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
This Office Action is in response to Applicant’s Arguments and Amendment filed, 05/21/2026, wherein the Amendment amended claims 1, 9, 12, and cancelled claims 2-6.
Claims 1, 7, 9, and 12 are pending.
Priority
This application claims the following priority:
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REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Claim Objections
Applicant’s deletion of claim 3 is sufficient to overcome this objection.
35 U.S.C. § 112(a)-Scope of Enablement
Applicant’s amendments to independent claims 1 and 12 are sufficient to overcome this rejection.
35 U.S.C. § 103
Applicant’s amendment to independent claims 1, 9, and 12, which deletes “or an agonist of PGE2 receptor,” is sufficient to overcome these rejections since the primary reference, Nitta, teaches ONO-AE1-329, an agonist of PGE2 receptor.
REJECTIONS-NEW
Applicant’s amendments to the claims have resulted in the new rejections.
Claim Rejections - 35 USC § 112(a)-New Matter Rejection
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection.
The recitations “A method of treating colitis” in claim 1, line 1, and “colitis is ulcerative colitis or Crohn’s disease” in claim 7 are new matter.
Applicant points to [0008], [0020], [0026] and [0048]-[0058], Examples 1-3 for support, however none of these paragraphs or examples provides support for treating colitis. It appears that Applicant is referencing US PG Pub. 2024/0082263 (PTO-892) since the instant specification does not contain paragraph numbers. None of [0008], [0020], or [0048]-[0058] recite colitis, let alone the colitis being ulcerative colitis or Crohn’s disease. While [0026] teaches the treatment of “ulcerative colitis” and “ischemic colitis,” neither “ulcerative colitis” nor “ischemic colitis” provide support for treating “colitis” in general, or provide support for colitis being ulcerative colitis or Crohn’s disease, as recited in instant claims 1 and 7, respectively.
Moreover, a careful review of the original disclosure and claims does not provide support for these recitations.
Claim Rejections - 35 USC § 112(b)
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.
Claim 7 is 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.
Regarding the phrase “colitis is ulcerative colitis or Crohn’s disease” in claim 7, it is not clear how Crohn’s disease is colitis since Crohn’s disease is not a type of colitis.
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 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, 9, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over in Cuzzocrea (Melatonin reduces dinitrobenzene sulfonic acid-induced colitis, published 2001, PTO-892) view of Peng (COX-1/PGE2/EP4 alleviates mucosal injury by upregulating beta-arr1-mediated Akt signaling in colitis, published 2017, PTO-892).
Cuzzocrea teaches melatonin as reducing colitis (title). Melatonin reduces diarrhea, reduces body weight loss, ameliorates the disruption of colonic architecture, reduces colonic myeloperoxidase activity, reduces malondialdehyde levels, reduces the appearance of nitrotyrosine and poly(ADP-ribose) synthetase immunoreactivity in the colon, reduces the upregulations of ICAM-1, reduces the expression of P-selectin, and more, in colitis (abstract; pg. 10, Col. 2).
Regarding claims 1, 9, and 12, while Cuzzocrea teaches a method of treating colitis by administering melatonin, it differs from that of instant claim 1 in that it does not teach a composition further comprising PGE2.
Peng teaches that PGE2 treatment alleviates mucosal injury and induces EP4 expression in colitis (abstract), and that PGE2 has favorable therapeutic effects on ulcerative colitis (pg. 9, 1st full paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to combine the methods of Cuzzocrea and Peng, to arrive at a method of treating colitis by administering a composition comprising melatonin and PGE2. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
-both Cuzzocrea and Peng are directed toward methods of treating colitis, and
-"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06
As such, an ordinary skilled artisan would have been motivated to make such a modification to predictably arrive at a more potent and therapeutically effective method of treating colitis that reduces diarrhea, reduces, the loss of body weight, and alleviates mucosal injury.
Further regarding claims 1, 9, and 12, while the combination of Cuzzocrea and Peng does not teach the µM amounts of melatonin or PGE2, the optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
Moreover, Cuzzocrea teaches administration of 15mg/kg of melatonin daily and the instant specification teaches that the instant composition can be administered in a range of 0.1 to 10,000 mg/kg ([0033]), and Peng teaches administration of 200µg/150µ/20g body weight of PGE2 to mice. As such, it is known in the art to optimize amounts of melatonin and PGE2 to treat colitis.
Thus, an ordinary skilled artisan would have been motivated to make such µM selections of melatonin and PGE2, to predictably arrive at the most therapeutically effective concentrations of melatonin and PGE2 to treat colitis.
Regarding the wherein clauses in the last three lines of claim 1 and the last two lines of claim 12, MPEP 2111.04 states that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, “wherein the administering induces revival stem cells in intestinal epithelial cells of the subject, the revival stem cells being characterized by increased expression of one or more markers selected from the group consisting of clusterin, Ly6a, and Claudin-4,” in claim 1, and “wherein the contacting increases expression of one or more markers selected from the group consisting of clusterin, Ly6a, and Claudin-4 in the intestinal epithelial organic,” in claim 12, express the desired result of the positive step of administering a composition comprising therapeutically effective amounts of melatonin and PGE2 to a patient with colitis. As such, these limitations are met by the combined method of Cuzzocrea and Peng. See also MPEP 2112.02.
