd (WO 00/51685; Pub. Sep. 8, 2000).
Regarding claim 18, Codd teaches a combination of a tramadol material and a selective COX-2 inhibitor having a synergistic effect useful for treating pain wherein the ratio of tramadol material and COX-2 inhibitor drug is from 1:1 to about 1:300 or from about 1:1 to about 300:1 (entire document, especially, title; abstract; p. 5, lines 25 to p. 6, line 9; p. 16, lines 5-11). Codd teaches that the tramadol material includes racemates of tramadol hydrochloride (p. 6, lines 18-26). Codd teaches that pharmaceutical compositions comprising a combination of tramadol and a selective COX-2 inhibitor drug have a synergistic effect even when using less of each ingredient (p. 5, lines 1-4). Codd teaches celecoxib (Celebrex®) in a small group of possible COX-2 inhibitors (p. 8, lines 3-8; claim 11). Claim 4 which depends from claims 3 and 1 of Codd is directed to a pharmaceutical composition comprising racemic tramadol hydrochloride present in a ratio from about 1:1 to about 1:300 and from about 1:1 to about 300:1 to the COX-2 inhibitor. Furthermore, Codd does not require any other active ingredients in the composition other than a combination of tramadol and a selective COX-2 inhibitor (e.g., celecoxib).
Codd discloses all the limitations of instant claim 18, but fails to exemplify a single embodiment having a combination of racemic tramadol hydrochloride, celecoxib, and one or more pharmaceutically acceptable excipients. However, it would have been obvious to one of ordinary skill in the art at time of the invention to select celecoxib from the small group of COX-2 inhibitors taught because a skilled artisan would be able to readily envision celecoxib from the very limited group of four COX-2 inhibitors disclosed by Codd (p. 8, lines 3-8). In addition, it would have been obvious to the skilled artisan that Codd specifically contemplated celecoxib as a preferred COX-2 inhibitor to be used in combination with the tramadol of claim 1 since it is a claimed embodiment (claim 11).
While the skilled artisan would recognize that a pharmaceutical composition inherently is administered with or contains a pharmaceutically acceptable excipient, Codd teaches that the pharmaceutical composition of claim 1 comprises a pharmaceutically acceptable excipient as the intended function of an excipient is to act as a carrier of the active components (bridging pgs. 9-10). Also, Codd teaches that the carrier depends upon the mode of administration selected (bridging pgs. 9-10). Thus, the limitations of claim 18 are met.
Instant claim 19 requires that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. It would have been obvious to a skilled artisan that claim 11 recites the salt as well as the neutral form of celecoxib because, a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). Further, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field. Thus, Codd meets the limitation of claim 19.
Instant claims 24 and 25 recite that the pharmaceutical composition is in tablet form and is a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26 recites a method of treating pain using the pharmaceutical composition of present claim 18. Codd teaches that one may use their pharmaceutical composition for treating pain (abstract; p. 6, lines 1-9; claims 16, 22 and 23). Thus, the claim limitation is met.
Instant claims 30-32 recite that the pharmaceutical composition is in tablet form, is a single tablet, and is administered up to twice daily, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22) or in multiple doses depending upon the relative amount of each active component being used (p. 10, lines 6-22, especially, lines 11-15 and 19-22). On p. 10, lines 8-11, Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)).
Instant claims 33-35 recite various types of pain (acute, chronic, neuropathic nociceptive, mild, severe, moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, frozen shoulder, and sciatica) for which the racemic tramadol hydrochloride and celecoxib are administered. Codd teaches that the composition is used to treat conditions including osteoarthritis, rheumatoid arthritis, and cancer, as well as various types of pain, including acute, chronic, neuropathic, diabetic peripheral neuropathy, (par. bridging pgs. 10-11; claims 23-26).
Claim 36 recites that the pain is severe to moderate pain. According to MPEP 804.II.B.1, the specification may be used as a dictionary to learn the meaning of a term in the claim. Col. 7, lines 7-8, discloses that severe to moderate pain is that of rheumatoid arthritis, ankylosing spondylitis, sciatica, and frozen shoulder. Thus, it would have been obvious to a skilled artisan at the time the invention was made that the limitation of claims 36 and 39 are met because Codd discloses that the pharmaceutical composition is used to treat rheumatoid arthritis (p. 11, line 5).
Claims 18, 19, 24-26, and 30-36 are rejected under 35 U.S.C. 103(a) as being unpatentable over as being unpatentable over CODD (WO 00/51685; Pub. Sep. 8, 2000) and BURCH (WO 99/13799; Pub. Mar. 25, 1999, on IDS), CHANG (Chang, I. J., et al. Hypertension (Dec. 2004), 45(2); 178-180), YAMAMOTO (Yamamoto, H., et al., Gastroenterology (2003), 125: 556-571), and KOBAYASHI (Kobayashi, H., et al., Int. J. Cancer (2004), 112: 920-926).
