DETAILED ACTION
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 .
Election/Restrictions
Applicant's election with traverse of endotoxemia in the reply filed on 5/4/2026 is acknowledged. The traversal is on the ground(s) that there would be no examination burden. This is not found persuasive because no rationale was provided to show why the Applicant believes that there is no examination burden. While the groups are generally linked by inflammation, both sepsis and COVID-19 can cause inflammatory conditions, but are not, themselves, characterized as inflammatory conditions; sepsis being a dysregulated immune response to infection, and COVID-19 being caused by the SARS-CoV-2 virus. If claims are found allowable, a rejoinder that specifically describes inflammation caused by sepsis and COVID-19 (within the independent claim), would be considered; however, given that sepsis and COVID-19 are not only inflammatory diseases, there would be scope of enablement issues if scope beyond inflammation was considered.
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-6, 10-13, 15, 23, 27-31, 33 and 53 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tracey, et al (US Pat. 12,109,255), Kim, et al (Journal of Chemical Neuroanatomy, 103, 101730, 2020), Vijayaraghavan, et al (PLoS One, 8, e65936, 2013 [IDS Reference]) and Rocha-Resende, et al (American Journal of Physiology: Cell Physiology, 320, C155-C161, 2021) and evidenced by Andreasen, et al (Current Medicinal Chemistry, 15, 1697-1705, 2008). Tracey teaches an identical choline acetyltransferase (ChAT). Tracey indicates that it can be PEGylated; Tracey notes that the composition is used to treat hypertension. See column 2, lines 9-15. There is no mention of endotoxemia.
Kim teaches methods of over-expressing ChAT, and notes that ChAT provides for anti-inflammatory properties. See page 1, “Abstract” section; page 6, “Discussion” section, 2nd paragraph; page 9, “Conclusion” section. Kim provides cells that overexpress ChAT, which would result in a method comprising administering ChAT, since Kim’s method would result in the administration of cells that overexpress ChAT, which, in essence, would be the same as provided exogenous ChAT. Although Kim teaches inflammation, Kim does not describe endotoxemia.
Both Vijayaraghavan and Rocha-Resende bolster the assertion that the ordinary artisan would understand that the adminstration of ChAT would provide for an increase in acetylcholine, which in turn, would result in anti-inflammatory properties. See Vijayaraghavan, page 1, “Abstract” section; page 2, left column, last paragraph [bridging to the right column]; Rocha-Resende, page c155, “Abstract” section; page c156, entire; page c157, right column. Based upon Kim, Vijayaraghavan, and Rocha-Resende, the ordinary artisan would understand that acetyl choline production, through the upregulation (or administration) of ChAT, would predictably lead to anti-inflammatory properties. The cited references only teach inflammation, they do not teach endotoxemia.
Andreasen provides a paper that indicates that endotoxemia can be used as a model for inflammation. See page 1697, “Abstract” and “Background” sections. This would suggest to the ordinary artisan that, since endotoxemia can be used as a model for inflammation, any method of treating inflammation would be obvious to try, wherein any method that is shown to provide clear anti-inflammatory properties would likely work in methods of treating endotoxemia. There would be a reasonable expectation of success because inflammatory pathways are well-known and understood, wherein there would be an expectation that is a treatment inhibited a particular inflammation pathway, it could be applied to any inflammation that elicits this type of inflammatory response. Andreasen also notes that acetylcholine signaling inhibits the inflammatory response, and acetylcholine esterase enhances proinflammatory responses. See page 1701, “Humoral Responses” section. This would further suggest to the ordinary artisan that control of acetylcholine, especially its upregulation, would predictably lead to an inhibition of inflammation.
With respect to claim 1, Tracey teaches the composition, while Kim, Vijayaraghavan, and Rocha-Resende provide rationale to suggest that Tracey’s composition could be used to treat inflammation. Andreasen shows that endotoxemia can be used as a model for inflammation, suggesting that the inflammation taught by Kim, Vijayaraghavan and Rocha-Resende could be treated with Tracey’s composition, wherein ChAT upregulates in vivo acetylcholine levels.
With respect to claims 2 and 3, the cited prior art teaches both humans and animals. However, it is well-known that animal models are used for human treatments, and as such, there would be a reasonable expectation that treatments for one animal with cholinergic signaling would apply to any other animal with the same type of cholinergic signaling.
With respect to claims 4 and 5, Tracey teaches ChAT, and PEGylated ChAT, both with pharmaceutically acceptable carriers. See column 2, lines 9-15.
With respect to claim 6, Tracey teaches the same PEGylation. See column 3, lines 29-35.
With respect to claim 10, as discussed above, inflammation overlaps with endotoxemia, and as such, there would be a reasonable expectation that a treatment for inflammation would apply to endotoxemia.
With respect to claims 11 and 12, Andreasen indicates that acetylcholine esterase activity increases the pro-inflammatory response. See page 1702, right column, top three lines. This would suggest to the ordinary artisan that if the goal is to prevent or reduce inflammation, acetylcholine esterase activity should be eliminated. This can predictably be performed with an inhibitor of acetyl choline. Since the ordinary artisan can routinely find acetylcholine esterase inhibitors, as these are commercially available, it would be obvious to use those that are well-known and widely-used. The claimed inhibitors are well-known and widely-used.
With respect to claim 13, as is clear from the cited prior art, the enzymatic pathway for the formation of acetyl choline, from ChAT is well-known and highly documented. Based on the prior art, it would be clear to the ordinary artisan that choline is a substrate that can be converted into acetylcholine, by using ChAT. It would be obvious to the ordinary artisan to further include exogenous choline, as this would prevent the substrate choline to not be the rate limiting reactant in the enzymatic reaction performed by ChAT.
With respect to claims 15 and 23, based on the cited prior art, there would be a reasonable expectation that the ChAT treatment of Tracey would work on any types of inflammation that are caused through cholinergic signaling, because Andreasen indicates that cholinergic signaling can be pro-inflammatory, and its inhibition would be expected to be anti-inflammatory.
With respect to claims 27-31 and 53, in the instant scenario the ordinary artisan would be a physician that specializes in rheumatology, immunology, gastroenterology, endocrinology, or any other specialization that works with inflammation. Since the ordinary artisan understands that disease-related inflammation should be reduced, there would be a reasonable expectation that these physicians would use well-known and widely-used anti-inflammatory compounds to further augment the ChAT therapy; the use of multiple known therapies is routine in the art, especially when it utilizes compounds that are well-known and widely-used to treat inflammation. It would be obvious to add other known anti-inflammatories, because it is clear that ChAT functions on the cholinergic pathway, whereas other anti-inflammatories act upon other pathways. There would be an expectation that providing anti-inflammatory compounds to multiple inflammatory pathways would lead to greater treatment than only providing treatment to one pathway. The specifically cited steroidal and non-steroidal anti-inflammatories include many over-the-counter medications, as well as well-known and widely-used prescription anti-inflammatories. These would be obvious to use.
With respect to claim 33, based on the prior art, there would be a reasonable expectation that the administration of ChAT would lead to the claimed physiological response.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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