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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/08/2026 has been entered.
Response to Arguments
Applicant’s arguments, see p. 6, filed 12/16/2025, with respect to the objection to claims 2 and 8 have been fully considered and are persuasive. Amendments moot the objection. The objection of 09/17/2025 has been withdrawn.
Applicant's arguments filed 12/16/2025 with respect to the obviousness rejection have been fully considered but they are not persuasive.
First, applicant argues that the present application solves the issues in the prior art with the use of sodium bicarbonate. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. First, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See MPEP 2144(IV). In the instant case, that the addition of sodium bicarbonate is alleged to solve a different problem does not negate that U.S. 8,546,453 B2 to Zhang teaches the use sodium bicarbonate to raise pH and therefore reduce injection pain (see Example, Col. 9-10). It is proposed that raising pH reduces free propofol and thereby reduces pain (Col. 4 line 53 - Col. 5 line 38). Sodium bicarbonate is taught as both an alkalizing agent and buffering agent (Col. 5, lines 46-48).
With respect to applicant’s second and third arguments on p. 9, applicant argues that Zhang et al. is directed toward propofol emulsions and therefore a PHOSITA would not apply the teachings to Mosher et al. Zhang et al. teaches that propofol has the disadvantage of causing pain upon injection (Col. 1 and 2) and “the administration of propofol at an alkalotic pH reduces or eliminates the pain normally associated with propofol administration” (Col. 4, lines 17-20). Sodium bicarbonate is used for said purpose as stated above. Importantly, there is no teaching nor suggestion that these teachings would not be applicable to the compositions taught by Mosher et al. regardless of the type of formulation. With respect to the arguments regarding choosing sodium bicarbonate, the Examiner respectfully disagrees. Mosher et al. clearly suggests administering at a pH of 6.5 or greater. Sodium bicarbonate is a recognized component to achieve said goal, and therefore would have been obvious to apply regardless of whether selected from a list.
Fourth, applicant argues that Zhang achieves its technical effect by adjusting pH and that the present invention differs. Applicant’s arguments are persuasive in part. Specifically, Examples 2 and 4 show the difference in free propofol when pH is constant but the amount of sodium bicarbonate is different. However, the claims are not commensurate in scope with these results in that they encompass a greater pH range and a greater range of amounts of sodium bicarbonate. Examples 11-16 each only teach that the pH is adjusted to 6-9; without constant pH, it is impossible to tell what variable is contributing to alleged unexpected results. It appears that there is some evidence of unexpected results, but the evidence is both inconclusive and not commensurate in scope with the claims.
Fifth, applicant argues that the prior art lacks the motivation of the inventors. As stated previously, The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. First, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See MPEP 2144(IV).
Applicant further argues that the buffer upper limit of sodium bicarbonate is approximately 8.31 and therefore would not have been obvious to select as a buffer. It is acknowledged that Formulation 2 of Mosher et al. is at a pH of 8.2. However, it is stated at p. 38, lines 27-28 that the solution contains 0.005% w/v disodium EDTA at pH 8.2 to mimic the DIPRIVAN formulation. There is no teaching of the criticality of EDTA or pH, only that they are used in the comparative formulation to mimic a version of DIPRIVAN with CBE7-B-CD.
Applicant argues a critical “window of operability”. These results are persuasive in part. There appears to be some degree of unexpected results as previously discussed with respect to Examples 2 and 4. However, the claims do not appear commensurate in scope with alleged unexpected results. The “window of operability” argued by applicant only appears for examples with 16g of cyclodextrin, for example, whereas the claims are drawn to 12-25% w/v SBE-beta-CD. It is not clear that these results can be extrapolated to the larger ranges of the instant claims.
Allegations of unexpected results appear to be the most promising path toward allowance, but the claims must be commensurate in scope with unexpected results. It is suggested that applicant both narrow the claims to those commensurate in scope with unexpected results and further explain how said results are commensurate in scope. Additional data may also be useful in determining whether unexpected results are significant and commensurate in scope.
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.
Claims 1, 3-4, 6-7, 13 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 03/080079 A1 to Mosher et al. and further in view of U.S. 8,546,453 B2 to Zhang.
Mosher et al teaches Formulations 1-3
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533
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which comprise 1% w/v propofol, 22% w/v sulfobutylether-beta-cyclodextrin and water for injection. Formulation 2 has a pH of 8.2. The pH is adjusted with sodium hydroxide/hydrochloric acid (see Example 1, p. 41-42). The cyclodextrin in the composition is equivalent to the sulfobutylether-beta-cyclodextrin as required by claim 8 (see pp. 3-4).
The claims differ from Formulation 2 of Mosher et al. in that they require the presence of 0.01-0.5% (w/v) sodium bicarbonate.
Mosher et al. teaches “the formulation of the present invention may include a conventional … buffering agent … alkalizing agent … “alkalizing agent” is intended to mean a compound used to provide alkaline medium for product stability … “buffering agent” is intended to mean a compound used to resist change in pH upon dilution or addition of acid or alkali.” Sodium bicarbonate is listed as an example of both an alkalizing agent and a buffering agent (see pp. 30-32). A PHOSITA would have found it obvious to include sodium bicarbonate in the composition in order to stabilize the product/resist change in pH as taught by Mosher et al. Note that the composition is specifically adjusted to 8.2 and it would have been obvious to incorporate a buffer such as sodium bicarbonate in order to stabilize the pH. Note also that such addition is described as “conventional” indicating it as a component of routine optimization in the art.
Furthermore, Zhang teaches “adding STP, sodium bicarbonate, or other alkalizing or buffering agents to propofol can significantly reduce the pain on injection” (Col. 9, lines 64-66). Amounts of 0.25% and 1.25% (w/v) are taught. 0.25% (w/v) lies within the instantly claimed range. While said amount does not improve pain (Tables 1 and 2), the disclosure suggests that merely raising the pH to 6.5 or greater (Col. 1, lines 17-36) is sufficient to reduce pain on injection. Accordingly, a PHOSITA would have optimized the amount of sodium bicarbonate to one within the instantly claimed range in order to adjust the pH as such with or without additional alkalizing and/or buffering agents (See MPEP 2144.05 II). Accordingly, it would have been prima facie obvious to include the claimed amounts of sodium bicarbonate in the mixture taught by Mosher et al. in order to decrease pain on injection as taught by Zhang. While the claimed amounts of free propofol (claims 6 and 15-16) are not disclosed by the prior art, they would have naturally flowed from the combined teachings of the prior art and cannot be considered nonobvious because Zhang proposes that raising pH reduces free propofol and thereby reduces pain (Col. 4 line 53 - Col. 5 line 38). It is understood that sodium bicarbonate reducing pain is a function of reduced free propofol. With respect to claim 17, Mosher et al. teaches sodium bisulfite as a conventional preservative and ascorbic acid (vitamin C) as an antioxidant (p. 31, lines 16-33), rendering their inclusion obvious.
Conclusion
Claims 1, 3-4, 6-7, 13 and 15-17 are rejected.
Claims 9-13 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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/JED A KUCHARCZK/ Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/ Primary Examiner, Art Unit 1621
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