Codd teaches a combination of a tramadol material and a selective cyclooxygenase-2 (COX-2) inhibitor having a synergistic effect useful for treating pain wherein the ratio of tramadol material and COX-2 inhibitor drug is from 1:1 to about 1:300 or from about 1:1 to about 300:1 (entire document, especially, title; abstract; p. 5, lines 25 to p. 6, line 9; p. 16, lines 5-11). Codd teaches that the tramadol material includes racemates of tramadol hydrochloride (p. 6, lines 18-26). Codd teaches that pharmaceutical compositions comprising a combination of tramadol and a selective COX-2 inhibitor drug have a synergistic effect even when using less of each ingredient (p. 5, lines 1-4). Codd teaches celecoxib (Celebrex®) in a small Markush grouping of possible COX-2 inhibitors (p. 8, lines 3-8; claim 11). Claim 4 which depends from claims 3 and 1 of Codd is directed to a pharmaceutical composition comprising racemic tramadol hydrochloride present in a ratio from about 1:1 to about 1:300 and from about 1:1 to about 300:1 to the COX-2 inhibitor. Furthermore, Codd does not require any other active ingredients in the composition other than a combination of tramadol and a selective COX-2 inhibitor (e.g., celecoxib).
Codd teaches that the pharmaceutical composition of claim 1 comprises a pharmaceutically acceptable excipient as the intended function of an excipient is to act as a carrier of the active components (bridging pgs. 9-10). Also, Codd teaches that the carrier depends upon the mode of administration selected (bridging pgs. 9-10). Codd teaches a ratio from about 1:1 to about 1:300 and from about 1:1 to about 300:1 of racemic tramadol hydrochloride to celecoxib (p. 5, lines 25 to p. 6, line 9).
Thus, Codd discloses all the limitations of instant claim 18, but fails to exemplify a single embodiment having a combination of racemic tramadol hydrochloride and celecoxib in a molar ratio of about 1:1, along with one or more pharmaceutically acceptable excipients. Thus, the teachings of Codd are not deemed anticipatory. However, it would have been obvious to one of ordinary skill in the art at time of the invention to select celecoxib from the small Markush group because a skilled artisan would be able to readily envision celecoxib from the grouping of four COX-2 inhibitors disclosed by Codd (p. 8, lines 3-8). In addition, it would have been obvious to the skilled artisan that Codd specifically contemplated celecoxib as a preferred COX-2 inhibitor to be used in combination with the tramadol of claim 1 since it is a claimed embodiment (claim 11).
Burch is cited to further show the obviousness of selecting celecoxib as the COX-2 inhibitor as well as provide further evidence that an artisan would expect synergy between celecoxib and an opioid analgesic such as tramadol.
Burch discloses synergistic combinations of an opioid analgesic and COX-2 inhibitor effective in treating pain (title; abstract; p. 6, lines 17-27; p. 12, lines 13-18). Burch emphasizes the synergistic effects of the disclosed combination throughout the document (e.g., title; p. 6, lines 26-27; p. 7, line 3 to p. 8, line 9; p. 9, lines 13-21; p. 10, lines 16-30; p. 21, line 29 to p. 22, line 4; claims 1-3, 16). Celecoxib is listed (and claimed) among a small group of preferred COX-2 inhibitors (p. 13, lines 25-28, claims 10, 15) and specifically taught to be a “super-selective” COX-2 inhibitor useful in the compositions of the invention (p. 14, lines 27-29; Table 1). Burch discusses celecoxib in detail on p. 14, lines 6-22 and teaches celecoxib as “a much more potent COX-2 inhibitor” that will provide significant synergy with opioid analgesics (p. 43, lines 9-11). Likewise, tramadol is listed (and claimed) among a small group of preferred opioid analgesics (p. 18, lines 1-13; p. 19, lines 10-18; claim 5). One would have been motivated to select celecoxib since Burch teaches it as a “super-selective” and potent COX-2 inhibitor useful in synergistic compositions with opioid analgesics such as tramadol.
Additionally, the obviousness inquiry must be performed as of the time the invention was made. See pre-AIA 35 U.S.C. 103(a). In this application, the effective date was October 2010. By that time, the person of ordinary skill in the art would have understood that celecoxib was the only selective COX-2 inhibitor disclosed by Codd in active use for treating pain. Specifically, rofecoxib (Vioxx®) was withdrawn from the market in 2004 due to its risk for adverse cardiovascular and thromboembolic events. See Chang, p. 178, 2nd col. Chang further teaches that celecoxib has beneficial effects on systolic blood pressure, actually ameliorated vascular injury, and has beneficial effects on inflammatory renal injury and endothelial dysfunction, all in contrast to rofecoxib (p. 179). Chang teaches that celecoxib has renoprotective benefits that are unique compared to rofecoxib and NSAID drugs (bridging pgs. 179-180). Thus, the person of ordinary skill in the art would further have recognized from Chang that celecoxib was the analgesic COX-2 inhibitor of choice in the field as of 2010. In addition to Burch's teachings, one would therefore have had further motivation to select celecoxib since Chang teaches celecoxib has beneficial effects on systolic blood pressure, ameliorated vascular injury, has beneficial effects on inflammatory renal injury and endothelial dysfunction, and has unique renoprotective benefits.
