Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The office acknowledges Applicants filing of the claims on 7/19/2024. Claims 1-16 are pending and are examined based on the merits herein.
Application Priority
This application filed 07/19/2024 Claims Priority from Provisional Application 63528126, filed 07/21/2023.
Claim Rejections - 35 USC § 102
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 –
(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.
Claim(s) 1, 6-7 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Baxter (https://www.zoetisus.com/content/_assets/docs/vmips/package-inserts/robaxin-v_injectable.pdf, 2003).
Baxter teach ROBAXIN-V (methocarbamol) is a potent skeletal muscle relaxant which has an unusually selective action on the central nervous system, specifically on the internuncial neurons of the spinal cord that is formulated as injection or tablets (See p 1, lines 3-16).
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Further taught is that ROBAXIN-V injectable is supplied in 100 ml; each mL contains 100 mg of drug in sterile 50 percent aqueous solution of polyethylene glycol-300 vials (See p 2, Administration and Dosage).
Baxter’s teachings anticipate claims 1, 6-7 by teaching methocarbamol, a compound of formula I of claim 1, its composition as an injection or tablets and unit dosage injectable form. As to the limitation of ‘treating at least one muscle spasm related disease…and related diseases and conditions’, in claims 6-7, it is noted such limitations are to the intended use. Applicants are reminded that claim language which merely recites a purpose or intended use of a claimed invention that is otherwise fully and intrinsically set forth by the remainder of the claim, such language is of no consequence to the construction of the invention claimed. MPEP 2111.02(II). Statements of intended use do not serve to distinguish structure over the prior art. See In re Pearson, 494 F .2d 1399, 1403, 181 USPQ 641, 644 (CCPA 1974); In re Yanush, 477, F .2d 958, 959, 177 USPQ 705, 706 (In the instant case, the cited prior art meets each and every structural and physical limitation of the instantly claimed composition and, thus, would be reasonably expected to be capable of performing the intended uses as instantly claimed, absent factual evidence to the contrary and further absent any apparent structural difference between the composition of the cited prior art and that of the instant claims, CCPA 1973); In re Casey, 370 F .2d 576, 580, 152 USPQ 235, 238 (CCPA 1967).
Claim(s) 1, 6-7 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Koneru (US 11266621 B1),.
Koneru teach methocarbamol and a stable composition comprising methocarbamol (see abstract, claims). Koneru further teach methocarbamol is a muscle relaxant (col. 1, line 1). The structural formula of methocarbamol is:
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(See col. 1, lines 40-49).
Koneru teach injectable dosage formulations comprising methocarbamol (Tables 1-5, examples).
Koneru teachings anticipate claims 1, 6-7 by teaching methocarbamol, a compound of formula I of claim 1 and its injection composition unit dosage forms. As to the limitation of ‘treating at least one muscle spasm related disease…and related diseases and conditions’, in claims 6-7, it is noted such limitations are to the intended use. Applicants are reminded that claim language which merely recites a purpose or intended use of a claimed invention that is otherwise fully and intrinsically set forth by the remainder of the claim, such language is of no consequence to the construction of the invention claimed. MPEP 2111.02(II).
Claim 8 is rejected under 35 U.S.C. 102(A)(1) as being anticipated by Hess et al. (GB 2216520).
Hess et al. teachings relates to a process for the manufacture of the drug methocarbamol (3-(o-methoxyphenoxy)-1,2propanediol-l-carbamate). The reference teaches that process for the manufacture of methocarbamol by synthetic method (See Abstract, claims).
Hess teachings of the synthetic method of the manufacture of methocarbamol, a compound of formula I of claim 1 and thus anticipates claim 8.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 2, 4, 9-10 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Koneru (US 11266621 B1) and in view of the teachings in each of Dyck et al. (Journal of Neurochemistry Volume 46, Issue 2, pages 399-404 (1986)), Ando et al. (US 6,603,008), Foster (US 6,221,335), Gant et al. (US 2007/0082929), Potyen et al. (US 2007/0197695), and Wolen (Journal of Clinical Pharmacology, 1986, Volume 26, pages 419-424).
