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 . 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.
Election/Restrictions
Applicants elected treating IBD with SEQ ID 25 without traverse in the reply filed on 30 May, 2025. In the response of 15 Dec, 2025, applicants amended their claims so they no longer read on applicant’s elected species (SEQ ID 28 has 63% identity with SEQ ID 25). Following Markush practice, this is treated as if the elected species was found allowable, and the search expanded to the independent claim. The search is stopped when (a) reference(s) are found that anticipate or render obvious that claim.
Claims Status
Claims 13-15, 30, and 31 are pending.
Claim 13 has been amended.
Claims 30 and 31 are new.
Claims 30 and 31 have been withdrawn due to an election/restriction requirement.
Withdrawn Objections
The objection to claims 16 and 23 as duplicates is hereby withdrawn due to amendment.
Withdrawn Rejections
The rejection of claims 13-19 and 23-25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to uncertainty as to what constitutes a serpin A3 protein is hereby withdrawn due to amendment.
The rejection of claims 18 and 24 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to the requirement for the therapeutic to be both a fragment and a full length polypeptide is hereby withdrawn due to amendment.
The rejection of claim(s) 13-19, 21, 23-25, and 27 under 35 U.S.C. 102(a)(1) as being anticipated by Lezdey et al (US 5,008,242, is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(a)
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 13-15 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.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure(MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure and (d) representative number of samples.
The issue is which mutated variants of Serpin A3 will be effective for applicant’s invention.
a and b) actual reduction to practice and disclosure of drawings or structural chemical formulas: Applicants used SEQ ID 28 (mouse serpin A3) with a His tag (p31, line 33-34). There is no discussion, save for language that mirrors the claim language, of modifications of the native sequence and homologs.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure: Applicants are claiming a method of treating IBD, in some claims with a limitation of promoting growth or suppressing decrease of mesenchymal stem cells. This requires that the material have a beneficial effect in IBD, with some claims requiring that the beneficial effect be mediated by MSCs, a functional limitation of the material. However, applicants have not stated where the native serpin A3 can be modified and maintain activity. An artisan in this field would not know what sequence/hydrophobicity/tertiary structure is required to provide a benefit in IBD. In essence, applicants have defined a critical part of their invention by function. That is not sufficient to meet the written description requirement.
The Uniprot database entry for serpin A3 (downloaded 9 June, 2025) shows that the protein is known to bind to a number of different proteins (8th page, section “interaction,” continues to 9th page). There are also a very large number of known variants of the protein; most of which have unknown clinical significance (16th and 17th pages).
Even if we knew what protein the serpin A3 bound to cause the desired effects, as of applicant’s priority date, it was not possible to predict if a given molecule bound to a receptor. Lowe (blog “In the pipeline” entry of 7 Sept, 2022) describes an experiment where that was attempted. 39K compounds, including known antibiotics, were screened against E. coli for growth inhibition, finding 218 active compounds (1st page, 3d paragraph). These were computer docked to a set of 296 essential bacterial proteins by multiple docking procedures (1st page, 3d paragraph), along with 100 random inactive compounds (2nd page, 1st paragraph). The number of strong binders predicted were essentially the same between the active compounds and the controls, and out of 142 compound/target interactions previously known, the methodology found only 3 (2nd page, 2nd paragraph). While a given docking program may accurately predict if compound A binds to protein B, it is impossible to a priori know if the prediction is accurate. In other words, several years after applicant’s priority date, it was not possible to predict if a given mutant and target protein to each other.
Nor is it possible to modify known sequences to reliably find new compounds. Guo et al (PNAS (2004) 101(25) p9205-9210) looked at the effect of random mutations (title). In a DNA repair enzyme, about one mutation in three killed the activity of the protein, consistent with studies with other proteins (abstract). Yampolsky et al (Genetics (2006) 170 p1459-1472), using a different methodology, found that even conservative substitutions were prone to problems (table 3, p1465, top of page). In other words, unless there is some information known about the binding, mutating the sequence is likely to be detrimental, making it a poor way to generate new compounds.
(d) representative number of samples:
All of applicant’s examples used the native sequence for the animal treated. Given that no one knows what the material binds with to cause the effects required by the claims, and that random mutations have a high probability of inactivating the polypeptide, an artisan in this field cannot extrapolate from the single sequence used by applicants to all possible sequences. Thus, the claims lack written description.
response to applicant’s arguments
Applicants argue that they have amended around this rejection, and reference SEQ ID 28.
Applicant's arguments filed 15 Dec, 2025 have been fully considered but they are not persuasive.
The issue is that the claims allow for variability in the sequence, but it is not known how the sequence can be modified and maintain activity. Claims 13-15 still allow for 95% identity to SEQ ID 28, so the issue remains. SEQ ID 28, as a known sequence, would not have the issue (so claim 31, if rejoined, would not have the issue). However, 95% identity with SEQ ID 28 is an issue.
New Rejections
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) 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lezdey et al (US 5,008,242, cited by applicants), in view of Wirtz et al (Adv. Drug Deliv. Rev. (2007) 59 p1073-1083), with evidentiary support from Koning et al (Front. Immunol. (2013) 4(49), previously cited).
Lezdey et al describe using alpha1 antichymotrypsin to treat inflammation (abstract). This includes inflammatory bowel diseases (column 1, line 68, continues to column 2, line 1), applicant’s elected disorder, and includes humans and other mammals as patients (column 1, line 62), a genus that includes mice.
The difference between this reference and the examined claims is that this reference does not explicitly discuss the mouse homolog of the protein.
Wirtz et al discusses mouse models of inflammatory bowel disease (title). These are indispensable for our understanding of the pathogenesis of these disorders (abstract). This reference discusses mice with IBD.
Therefore, it would be obvious to treat the mice of Wirtz et al with the alpha 1 antichymotrypsin of Lezdey et al, to treat the disorder and to investigate how it interacts with the disease. As Lezdey et al describes a genus that includes mice, an artisan in this field would attempt this therapy with a reasonable expectation of success.
Lezdey et al teach alpha 1 antichymotrypsin to treat IBD. Wirtz et al render obvious using the therapy on mice, which reasonably would use a mouse homolog. SEQ ID 28 is the mouse homolog minus the first 20 AAs, for (398/418=)95.2% identity. This is the same therapy for the same disease, so it will necessarily produce the same result. Alternatively, as evidenced by Koning et al, inflammation will draw MSCs from the bone marrow (title), so a therapy that will reduce inflammation will reduce the decrease of bone marrow MSCs drawn off by inflammation. Note this is the same effect that applicants state that they have observed (p34 line 1-4). Thus, the combination of references renders obvious claims 13-15.
response to applicant’s arguments
While this is a new rejection, it closely follows a withdrawn rejection, and applicant’s arguments with respect to that rejection apply. In the interest of compact prosecution, those arguments are answered here.
Applicants argue that Lezdey et al does not mention stem cells, and that Koning et al is limited to models of MS.
Applicant's arguments filed 15 Dec, 2025 have been fully considered but they are not persuasive.
The rejection treats the same patients with the same drug, which will necessarily have the same results. The fact that the reference does not mention those results does not change that.
Applicants argue that the conclusions of Koning et al are limited to a mouse model of MS. However, the title of the reference is “Mesenchymal stem cells are mobilized from the bone marrow during inflammation.” In other words, the authors of the paper made the conclusion that applicants state is not valid. Unless applicants have persuasive evidence that the conclusion is misguided, their belief that this is an untoward extrapolation from the reference is not sufficient to overcome the rejection.
Conclusion
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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658