The person of ordinary skill in the art would also have known in 2010 that despite Codd's exemplification of JTE-522 (tilmacoxib) in 1999, that compound was never marketed to the public as an analgesic and was instead subsequently investigated for other therapeutic uses. For example, Yamamoto (published in 2003) describes tilmacoxib as a chemopreventive agent useful in treating experimental rat liver fibrosis (title; abstract). Importantly, in describing previous studies using JTE-522, Yamamoto teaches that it has been shown to inhibit tumorigenesis, but never states that it has been used as an analgesic (p. 557, 1st col). Indeed, Yamamoto never mentions pain or JTE-522 as having analgesic activity at all. Similarly, Kobayashi teaches JTE-522 as useful for treating colorectal cancer, but never states that it has been used as an analgesic (title; abstract, p. 920). The person of ordinary skill in the art reading Codd in 2010 and wishing to achieve Codd's goal of treating or preventing pain (see p. 6, lines 1-9; and claims 22-23 of Codd), therefore, would have focused on celecoxib, not JTE-522.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to select celecoxib as the COX-2 inhibitor in Codd’s compositions, and one would have a high expectation of synergy in doing so based on the disclosures of both Codd and Burch.
Instant claim 19 requires that the celecoxib is in neutral form. Claim 11 of Codd recites that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders claim 19 obvious by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form. Thus, Codd renders obvious the limitation of claim 19. Likewise, Burch teaches that both the opioid analgesic and the COX-2 inhibitor may be in the base (i.e., neutral) form or used as a pharmaceutically acceptable salt (p. 12, lines 19-22).
Instant claims 24 and 25 recite the limitation that the pharmaceutical composition is in tablet form and is a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22). Burch also teaches tablet forms for oral administration (p. 21, lines 24-28; claim 8).
Instant claim 26 recites a method of treating pain using the pharmaceutical composition of present claim 18. Codd teaches that one may use their pharmaceutical composition for treating pain (abstract; p. 6, lines 1-9; claims 16, 22 and 23). Burch also teaches a method of treating pain in humans (claims 18-23). Thus, the claim limitation is met.
Instant claims 30-32 recite the limitations that the pharmaceutical composition is in tablet form, is a single tablet, and is administered up to twice daily, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22) or in multiple doses depending upon the relative amount of each active component being used (p. 10, lines 6-22, especially, lines 11-15 and 19-22). On p. 10, lines 8-11, Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)).
Instant claims 33-35 recite various types of pain (acute, chronic, neuropathic nociceptive, mild, severe, moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, frozen shoulder, and sciatica) for which the racemic tramadol hydrochloride and celecoxib are administered. Codd teaches that the composition is used to treat conditions including osteoarthritis, rheumatoid arthritis, and cancer, as well as various types of pain, including acute, chronic, neuropathic, diabetic peripheral neuropathy, (par. bridging pgs. 10-11; claims 23-26). Burch also teaches a method of treating a variety of pain types, such as arthritis pain (including rheumatoid arthritis pain) (p. 22, lines 5-22; claim 24).
Claim 36 recites the limitation that the pain is severe to moderate pain. According to MPEP 804.II.B.1, the specification may be used as a dictionary to learn the meaning of a term in the claim. Col. 7, lines 7-8, discloses that severe to moderate pain is that of rheumatoid arthritis, ankylosing spondylitis, sciatica, and frozen shoulder. Thus, it would have been obvious to a skilled artisan at the time the invention was made that the limitation of claim 36 are met because Codd discloses that the pharmaceutical composition is used to treat rheumatoid arthritis (p. 11, line 5). Burch also teaches a method of treating a variety of pain types, such as arthritis pain (including rheumatoid arthritis pain) (p. 22, lines 5-22; claim 24).
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 obviousness-type 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); and 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
US Patent Application No. 17/968,253
Claims 18, 19, 24-26, and 30-69 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-7 of copending Application No. 17/968,253 in view of Codd (WO 0051685).
This is a provisional nonstatutory double patenting rejection.
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
Reference claim 5 of '253 recites a method of treating pain comprising administering to a patient a composition comprising racemic tramadol and celecoxib having a molecular ratio of 1:1. Reference claim 5 fails to disclose one or more pharmaceutically acceptable excipients. However, Codd which is in the same field of endeavor, renders obvious a composition comprising racemic tramadol hydrochloride and celecoxib having a molecular ratio of 1:1 to about 1:300 and from 1:1 to about 300:1 (preferably 1:1 to 1:30 and from about 1:1 to about 30:1) of tramadol material to a COX2 inhibitor (celecoxib) and one or more pharmaceutically acceptable carriers/excipients. Thus, it would have been obvious to a skilled artisan in view of reference claim 5 and Codd to incorporate a pharmaceutical excipient in a pharmaceutical composition for administration to a patient (p. 9, line 7 to p. 10, line 5). In addition, Codd discloses that tramadol material includes hydrochloride salt racemates (p. 6, lines 18-26) and exemplifies tramadol hydrochloride (p. 17, claim 4). Hence, claim 18 is obvious in view of reference claim 5 and Codd.
