DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's amendment and remarks filed on 02/27/2026 are acknowledged.
Claims 1, 3-13, 15-19 and 23 are pending.
Claims 16-19 and 23 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/16/2025.
Claims 1, 3-13 and 15 are presently under consideration.
3. Claim interpretation.
The recitation of “an antigen on a cell associated with a disease and/or disorder associated with inflammation in the subject” in claim 1 reads on antigens present on the specified cells and any other cells, such as antigens common to all cells.
The recitation of “a non-activating antigen of a T cell” in claim 1 reads on non-activating antigens present on any type of T cells and any other cells, such as antigens common to all cells.
4. 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.
5. Claims 1, 3-13 and 15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite in the recitation of a cell “associated with” disease and/or disorder associated with inflammation in the subject, because neither the nature nor the degree of “association” is defined. Applicant does not appear to have addressed the grounds of rejection presented in subsection 6(iii) of the previous office action, which are therefore maintained for the reasons of record.
(ii) Claim 4 is indefinite in the recitation of “the antigen,” because it is unclear whether it refers back to “an antigen on a cell associated with a disease and/or disorder associated with inflammation in the subject,” or to “a non-activating antigen of a T cell,” recited in claim 1.
(iii) Claim 4 is further indefinite because of the following inconsistencies:
Method step (a) comprises “isolating peripheral blood mononuclear cells comprising a population of T regulatory cells (TREGS) from a subject,” and method step (b) comprises arming “the population of T regulatory cells (TREGS) with the bispecific antibody (BiAb) to produce ATREGs.” It is unclear how arming of Treg cells specifically is achieved within the population of peripheral blood mononuclear cells, of which Tregs constitute only a minor fraction. It is further unclear how arming of Tregs produces “activated” Tregs, in the absence of an activation step.
Subclause (b)(i) states that “generation of T regulatory cells (TREGS) occurs,” which is in contradiction to step (a), which specifies that Tregs were already present in the population peripheral blood mononuclear cells.
Subclause (b)(ii) states that “the BiAb arms the TREGS to produce the activated regulatory T cells (ATREGs),” which is in contradiction to claim 1, which specifies that the BiAb “binds to a non-activating antigen of a T cell,” i.e. arming of Tregs with the BiAb does not activate Tregs.
(iv) Claim 7 is indefinite as being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 803.02.
(v) Claim 7 is further indefinite because of the following inconsistencies:
The claim recites an embodiment of inducing TREGs by ex vivo stimulation with a checkpoint inhibitor antibody which, in the absence of at least TCR stimulation, is not expected to “induce” Tregs, as a person of skill in the art would be aware.
The claim also recites an embodiment of “inducing” the TREGs” [of claim 4] “by an in vivo treatment of the subject with a checkpoint inhibitor antibody.” The Tregs of claim 4 are already armed with BiAbs and administered to the subject per claim 1, therefore, it is unclear how they can be further “induced.”
(vi) Claims 3-13 and 15 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
6. The following is a quotation 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.
7. Claims 1, 3-13 and 15 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contain(s) subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method of treating a disease and/or disorder associated with inflammation
The specification does not enable one of skill in the art to make and use the invention as claimed without undue experimentation. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
(i) The claimed method is directed to treating inflammation by targeting Tregs to the inflamed tissue by means of bispecific antibodies with one arm binding to Tregs and another arm binding to an antigen specific to the inflamed tissue.
As noted in section 3 above, the claims, as presently recited, read on bispecific antibodies binding to antigens which are not limited to inflamed tissues or to regulatory T cells. Such antibodies are would not target Tregs to sites of inflammation, and therefore practicing the invention as claimed will not result in any disease being “treated.” Therefore, an ordinary artisan would reasonably conclude that practicing the method as claimed be unsuccessful, and consider experimentation to that end to be unnecessary, improper, and undue.
(ii) IF the claims were limited to bispecific antibodies specific to an antigen present only in an inflamed tissue and to an antigen present only on regulatory T cells, the specification may be enabling for a method of treating Type 1 diabetes, organ graft rejection, and graft-vs-host disease, but not for a method of treating a generically recited “disease and/or disorder associated with inflammation,” or a generically recited autoimmune disease.
[It is emphasized that in pointing out the potentially enabled embodiments of the invention, the Examiner has not made a determination as to whether such language would constitute New Matter under 35 USC 112(a).]
To make antibodies specific to an antigen present only in an inflamed tissue, a person of skill in the art has to know the identity of at least one such antigen. As noted in section 10 of the previous office action, such antigens are known for Type 1 diabetes (Tenspolde et al., 2019, of record, p. 8) and certain instances of graft rejection (Id, p. 9), but not for other inflammatory conditions. Since the instant specification does not appear to provide guidance, direction, or working examples of such antigens, a skilled artisan would have to discover antigens specific to inflamed tissues in the multitude of diseases and disorders encompassed by the breadth of the claims.
Accordingly, the entire scope of experimentation required to develop methods commensurate with the scope of the claims is left to those skilled in the art, the present claims and disclosure amounting to nothing more than an invitation to the skilled artisan to invent such methods.
8. 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 of this title, 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.
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.
9. Claims 1, 3-5, 7-13 and 15 stand rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Jaume et al. (US 20220008522), Trabolsi et al. (2019), and Prabhakar et al. (US 20130236464) (all of record).
The grounds of rejection presented in section 12 of the previous office action are maintained essentially for the reasons of record, as they apply to the amended claims.
Applicant’s arguments have been fully considered but have not been found convincing. Applicant points out the differences between the claims and the teachings of each of the cited prior art references. In response, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references (MPEP 2145).
To recap, the presently claimed method involves targeting Tregs to inflamed tissue by means of a bispecific antibody specific to Tregs and to inflamed tissue. Jaume teaches targeting Tregs to pancreatic cells in diabetes by means of chimeric receptor specific to pancreatic cells, Trabolsi reviews multiple examples of targeting T cells to various tissues by means of bispecific antibodies, and Prabhakar teaches a bispecific antibody to CTLA-4 on Tregs and to GLUT2 on pancreatic cells for treatment of diabetes.
Therefore, the rejection is maintained, and is incorporated by reference herein as if reiterated in full.
10. Claims 1 and 6 stand rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Jaume et al. (US 20220008522), Trabolsi et al. (2019) and Prabhakar et al. (US 20130236464), further in view of Schmidt et al. (2016) (all of record).
The grounds of rejection presented in section 13 of the previous office action are maintained essentially for the reasons of record, as they apply to the amended claims. Applicant’s arguments and examiner’s reply are essentially the same as addressed in section 9 above.
11. Conclusion: no claim is allowed.
12. 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.
/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
Prosecution Insights