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 .
Status of Claims
Claims 1-7 and 16-17 are pending in the instant application. Claims 1 and 17 are amended and claims 8-15 and 18-19 are cancelled via the amendment filed July 1st, 2026.
Priority
This application claims priority to foreign application CN202310557089.0, filed May 16th, 2023. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 1st, 2026 has been entered.
Withdrawn Rejections
Applicant’s arguments, filed July 1st, 2026, with respect to the 35 U.S.C. 102 rejection of claims 1-9 and 15-16 as being unpatentable over Repine have been fully considered and are persuasive. The 35 U.S.C. 102 rejection of claims 1-19 and 15-16 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to recite “ wherein the ergothioneine and/or pharmaceutically acceptable salt thereof is loaded in a nano-sized pharmaceutical carrier having a particle size of 200 nm or less, wherein the nano-sized pharmaceutical carrier is nanovesicles prepared by artificial extrusion from Human umbilical cord mesenchymal stem cell”
Applicant’s arguments, filed July 1st, 2026, with respect to the 35 U.S.C. 103 rejections of claims 1-11, 13 and 16-17 as being unpatentable over Repine, Lim and Jong have been fully considered and are persuasive. The 35 U.S.C. 103 rejection of claims 1-11, 13 and 16-17 has been withdrawn.
Applicant has overcome this rejection by amending claim 1 to recite “ wherein the ergothioneine and/or pharmaceutically acceptable salt thereof is loaded in a nano-sized pharmaceutical carrier having a particle size of 200 nm or less, wherein the nano-sized pharmaceutical carrier is nanovesicles prepared by artificial extrusion from Human umbilical cord mesenchymal stem cell”
Also, amending claim 17 to recite that the ergothioneine is loaded in a “carrier having a particle size of 200 nm or less” prepared by artificial extrusion “from Human umbilical cord mesenchymal stem cells”.
Response to Remarks
Applicant’s arguments regarding the 102 and 103 rejections are moot as the rejections have been overcome by Applicant’s amendments.
Applicant’s arguments regarding the Repine reference will be addressed below, as the new 35 U.S.C. 103, as necessitated by Applicant’s amendment, only relies on this references from the previous rejection.
On p. 7 of the remarks, Applicant argues that Repine relies on a model of localized lung injury and a POSITA would not have expected that a treatment for localized lung damage would effectively reverse the complex, systemic multi-organ failure that characterizes sepsis, from reading Repine.
However, instant claim 1, in part, is drawn to a method of treatment of sepsis or a sepsis related disease in a subject in need thereof comprising administering ergothioneine. As such, the claim only requires that ergothioneine is administered to patients with sepsis. Further, as stated in the previous Office action, Repine teaches a method of treating a subject with alveolar capillary membrane injury, the method comprising administering to the subject a therapeutically effective amount of ergothioneine and a pharmaceutically acceptable carrier, wherein the alveolar capillary membrane injury is a symptom of sepsis (claim 2). As such, Repine teaches the administration of ergothioneine to a patient with sepsis, as required, in part, by instant claim 1.
Additionally, in the response, Applicant has filed a declaration under 37 C.F.R. 1.132 accompanied by Exhibit A. The declaration and Exhibit A has been considered by the Examiner. However, the declaration under 37 CFR 1.132 filed July 1st, 2026, while sufficient to overcome the rejections in the previous Office action, is insufficient to overcome the new rejections as necessitated by Applicant’s amendments for the reasons below.
On p. 2 of the declaration, it is stated that Exhibit A was obtained using dosages within the claimed range of 1-50 mg/kg. However, Fig.1 and Fig. 5 of Exhibit A uses 5 mg/kg and 1.63 mg/kg of EGT. Further, the examples presented in the declaration are merely concerned with mouse models. It is unclear how results in an animal model would correlate with treatment in a human patient. Further, instant claim 1 is drawn to not only the treatment of sepsis but also, the treatment of a sepsis related disease.
Whether the unexpected results are the result of unexpectedly improved results or a property
not taught by the prior art, the “objective evidence of no obviousness must be commensurate in scope
with the claims which the evidence is offered to support.” In other words, the showing of unexpected
results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622
F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02 (d) and MPEP 716.02 (e).
Further, a new piece of art has been used in the rejection necessitated by Applicant’s amendment that teaches that specific use of human umbilical cord mesenchymal cells for the treatment of sepsis, see below. The newly presented piece of art teaches the use of human umbilical cord mesenchymal cells nanovesicles for the treatment of sepsis. The new art also teaches that these nanovesicles are anti-inflammatory and aid in accumulation of the drug, which are the alleged surprising results. Thus, Applicant has not yet compared the claimed subject matter with the closest prior art, as Applicant’s amendment has necessitated a new 35 U.S.C. 103 rejection. An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closes prior art to be effective to rebut a prima facie case of obviousness. In re Buckle, 592 F.2d
1175, 201 USPQ 67 (CCPA 1979).