Instant claim 19 recites the limitation that the celecoxib is in neutral form. Claim 11 of Codd recites that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders claim 19 obvious by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form. Thus, Codd renders obvious the limitation of claim 19.
Claims 24 and 25 recite the limitation that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd discloses that tablets are a preferred dosage form a single tablet may be used.
Instant claim 26 which depends on claim 18 is directed to a method of treating of pain using the composition of claim 18.
Reference claims 5-7 disclose a method of treating pain (acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica) by administering the composition of (rac)-tramadol and celecoxib in a molecular ratio of 1:1. Codd, which is in the same field of endeavor as the present invention, renders obvious a composition comprising racemic tramadol hydrochloride and celecoxib in a 1:1 to about 1:300 and from 1:1 to about 300:1 (preferably 1:1 to 1:30 and from about 1:1 to about 30:1) ratio of tramadol material to a COX2 inhibitor (celecoxib) and one or more pharmaceutically acceptable carriers/excipients. Thus, it would have been obvious to a skilled artisan in view of reference claim 5 and Codd to incorporate a pharmaceutical excipient in a pharmaceutical composition for administration to a patient (p. 9, line 7 to p. 10, line 5). Hence, claim 26 is obvious in view of reference claims 5-7 and Codd.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches tablet form and that may be administered as a single tablet in one or multiple daily dosages (including twice daily) (p. 10, lines 6-22, especially, lines 11-15 and 19-22). Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd disclose that tablets are a preferred dosage form and one may administer the dose as a single tablet or the dosage may be given multiple times daily including twice.
Claim 33 recites that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Reference claim 7 which depends from claim 6 discloses that the pain is acute pain.
Instant claim 34 recites acute pain. Reference claim 7 which depends from claim 6 discloses that the pain is acute pain.
Instant claim 35 recites chronic pain. Reference claim 6 recites chronic pain.
Instant claim 36 recites severe to moderate pain. Reference claim 6 recites severe to moderate pain.
US Patent Application No. 17/609,452
Claims 18, 26, and 33-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14, 24, 25, and 29 of copending Application No. 17/609,452.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to methods of treatment of pain comprising administering a composition having racemic tramadol hydrochloride, celecoxib (in a ratio of 1:1), and one or more pharmaceutically acceptable excipients. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients. The composition of claim 18 is anticipated by reference claim 14.
Instant claim 26 recites a method of treatment of pain wherein the composition of claim 18 is administered. The method of claim 26 is anticipated by reference claim 14.
Instant claim 33 recites that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. '452 claims 24-25 which depend from claim 14 recite that the pain is acute pain, and '452 claim 29 recites fibromyalgia, rheumatoid arthritis, and frozen shoulder pain.
Instant claim 34 recites acute pain. Reference claims 24-25 which depend from claim 14 recite that the pain is acute pain.
Instant claim 35 recites chronic pain. Reference claims 24-25 recite chronic pain.
Instant claim 36 recites severe to moderate pain. Reference claims 24-25 recite severe to moderate pain.
Claims 19, 24, 25, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14, 24, 25, and 29 of copending Application No. 17/609,452 in view of Codd (WO 0051685).
This is a provisional nonstatutory double patenting rejection.
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein. In addition, the composition of claim 18 and method of claim 26 were anticipated under double patenting as set forth in the double patenting rejection above.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders obvious the use of celecoxib in neutral form by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form.
Instant claims 24 and 25 recite that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22) or in multiple doses depending upon the relative amount of each active component being used (p. 10, lines 6-22, especially, lines 11-15 and 19-22). On p. 10, lines 8-11, Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)).
US Patent 11,478,488
Claims 18, 19, 24-26, and 30-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of US Patent 11,478,488 in view of Codd (WO 00/51685).
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
'488 claims 3-4 which depend on claim 1 are directed to a method of treating pain by administering (rac)-tramadol hydrochloride and celecoxib in a 1:1 ratio for pain (including severe to moderate pain) ('488 claim 4). The '488 claims fail to recite that the administered of (rac)-tramadol hydrochloride and celecoxib is accompanied by one or more pharmaceutically acceptable excipients. Codd teaches that the pharmaceutical composition of claim 1 comprises a pharmaceutically acceptable excipient as the intended function of an excipient is to act as a carrier of the active components (bridging pgs. 9-10). It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate one or more excipients because Codd teaches it is well known in the art to administer a composition comprising tramadol and a COX-2 inhibitor using a pharmaceutical excipient.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders obvious the use of celecoxib in neutral form by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form.
Instant claims 24 and 25 recite that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26 recites a method of treatment of pain wherein the composition of claim 18 is administered. Reference claim 4 depends upon claim 1 and recites a method of treating pain wherein the pain is specifically severe to moderate or pain in general as in claim 1. Thus, reference claim 4 anticipates the limitation of claim 26.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22) or in multiple doses depending upon the relative amount of each active component being used (p. 10, lines 6-22, especially, lines 11-15 and 19-22). On p. 10, lines 8-11, Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)).