Further regarding claim 12, while the combination of Cuzzocrea and Peng does not explicitly recite “inducing revival stem cells in intestinal epithelial organoids,” it recites the same method step of administering a composition comprising melatonin and PGE2, to a patient population in need of “inducing revival stem cells,” i.e., patients with colitis, in amounts effective to treat colitis. As such, the combined method of Cuzzocrea and Peng would necessarily induce revival stem cells in intestinal epithelial organoids following administration of the composition. See MPEP 2112.02, the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607.
Moreover, the instant specification teaches that when intestinal epithelial organoids are treated with melatonin and PGE2, the expression of revival stem cell makers increases. The instant specification teaches this composition for use in preventing, treating, or improving intestinal epithelial injury diseases ([0015], PG Pub) and teaches colitis as an intestinal epithelial injury diseases ([0026], PG Pub).
Further regarding claim 9, it is noted that the phrases “for inducing revival stem cells in intestinal organoids” and “wherein the composition, when contacted with the intestinal epithelial organoids increases expression of one or more markers selected from the group consisting of clusterin, Ly6a, and Claudin-4 in the intestinal epithelial organoid,” are intended use recitations. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. Since the combination of Cuzzocrea and Peng teaches the instantly claimed composition, the composition of Cuzzocrea and Peng is capable of performing the intended use, and therefore meets the intended use limitation of claim 9.
Regarding claim 7, Peng specifically teaches PGE2 as treating ulcerative colitis (abstract; pg. 2, 1st full paragraph; pg. 9, 1st full paragraph).
Response to Arguments
In view of the amendments to the claims, the above rejections are new. However, arguments pertinent to the above rejection and those directed toward unexpected results are addressed.
On pgs. 8-9, Remarks, Applicant argues that an unexpected synergistic effect of revival stem cell induction was observed as disclosed in [0023] and Examples 1-3 of the specification.
This argument has been fully considered, but is not found persuasive. [0023] merely states,
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, which is not a showing of unexpected results.
Examples 1-3 state the following:
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. It is not clear how confirmation of induction of revival stem cell populations by melatonin and PGE2 is a showing of unexpected results.
On pg. 12, Remarks, Applicant argues that Example 1 and the results in Table 1, [0050] show an unexpected fold change between revival stem cell markers in the melatonin-PGE2 combined treatment group.
This argument has been fully considered, but is not persuasive to overcome the instant rejection. While the examiner agrees, that Table 1 shows a synergistic effect in fold change in claudin-4, clusterin, and Ly6a in response to a combination of melatonin and PGE2, in comparison to melatonin and PGE2, alone, this showing is not persuasive to show unexpected results since the instant claims are not limited to a composition or administering a composition comprising a combination of melatonin and PGE2; instant independent claim 1 recites a method of treating colitis by administering a composition comprising melatonin or 8m-PDOT and PGE2 or Cay10598, and instant independent claims 9 and 12 also recite such compositions or methods. Moreover, as argued by Applicants on pgs. 10, Remarks, “not all combinations of melatonin analogues and PGE2 receptor agonists induce revival stem cells.” Furthermore, the data in Table 1, [0050], does not show a method of treating colitis or provide correlative evidence that a fold change in revival stem cells of intestinal epithelial cells would treat colitis. And the data in Table 1 is limited to single concentrations of melatonin and PGE2, 500µm melatonin and 100nM PGE2, which is 0.1µM PEG2.
As such the data in Table 1 is not commensurate in scope to the instantly claimed methods.
Applicant is reminded that MPEP 716.02 states that unexpected results a) are greater than expected results, b) show superiority of a property shared with the prior art, c) exhibit the presence of an unexpected property, and/or d) exhibit the absence of an expected property. MPEP 716.02 additionally states that unexpected results must be commensurate in scope with the claimed invention and provide a comparison with the closest prior art.
Further, regarding the instantly claimed concentration ranges, Applicant is additionally reminded that to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960), See MPEP 716.02(d).
On pgs. 10-11, Remarks, Applicant argues that the revival cell limitations is not a mere “whereby” clause since the instant clause recites a non-inherent result, and since the specification shows that not all combinations of melatonin analogues and PGE2 receptor agonists induce revival stem cells. Applicant then points to a) a combination of PGE2 and 2-iodomelatonin, a melatonin analogue and b) treatment with butaprost, an EP2 receptor agonist to show that these compounds “did not show a specific induction effect” for revival stem cells, in contrast to a) Cay10598 which “showed an induction effect similar to or higher than that of PGE2.”
These arguments have been fully considered but are not found persuasive. It is respectfully pointed out that a) a combination of PGE2 and 2-iodomelatonin, a melatonin analogue and b) treatment with butaprost, would not be expected to have the same effects as the instantly claimed method since a combination of PGE2 and 2-iodomelatonin and b) butaprost are outside the scope of the instantly claimed method, which requires a composition comprising a) melatonin or 8M-PDOT, and PGE2 or Cay10598. As such, the combination of Cuzzocrea and Peng, which teaches a method of treating colitis by administering a composition comprising melatonin and PGE2, as instantly claimed, would be expected to have the effects recited in the instant “wherein” clauses, i.e., the wherein clauses express the desired result of the positive step of administering the composition melatonin and PGE2, to a patient with colitis, as taught by the combination of Cuzzocrea and Peng.
Applicant is further reminded that “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. . .’The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious,’” see MPEP 2145(II).
For these reasons, Applicant’s arguments are not persuasive to overcome the instant rejections.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
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