Koneru teachings as discussed above. The rejection above is incorporated herein.
Koneru is not explicit in teaching the deuterated compounds of claim 2 and 4.
Dyck et al. states, “Thus, deuterium substitution seems to be a useful strategy to enhance the pharmacological effects of a compound without significantly altering its basic chemical structure” (page 399, column 1).
Ando et al. teaches substitution with heavier isotopes such as deuterium, i.e. *H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances" (see column 6, lines 59-67 and column 7, lines 11-16).
Foster teaches that “by deuterating drugs, we have likely .. increased the lipophilic nature of the molecule” and, via the deuterium isotope effect, produced a derivative “less easily cleaved by metabolic (or destructive) processes. Hence, the elimination half-life of the drug is prolonged and the drug's therapeutic effects are increase” (column 17, lines 13- 32).
Gant et al., page 2, paragraph [0014] states, “Deuteration of pharmaceuticals to improve pharmacokinetics (PK), pharmacodynamics (PD), and toxicity profiles, has been demonstrated previously with some classes of drugs.
Potyen et al., page 2, paragraph [0013], “Deuteration can yield pharmaceuticals having improved bioavailability and reduced the toxicity.”
Wolen noting that the lack of toxicity for deuterium makes it “ideally suited for human studies” (abstract) concludes that “the application of stable isotope methodology to the problems of bioavailability and bioequivalence have proved extremely versatile and useful. The technique is simple and powerful and results in extremely low risk to the subject” (page 423). Thus, one is motivated to prepare deuterated drugs to gain these advantages.
The issue is whether substituting heavy hydrogen (or deuterium) for hydrogen is a patentable distinction to one of ordinary skill in the art. Various factors are taken into consideration when determining whether a change to a known compound is obvious. First, how well known is the compound? Second, what is the utility of the known compound in comparison to the changed compound? Third, how well known is the chemical process used to get from the known compound to the changed compound? Fourth, how well known is the process of deuterating organic compounds?
First, the derivative(s) of methocarbamol and the process of making it is known in the art. Second, methocarbamol is known to be useful as a muscle relaxant. Third, the chemical process used to get from the known methocarbamol to the deuterated methocarbamol is a common chemical process called an isotope exchange process. See Jerry March, Advanced Organic Chemistry, Fourth Edition, published 1992, pages 226-230. March teaches the isotope effects of deuterating compounds. It is acknowledged that deuterating compound changes the rate, but such changes are well known in the art and are known as deuterium isotope effects. This is an obvious change in a chemical compound and well known to a skilled artisan. Fourth, the process of deuterating organic compounds and commercially successful compounds in general is well known.
A person of ordinary skill in the art before the effective filing date of the invention would have found it obvious to arrive at the clamed deuterated derivatives of Koneru from the combined prior art teachings. A person skilled in the art would have been motivated to arrive at the claimed deuterated compounds with a reasonable expectation of success as alternative agents and use them as muscle relaxants. Moreover, given that there is always a need to enhance the pharmacological effects of a compound (e.g., increased in vivo half-life) without significantly altering its basic chemical structure (first branch), or that there is always a need to reduce the time, cost, risk, and statistical imprecision of pharmacokinetic studies (e.g., measure bioavailability or identify metabolites) (second branch), and that there is only a limited number of ways that this can be done, it would be obvious to pursue a potential solution that has a reasonable expectation of success. See e.g., KSR International Co.v. Teleflex Inc., 82 USPQ2d 1385, 1397 (U.S. Supreme Court 2007); Pfizer, Inc. v. Apotex, Inc., 82 USPQ2d 1321 (Fed. Cir. 2007); Alza Corp. v. Mylan Laboratories, Inc., 80 USPQ2d 1001 (Fed. Cir. 2006); In re Kubin, 90 USPQ2d 1417 (Fed. Cir. 2009); In re O’ Farrell, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988); In re Eli Lilly & Co., 14 USPQ2d 1741 (Fed. Cir. 1990); In re Ball Corp., 18 USPQ2d 1491 (Fed. Cir. 1991).