Instant claim 33 recites that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Reference claim 4 which depends from claim 1 recites that the pain is severe to moderate pain.
Instant claims 34 and claims 35, respectively recite acute and chronic pain. Reference claim 4, which depends on claim 1, recites that pain in general as well as severe to moderate pain is treatable with the combination of racemic tramadol hydrochloride and celecoxib. Codd discloses that this composition may be used to treat acute and chronic pain (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat acute and/or chronic pain in addition to severe to moderate pain. In light of Codd, the racemic tramadol hydrochloride/celecoxib combination would be obvious to use in treating acute and chronic pain addition to severe to moderate pain.
Claim 36 recites severe to moderate pain. Reference claim 4 recites the treatment of severe to moderate pain. Thus, reference claim 4 anticipates the limitation of claim 36.
US Patent 10,548,909
Claims 18, 19, 24-26, and 30-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US Patent 10,548,909 in view of Codd (WO 00/51685).
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
'909 claim 1 is directed to a method of treating severe to moderate pain by administering (rac)-tramadol hydrochloride and celecoxib in a 1:1 ratio. The '909 claims fail to recite that the administered of (rac)-tramadol hydrochloride and celecoxib is accompanied by one or more pharmaceutically acceptable excipients. It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate one or more excipients because Codd teaches that pharmaceutical compositions comprising tramadol and a COX-2 inhibitor (e.g., celecoxib) may comprise a pharmaceutically acceptable excipient, and the intended function of an excipient is to act as a carrier of the active components (bridging pgs. 9-10). Thus, it is well known in the art to administer a composition comprising a tramadol material and a COX-2 inhibitor (e.g., celecoxib) with a pharmaceutical excipient.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd recites that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders claim 19 obvious by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form. Thus, Codd renders obvious the limitation of claim 19.
Instant claims 24 and 25 recite the limitation that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26 which depends on claim 18 is directed to a method of treatment of pain using the composition of claim 18. Reference claim 1 recites a method of treating severe to moderate pain comprising administering (rac)-tramadol hydrochloride and celecoxib in a 1:1 ratio.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches tablet form and that may be administered as a single tablet in one or multiple daily dosages (including twice daily) (p. 10, lines 6-22, especially, lines 11-15 and 19-22). Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd discloses that tablets are a preferred dosage form and one may administer the dose as a single tablet or the dosage may be given multiple times daily including twice.
Instant claim 33 recites the limitation that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Reference claim 1 anticipates this limitation of claim 33 as it recites that the pain is severe to moderate.
Instant claims 34 and 35, respectively recite acute and chronic pain. Reference claim 1 recites a method of treating severe to moderate pain with racemic tramadol hydrochloride and celecoxib. Codd discloses that this composition may be used to treat acute and chronic pain (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat acute and/or chronic pain in addition to severe to moderate pain. In light of Codd, the racemic tramadol hydrochloride/celecoxib combination would be obvious to use in treating acute and chronic pain addition to severe to moderate pain.
Instant claim 36 recites severe to moderate pain. Reference claim 1 discloses the treatment of treat severe to moderate pain.
US Patent 10,238,668
Claims 18, 19, 24-26, and 30-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent 10,238,668 in view of Codd (WO 00/51685).
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
'668 claim 4 which depends on claim 1 is directed to a method of treating pain by administering (rac)-tramadol hydrochloride and celecoxib in a 1:1 ratio. Reference claim 4 fails to recite that the administered (rac)-tramadol hydrochloride and celecoxib is accompanied by one or more pharmaceutically acceptable excipients. Codd teaches that the pharmaceutical composition of claim 1 comprises a pharmaceutically acceptable excipient as the intended function of an excipient is to act as a carrier of the active components (bridging pgs. 9-10). It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate one or more excipients because Codd teaches it is well known in the art to administer a composition comprising tramadol and a COX-2 inhibitor using a pharmaceutical excipient.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders obvious the use of celecoxib in neutral form by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form.
Instant claims 24 and 25 recite that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26 which depends on claim 18 is directed to a method of treatment of pain using the composition of claim 18. Reference claim 4 recites a method of treating pain comprising administering (rac)-tramadol hydrochloride and celecoxib in a 1:1 ratio.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches tablet form and that may be administered as a single tablet in one or multiple daily dosages (including twice daily) (p. 10, lines 6-22, especially, lines 11-15 and 19-22). Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd disclose that tablets are a preferred dosage form and one may administer the dose as a single tablet or the dosage may be given multiple times daily including twice.
Instant claim 33 recites the limitation that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Codd teaches that the composition is used to treat acute, chronic, neuropathic, diabetic peripheral neuropathy, osteoarthritis, rheumatoid arthritis, and cancer (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art to treat various types of pain as in claim 33 because both Codd and the present invention are directed to tramadol and celecoxib containing compositions that treat overlapping types of pain.
Instant claims 34 and 35, respectively recite acute and chronic pain. Reference claim 4 recites that pain in general is treatable with a combination of racemic tramadol hydrochloride and celecoxib. Codd disclose that their composition may be used to treat acute and chronic pain (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat acute and/or chronic pain. In light of Codd, the racemic tramadol hydrochloride/celecoxib combination would be obvious to use in treating acute and chronic pain.