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 1-7 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Repine et al (US 2011/0160268 A1, published June 30th, 2011) in view of Jing et al (Front. Cell. Infect. Microbiol., 06 April 2022).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Repine teaches a method of treating a subject with alveolar capillary membrane injury, the method comprising administering to the subject a therapeutically effective amount of ergothioneine and a pharmaceutically acceptable carrier, wherein the alveolar capillary membrane injury is a symptom of sepsis (claim 2). Repine also teaches a 15 mg/kg dose of ERGO (Example 4).
Repine further teaches that the selection of the pharmaceutically acceptable carrier, adjuvant or vehicle will depend on a variety of factors that include, but are not limited to, the route of administration, dosage levels, the age, weight or condition of the subject, etc. (paragraph [0035]). Also, compositions may be prepared by any method known in the art of pharmacy, for example by admixing the active ingredient with the carrier(s) or excipient(s) under sterile conditions. Such compositions also include liposomal com positions as drug carriers (paragraph [0036]).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Repine does not explicitly teach that the ergothioneine is loaded in a nano-sized pharmaceutical carrier prepared from Human umbilical cord mesenchymal stem cells.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Jing teaches that extracellular vesicles (EVs) are serving as new messengers to mediate cell-cell communication in vivo and the potential application for EVs in diagnosis, prevention and treatment for sepsis (abstract). Specifically, Jing teaches the use of human umbilical cord mesenchymal stem cells and the benefits of the use of these cells. Jing teaches that human umbilical cord mesenchymal stem cells (huc-MSCs) inhibit the expression of inflammatory cytokine by transferring miR-377-3p. Also, that the cells have been proven to have therapeutic benefits, including reducing acute inflammation, promoting alveolar epithelial regeneration and lung endothelial cell repair (page 9, right column). Jing further teaches that the EVs range in sizes from 40-200nm (page 2, left column, paragraph 2).
Jing teaches that currently, there is a mainstream insight regarding the latest treatment strategies of EVs in sepsis, immune cells derived EVs as drug delivery carriers to treat sepsis (page 9, right column, paragraph 2). Further, Jing teaches that as drug delivery carriers, EVs also have great research prospects in the treatment of sepsis (page 10, right column, paragraph 2) .
Thus, regarding claim 1, as Repine teaches the use of ergothioneine for the treatment of sepsis, one of ordinary skill in the art looking to optimize the general pharmaceutical carrier teachings of Repine, would’ve looked to Jing to arrive at the instant invention as Jing teaches that human umbilical cord mesenchymal stem cells, having a size less than 200 nm, are great drug delivery carriers in the treatment of sepsis. Regarding claim 17, as a method of treating sepsis with ergo theine loaded in a human umbilical cord mesenchymal stem cell is rendered obvious, as is the product itself.
Regarding claims 3-5, the prior art is silent regarding "amelioration of a disease symptom or improvements in health in the subject, alleviates lung inflammation, alleviates pulmonary edema, protein leakage and vascular injury, and improves lung oxygenation and inhibits phosphorylation activation of the TLR-4/MyD88/NF-kB ". However: "amelioration of a disease symptom or improvements in health in the subject, alleviates lung inflammation, alleviates pulmonary edema, protein leakage and vascular injury, and improves lung oxygenation and inhibits phosphorylation activation of the TLR-4/MyD88/NF-kB " will inevitably flow from the method made obvious by the teachings of the prior art (see above rejection), since the same compound (ergothioneine)) is being administered to the same subjects (a subject suffering from sepsis). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
In other words, even though the prior art is silent regarding "amelioration of a disease symptom or improvements in health in the subject, alleviates lung inflammation, alleviates pulmonary edema, protein leakage and vascular injury, and improves lung oxygenation and inhibits phosphorylation activation of the TLR-4/MyD88/NF-kB " by practicing the method made obvious by the prior art: "the administration of ergothioneine to a patient suffering from sepsis", one will also be "amelioration of a disease symptom or improvements in health in the subject, alleviates lung inflammation, alleviates pulmonary edema, protein leakage and vascular injury, and improves lung oxygenation and inhibits phosphorylation activation of the TLR-4/MyD88/NF-kB " even though the prior art was not aware of it.
Apparently, Applicant has discovered a new property or advantage ("amelioration of a disease symptom or improvements in health in the subject, alleviates lung inflammation, alleviates pulmonary edema, protein leakage and vascular injury, and improves lung oxygenation and inhibits phosphorylation activation of the TLR-4/MyD88/NF-kB " of the method taught by the prior art ("the administration of ergothioneine to a patient suffering from sepsis").
MPEP 2112 I states: “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
Regarding claim 6, Repine teaches that N-acetyl cysteine (NAC) or alpha-lipoic acid is co-administered with ergothioneine (claim 3). Repine further teaches that NAC is administered at the same time as the ergothioneine (claim 4).
Regarding claim 7, Repine teaches that the route of administration of intraperitoneal, intramuscular or intravenous (paragraph [0024]).
Regarding claim 16, Repine teaches that “subject” more particularly means a human primate (paragraph [0021]).
Conclusion
No claim is allowed.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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