It would have been obvious to one of ordinary skill in the pharmaceutical art, before the effective filing date of the instant claimed invention, to have applied this known improvement technique in the same way to the compound of Koneru to obtain the results reasonably predictable from the secondary references. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1396 (U.S. Supreme Court 2007); Ruiz v. AB Chance Co., 69 USPQ2d 1686 (Fed. Cir. 2004); Nilssen, 7 USPQ2d 1500 (Fed. Cir. 1988). Thus claims 2, 4 would have been obvious over the prior art teachings. As to claims 9-10 and 13-14, a skilled artisan would have found it obvious to arrive at the claimed pharmaceutical composition and in the dosage unit forms from Koneru with a reasonable expectation of success because the reference is explicit in teaching a stable composition of methocarbamol and its unit dosage form.
Claim(s) 3, 5, 11-12 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Koneru (US 11266621 B1) in view of Patani et al. (Chem Rev, 1996, 96, 3147-3176) and Silverman (The Organic Chemistry of Drug Design and Drug Action, 1992, p 15-22).
Koneru teachings as discussed above. The rejection above is incorporated herein.
Koneru is not explicit in teaching the fluorine derivatives of claims 3 and 5.
Patani teachings focus on bioisosteres. Patani teaches that "A lead compound with a desired pharmacological activity may have associated with it undesirable side effects, characteristics that limit its bioavailability, or structural features which adversely influence its metabolism and excretion from the body. Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. The concept of bioisosterism is often considered to be qualitative and intuitive” (p 3147, col. 1 -2, Introduction). Patani further teach that “The ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties”. (See p 3148, col. 2, lines 8-10). Notably, as taught by Patani et al, one such generalization is that hydrogen can be replaced by Fluorine. Patani teach that the substitution of hydrogen by F is one of the more commonly employed monovalent isosteric replacements (see p 3149, col. 1).
Silverman teaches that bioisosteres are substituents or groups that have chemical or physical properties and which produce broadly similar biological properties (p 19, 4. Bioisosterism, lines 1-7).
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Accordingly, in view of Silverman and Patani et al it would have been prima facie obvious to a skilled artisan before the effective filing date of the instant claimed invention, that compounds with a fluorine substitution is a bioisostere and will exhibit similar biological/chemical/physical activity. One of ordinary skill in the art would have been motivated to substitute H for F and arrive at the compounds with a reasonable expectation of success and provide muscle relaxant benefits. Thus claims 3, 5 would have been obvious over the combined prior art teachings. As to claims 11-12 and 15-16, a skilled artisan would have found it obvious to arrive at the claimed pharmaceutical composition and in the dosage unit forms from Koneru with a reasonable expectation of success because the reference is explicit in teaching a stable composition of methocarbamol and its unit dosage form.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6-7, 10-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6-7, 9-16 recite a limitation of ‘related diseases or conditions’. it is not clear whether the diseases and conditions are related to ‘perioperative care of hip and knee replacements’ or is to all the muscle spasm related conditions that are listed in the claims. The specification do not teach what conditions and diseases are related to each condition to be treated as claimed. Thus, the metes and bounds of patent protection sought as instantly claimed for related diseases and conditions have not been defined. It is also noted that a disease is a specific, diagnosable pathological process with a known cause (e.g., a virus, genetic mutation, or organ malfunction). A condition is a broader, umbrella term that encompasses any state of health, illness, or abnormality—including diseases, injuries, or disabilities. While diseases are health conditions, not all conditions are diseases. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Appropriate correction is required.
Claims 7, 10, 12, 14 and 16 recite a limitation of ‘to a subject, animal or human,’. It is not clear whether the subjects are limited to animal or human. Further human is an animal. If the limitation is not limited to specific subject(s), then the claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Clarification is required.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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/Umamaheswari Ramachandran/ Primary Examiner, Art Unit 1627
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