Instant claim 36 recites severe to moderate pain. Reference claim 4 recites the treatment of pain in general. According to MPEP 804.II.B.1, the specification may be used as a dictionary to learn the meaning of a term in the claim. When the specification is used to determine what is defined as severe to moderate pain, col. 7, lines 7-8, discloses that severe to moderate pain is that of rheumatoid arthritis, ankylosing spondylitis, sciatica, and frozen shoulder. Since Codd teaches that the pharmaceutical composition is useful to treat rheumatoid arthritis (p.6, lines 11-15; p. 11, line 5; claim 24), it would have been prima facie obvious to one of ordinary skill in the art to have used the composition to treat severe to moderate pain, such as that of rheumatoid arthritis.
US Patent 9,012,440
Claims 18, 19, 24-26, and 30-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent 9,012,440 in view of Codd (WO 00/51685).
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
'440 claim 1 is directed to a composition comprising (rac)-tramadol hydrochloride and celecoxib in a 1:1 molecular ratio. '440 claim 4, which depends from claim 1, recites a pharmaceutically acceptable medium, which reads on one or more pharmaceutically acceptable excipients.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders obvious the use of celecoxib in neutral form by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form.
Instant claims 24 and 25 recite that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26, which depends on claim 18, is directed to a method of treatment of pain using the composition of claim 18. The '440 claims fail to disclose that the composition may be used in the treatment of pain. Codd teaches a combination of a tramadol material and a selective COX-2 inhibitor having a synergistic effect useful for treating pain wherein the ratio of tramadol material and COX-2 inhibitor drug is from 1:1 to about 1:300 (entire document, especially, title; abstract; p. 5, lines 25 to p. 6, line 9; p. 16, lines 5-11). Thus, it would have been obvious to one of ordinary skill in the art to use the '440 composition for treating pain.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches tablet form and that may be administered as a single tablet in one or multiple daily dosages (including twice daily) (p. 10, lines 6-22, especially, lines 11-15 and 19-22). Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd disclose that tablets are a preferred dosage form and one may administer the dose as a single tablet or the dosage may be given multiple times daily including twice.
Instant claim 33 recites that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Codd teaches that the composition is used to treat acute, chronic, neuropathic, diabetic peripheral neuropathy, osteoarthritis, rheumatoid arthritis, and cancer (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art to treat various types of pain as in claim 33 because both Codd and the present invention are directed to tramadol and celecoxib containing compositions that treat overlapping types of pain.
Instant claims 34 and 35, respectively recite acute pain and chronic pain. Codd disclose that their composition may be used to treat acute and chronic pain (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat acute and/or chronic pain. In light of Codd, the racemic tramadol hydrochloride/celecoxib combination would be obvious to use in treating acute and chronic pain.
Instant claim 36 recites severe to moderate pain. According to MPEP 804.II.B.1, the specification may be used as a dictionary to learn the meaning of a term in the claim. When the specification is used to determine what is defined as severe to moderate pain, col. 7, lines 7-8, discloses that severe to moderate pain is that of rheumatoid arthritis, ankylosing spondylitis, sciatica, and frozen shoulder. Since Codd teaches that the pharmaceutical composition is useful to treat rheumatoid arthritis (p.6, lines 11-15; p. 11, line 5; claim 24), it would have been prima facie obvious to one of ordinary skill in the art to have used the composition to treat severe to moderate pain, such as that of rheumatoid arthritis.
US Patent 10,245,276
Claims 18, 19, 24-26, and 30-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of US Patent 10,245,276 in view of Codd (WO 00/51685).
The teachings of Codd as detailed in the 35 USC 103 rejection supra are incorporated herein.
Instant claim 18 is directed to a composition comprising a synergistic combination of (rac)-tramadol hydrochloride and celecoxib or a pharmaceutically acceptable salt or hydrate thereof having a molar ratio of about 1:1 in combination with one or more pharmaceutically acceptable excipients, where the tramadol and celecoxib are the only active pharmaceutical ingredients.
'276 claim 1 is directed to a composition comprising (rac)-tramadol hydrochloride and celecoxib in a 1:1 molecular ratio. Reference claim 3, which depends from claim 1, recites a pharmaceutically acceptable medium, which reads on one or more pharmaceutically acceptable excipients.
Instant claim 19 recites that the celecoxib is in neutral form. Claim 11 of Codd discloses that the COX-2 inhibitor is celecoxib and salts thereof. Codd's claim 11 renders obvious the use of celecoxib in neutral form by reciting the salt, which is a neutral form of celecoxib because a salt is a chemical compound consisting of an assembly of positively and negatively charged ions which results in a compound with no net electric charge (neutral form). In addition, the recitation of both "celecoxib" and, separately "salts thereof", teaches the neutral form to the ordinary artisan in this field since a skilled artisan would understand that a non-salt form of celecoxib would be the neutral (uncharged) form.
