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 .
Claims 1-5 and 16-23 are presented for examination.
Restriction/election
Applicant’s election without traverse of Group I, claim 1-5 in the reply filed on 12/17/2025 is acknowledged.
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) 1-5 and 16-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitidieri et al. (US 20170049720 submitted by the applicant) in view of Dinnequin (20050070613 submitted by the applicant) and further in view of Rakesh et al. (US 20160058715 submitted by the applicant).
The claims are drawn to a process for producing a stable, injectable solution containing noradrenaline, comprising the following steps:
a)dissolving noradrenaline and optionally one or more excipients in deoxygenated or
degassed water, in order to produce a solution containing noradrenaline;
b)distributing the noradrenaline solution in an inert gas current into a container,
c)sterilizing the solution containing noradrenaline, before and/or after step b),
d)hermetically sealing the container,
e)wherein the oxygen concentration in the solution containing noradrenaline is less
than 300 ppbw immediately after sealing the container; and
f)wherein the oxygen concentration in the headspace immediately after sealing the
container is at most 1.0 percent v/v.
regarding claim 1, Mitidieri et al. teach a process for producing a stable, injectable solution with low content of noradrenaline, which includes dissolving noradrenaline and optionally an excipient in deoxygenated or degassed water, filtrating the resulting noradrenaline solution in a nitrogen current, distributing the solution in a nitrogen current, and sterilization, preferably hot. Mitidieri et al. teach the process further provides a stable, injectable solution with low content of noradrenaline, substantially free of anti-oxidizing and preservative agents, as well as uses thereof in the medical and pharmaceutical fields. See the abstract and Para [0020]. Mitidieri et al. teach processes were adopted for the production of noradrenaline injectable solutions, which took advantage of high vacuum packaging technologies. See Para [0013]. Mitidieri et al. teach a process for the production of a noradrenaline injectable solution, in particular with a content of noradrenaline of 0.04 to 0.20 mg/ml. See Para [0038]. The concentration of oxygen in the solution of adrenaline is taught to be lower than 100 ppb. See Para [0049]. Mitidieri does not teach the concentration of oxygen in the head space and hermetically seating the container.
Dinnequin et al. teaches a method for producing sterile stable solutions of phenolic substances and resulting stabilized antioxidant- free solutions of phenolic substances (e.g. noradrenaline) with pH at 3.0 -5.0 containing not more than 0.02 ppm (i. e. 20 ppb) of oxygen in the solution. See (abstract, [0005], [0016], Examples 1-9 and claims 1-12. Dinnequin teaches dissolved oxygen content in noradrenaline injection solution at 0.01-0.02 ppm (i. e. 10 ppb- 20 ppb, [0104]) in the process and at 0.83 or 0.98 ppm (i. e. 830 ppb or 980 ppb) in the finished product ([0105], [0106]). Dinnequin also teaches oxygen content in the headspace is 1.6-3.0% V/V. See Paras ([0107],[0108]).
Rakesh et al. teach a ready-to-administer parenteral dosage form comprising an aqueous solution comprising a therapeutically effective amount of norepinephrine or its pharmaceutically acceptable salt. See Claim 1. Rakesh et al. teach the dosage form is used in an infusion bag and wherein norepinephrine is present in the aqueous solution in an amount ranging from about 0.004 mg/ml to about 0.15 mg/ml. See claim 13.
It would have been obvious to a person skilled in the art to use the concentration 1.0 percent oxygen in headspace, considering that Dinnequin teaches the presence of oxygen in the headspace in the container of noradrenaline. The determination of optimum amounts of oxygen in the head space of noradrenaline is considered to be within the skill of artisan in the absence of evidence to the contrary. Applicant’s attention is drawn to In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the court stated “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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."
It would have also been obvious to a person skilled in the art to use a sealed container for storing epinephrine, motivated by the teachings of Rakesh, which teaches injectable epinephrine has been stored in an infusion bag, which is inherently sealed.
Regarding claim 2, Mitidieri does not the oxygen content of less than 600 ppbw. However, Dinnequin et al. teach a method for producing sterile stable solutions of phenolic substances and resulting stabilized antioxidant- free solutions of phenolic substances (e.g. noradrenaline) with pH at 3.0 -5.0 containing not more than 0.02 ppm (i. e. 20 ppb) of oxygen in the solution. See (abstract, [0005], [0016], Examples 1-9, claims 1-12). It would have been obvious to a person skilled in the art to use noradrenaline with the oxygen content of less than 600ppbw, motivated by the teaching of Dinnequin, which teaches the oxygen content of not more than 0.02 ppm (i. e. 20 ppb) in a noradrenaline solution.
Regarding claim 3, Mitidieri does not teach the wherein the oxygen concentration in the headspace container is 0.15 to 1.0 percent v/v. Dinnequin teaches the oxygen concentration in the headspace of 1.6-3.0 percent v/v, which is higher than the claimed concentration. However, the determination of optimum amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 4, Neither Mitidieri or Dinnequin teach the volume of headspace. However, the determination of headspace volume is considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 5, Mitidieri teaches the concentration of 0.04 to 0.20 mg/ml of noradrenaline, which encompasses the claimed concentration of 0.1 mg/ml.
Regarding claim 16, Mitidieri teaches the concentration of oxygen in the solution of noradrenaline is taught to be lower than 100 ppb, which reads on the concentration of less than 340 ppbw.
Regarding claim 17, Mitidieri does not teach the wherein the oxygen concentration in the headspace container is 0.2 to 1.0 percent v/v. Dinnequin teaches the oxygen concentration in the headspace of 1.6-3.0 percent v/v, which is higher than the claimed concentration. However, the determination of optimum amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 18, , Mitidieri does not teach the wherein the oxygen concentration in the headspace container is 0.3-0.95 percent v/v. Dinnequin teaches the oxygen concentration in the headspace of 1.6-3.0 percent v/v, which is higher than the claimed concentration. However, the determination of optimum amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 19, Neither Mitidieri or Dinnequin teach the volume of headspace. However, the determination of headspace volume is considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 20, Neither Mitidieri or Dinnequin teach the volume of headspace. However, the determination of headspace volume is considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 21, Mitidieri teaches the concentration of 0.04 to 0.20 mg/ml, which concentration of 0.04 mg/ ml is less than the claimed concentration of 0.06%.
Regarding claim 22, Mitidieri teaches the concentration of 0.04 to 0.20 mg/ml of noradrenaline, which 0.04 mg/ml is very close to less than 0.04 mg/ml. Furthermore, the determination of optimum proportions or amounts are considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 23, Mitidieri teaches the concentration of 0.04 to 0.20 mg/ml, which overlaps with the claimed concentration of 0.04.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617