Instant claims 24 and 25 recite that the composition is in tablet form and a single tablet, respectively. Codd teaches that tablets are the most advantageous oral dosage unit form (p. 9, lines 20-23) and that the dosage unit may be administered in a single tablet (p. 10, lines 6-22, especially, lines 21-22).
Instant claim 26, which depends on claim 18, is directed to a method of treatment of pain using the composition of claim 18. The '276 claims fail to recite that the composition may be used in the treatment of pain. Codd teaches a combination of a tramadol material and a selective COX-2 inhibitor having a synergistic effect useful for treating pain wherein the ratio of tramadol material and COX-2 inhibitor drug is from 1:1 to about 1:300 (entire document, especially, title; abstract; p. 5, lines 25 to p. 6, line 9; p. 16, lines 5-11). Thus, it would have been obvious to one of ordinary skill in the art to use the '276 composition for treating pain.
Instant claims 30-32 recite that the composition is administered in tablet form, as a single tablet, and twice daily, respectively. Codd teaches tablet form and that may be administered as a single tablet in one or multiple daily dosages (including twice daily) (p. 10, lines 6-22, especially, lines 11-15 and 19-22). Codd discloses that a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients (preferably from 0.3 to 200 mg/day of the active ingredients) is administered. In addition, it would have been obvious to the skilled artisan that since Codd discloses that pharmaceutical compositions may be given at a daily dose of from about 0.1 mg/day to about 800 mg/day of the active ingredients in preferred dosages of 0.3 to 200 mg/day of the active ingredients, then multiple doses would be necessary (e.g., 0.3 to 200 mg/day (one dosage needed daily), 400 mg/day (two dosages needed daily), 600 mg/day (three dosages needed daily), and 800 mg/day (four dosages needed daily)). Thus, it would have been obvious to one of ordinary skill in the art to administer a single tablet because Codd disclose that tablets are a preferred dosage form and one may administer the dose as a single tablet or the dosage may be given multiple times daily including twice.
Instant claim 33 recites that the pain is acute, chronic, neuropathic, nociceptive, mild and severe to moderate, hyperalgesia, pain related to central sensitization, allodynia, cancer, diabetic neuropathy, diabetic peripheral neuropathy, osteoarthritis, fibromyalgia, rheumatoid arthritis, ankylosing spondylitis, and frozen shoulder or sciatica. Codd teaches that the composition is used to treat acute, chronic, neuropathic, diabetic peripheral neuropathy, osteoarthritis, rheumatoid arthritis, and cancer (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art to treat various types of pain as in claim 33 because both Codd and the present invention are directed to tramadol and celecoxib containing compositions that treat overlapping types of pain.
Instant claims 34 and 35, respectively recite acute and chronic pain. Codd disclose that their composition may be used to treat acute and chronic pain (bridging pgs. 10-11; p. 19, claim 23). Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to treat acute and/or chronic pain. In light of Codd, the racemic tramadol hydrochloride/celecoxib combination would be obvious to use in treating acute and chronic pain.
Instant claim 36 recites severe to moderate pain. According to MPEP 804.II.B.1, the specification may be used as a dictionary to learn the meaning of a term in the claim. When the specification is used to determine what is defined as severe to moderate pain, col. 7, lines 7-8, discloses that severe to moderate pain is that of rheumatoid arthritis, ankylosing spondylitis, sciatica, and frozen shoulder. Since Codd teaches that the pharmaceutical composition is useful to treat rheumatoid arthritis (p.6, lines 11-15; p. 11, line 5; claim 24), it would have been prima facie obvious to one of ordinary skill in the art to have used the composition to treat severe to moderate pain, such as that of rheumatoid arthritis.
Response to Arguments
Applicants' arguments have been fully considered but are not persuasive.
Applicants argue the fact that celecoxib was the preferred COX-2 inhibitor in the art is not supported by Codd, and represents unsupported examiner opinion (7/10/25 response, p. 7).
While this argument summarily dismisses the references previously supplied (Chang, Yamamoto, Kobayashi) to support the fact that celecoxib was the preferred COX-2 inhibitor in the art by 2010, said references have now been added to an additional rejection. Burch has also been added to further emphasize the expectation of synergy that an artisan would have had for the combination of tramadol and celecoxib.
The examiner has provided three different pieces of evidence (Chang, Yamamoto, Kobayashi) to support a conclusion that as of the time of the invention—which is the critical date, not the date of Codd’s publication—the person of ordinary skill in the art would have selected celecoxib as the COX-2 inhibitor over the others disclosed by Codd (see 3/11/25 final Office action, pg. 8.). Applicants have provided no evidence that as of 2010, the skilled artisan would have selected rofecoxib over celecoxib, even being aware of the teachings of Chang and the knowledge in the art that rofecoxib is undesirable for treating pain.
Applicants argue that the claims have been amended to be commensurate in scope with the limited data presented in the Merlos Declaration, asserting unexpected results (7/10/25 response, pgs. 7-11).
The Merlos declaration urges that one would not expect synergy from ANY of Codd's disclosed combinations because one combination (tramadol and tilmacoxib (i.e., JTE-522)) in one ratio did not achieve synergy (based on data later provided by applicants). However, it must be remembered that the Merlos declaration actually validates another embodiment of Codd's disclosure. Applicants are claiming a combination disclosed by Codd, which Codd teaches to be synergistic. Applicants are ultimately doing exactly what Codd disclosed and achieving the same result taught by Codd, which is what the person of ordinary skill in the art would have expected. Synergy between tramadol and celecoxib cannot be considered unexpected.
Independent from Codd, Burch also discloses synergistic combinations of opioid analgesics (including tramadol) and COX-2 inhibitors (including celecoxib). Burch emphasizes the synergistic effects of the disclosed combination throughout the document (e.g., title; p. 6, lines 26-27; p. 7, line 3 to p. 8, line 9; p. 9, lines 13-21; p. 10, lines 16-30; p. 21, line 29 to p. 22, line 4; claims 1-3, 16). Celecoxib is listed (and claimed) among a small group of preferred COX-2 inhibitors (p. 13, lines 25-28, claims 10, 15) and specifically taught to be a “super-selective” COX-2 inhibitor useful in the compositions of the invention (p. 14, lines 27-29; Table 1). Burch discusses celecoxib in detail on p. 14, lines 6-22 and teaches celecoxib as “a much more potent COX-2 inhibitor” that will provide significant synergy with opioid analgesics (p. 43, lines 9-11). Likewise, tramadol is listed (and claimed) among a small group of preferred opioid analgesics (p. 18, lines 1-13; p. 19, lines 10-18; claim 5). These teachings establish an additional expectation of synergy between the disclosed compounds (including tramadol and celecoxib), which is independent of Codd’s disclosure. The data presented in the Merlos declaration confirming the prior disclosures of both Codd and Burch cannot be considered unexpected.
While the Merlos declaration may show one embodiment of Codd (not claimed in the instant application) to be worse than expected, that is not the same as showing the claimed invention to be better than expected. Applicants have not sufficiently explained why their evidence of non-synergy for an unclaimed combination of agents negates Codd's teaching of synergy for the claimed combination. Expected beneficial results, such as synergy between tramadol and celecoxib (which synergy is disclosed by both Codd and Burch), are evidence of obviousness. See MPEP § 716.02(II). The record establishes a strong case of obviousness as of the time of the invention in light of the cited prior art teachings and the skilled artisan’s background knowledge and understanding of the field of selective COX-2 inhibitors as analgesics. Given the strength of the prima facie showing in this case, unexpected results may be ultimately insufficient to overcome the obviousness conclusion. See MPEP 2145.
Further, the teachings of Burch and Chang provide additional motivation to select celecoxib from Codd's disclosure since Burch teaches it as a “super-selective” and potent COX-2 inhibitor useful in synergistic compositions with opioid analgesics such as tramadol. Chang further teaches that celecoxib has beneficial effects on systolic blood pressure, actually ameliorated vascular injury, and has beneficial effects on inflammatory renal injury and endothelial dysfunction, all in contrast to rofecoxib (p. 179). Chang teaches that celecoxib has unique renoprotective benefits compared to rofecoxib and NSAID drugs (bridging pgs. 179-180). In addition to the fact that celecoxib was COX-2 inhibitor of choice as of 2010 and Burch's teachings, one would therefore have had further motivation to select celecoxib since Chang teaches celecoxib has beneficial effects on systolic blood pressure, ameliorated vascular injury, has beneficial effects on inflammatory renal injury and endothelial dysfunction, and has unique renoprotective benefits.
Applicants argue that Codd provides neither data nor guidance/direction for optimization (7/10/25 response, p. 8).
The Office never relied on a theory of “routine optimization” as incorrectly asserted by applicants on p. 8 of the response. Indeed, such a reliance was not necessary since Codd provides clear guidance and direction for the artisan to follow. Specifically, a 1:1 ratio is clearly disclosed as a dose tested in Example 1 of Codd, albeit using tramadol in combination with JTE-522 (see Codd, bridging pgs. 11-12). Nonetheless, an artisan reading Codd would find it obvious to use any of the other COX-2 inhibitors disclosed by Codd in the same ratios with tramadol tested by Codd, one of which is 1:1. Celecoxib would stand out as an especially obvious choice because by 2010, celecoxib was the only COX-2 inhibitor disclosed by Codd to be used clinically, and due to the advantages of celecoxib taught by Burch and Chang.
Regarding the double-patenting rejections, applicants argue that the conflicting claims require co-crystals of tramadol and celecoxib (7/10/25 response, p. 11).
However, the instantly claimed pharmaceutical composition is broader than the conflicting claims, and embraces any form(s) of tramadol and celecoxib, including co-crystals. The conflicting claims anticipate or render obvious the instantly claimed pharmaceutical composition, optionally in view of Codd as set forth in the rejections.
Conclusion
Claims 18, 19, 24-26, and 30-36 are rejected. No claims are allowable.
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/Kevin S Orwig/
Patent Reexamination Specialist, Art Unit 3991
Conferees:
/LBD/Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991
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