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 .
Applicant’s amendment and response filed on 7/1/2026 has been received and entered into the case.
Claims 4-6, 8-15, 17-27, 29, 31-36, 38, 40-43, 63-76 and 78-109 have been canceled, claim 110 is newly added, and claims 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62, 77 and 110 have been considered on the merits. All arguments have been considered.
Claim Objections
Claims 2, 7, 16, 28, 30 are objected to because of the following informalities: These claims disclose the verb, i.e. “comprise” or “are” which is inconsistent with the subject of “the population”. It should be “comprises” or “is” instead. Appropriate correction is required.
Claim Rejections - 35 USC § 112 (New 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 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62, 77 and 110 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.
Claim 1 and its dependent claims disclose a method of alleviating an allergy by administering an allergen-reactive CD4+ T cells expressing elevated amount of TNFSF10 or CXCL10.
Claim 77 discloses a method of alleviating an allergy by administering an HDM-reactive or aspergillus fumigatus-reactive CD4+ T cells expressing elevated amount of TNFSF10 or CXCL10.
It is understood that these cells are CD4+ T cells with elevated amount of interferon responsive genes or THIFNR or TregIFNR cells.
The scope of “allergen” in claim 1 and its dependent claims is extremely broad, and any protein that is a target of IgE antibody response in a subject and the instant specification discloses examples of the allergens including an aeroallergen such as dust mite, mold, and a pollen; a food allergen such as milk, egg, soy, wheat, nut, or fish protein; an allergen from a pet or a pest; or an allergen from a drug (para. 64).
Thus, the claimed “allergen” is extremely broad and the claimed invention would necessarily alleviate any allergy with CD4+ TH cells reactive to any allergen. The scope encompasses not only the CD4+ TH cells reactive allergen responsible for a specific allergy (e.g. HDM reactive CD4+ TH cells for asthma or airway inflammation caused by HDM) but also for alleviating other allergy with the CD4+ TH cells reactive to unrelated allergen (e.g. HDM reactive CD4+ TH cells for peanut allergy).
Thus, the instant claims are interpreted that administering CD4+ TH cells reactive to any allergen would alleviate any allergy known in the art. In other words, at least CD4+ TH cells are reactive to any allergen, these cells can alleviate any allergy regardless the allergen.
Similarly, claim 77 is interpreted such that administering HDM-reactive or aspergillus fumigatus-reactive CD4+ TH cells would necessarily alleviate any allergy.
The instant specification discloses the identification of different proportion in the subsets of allergen-reactive T cells in HDM allergic and non-allergic subjects, and the finding of HDM-reactive TH cells expressing the interferon response signature (THIFNR, cluster 4) in subjects without HDM allergy (Example 1; para. 311), and CXCL10 and TNFSF10 are highly expressed in these THIFNR subset. Similarly, HDM-reactive Treg cells are proportionally higher in asthmatic subjects without HDM allergy. Based on these findings of preferential expansion of HDM-reactive Treg and TH cells expressing the interferon response signature in asthmatic subjects without HDM allergy, these cells are claimed for alleviating an allergy. The instant claims also disclose another allergen, Aspergillus fumigatus (ASP), and the specification discloses that THIFNR cells against ASP, and alleged that the THIFNR cells can be generated against other common allergens. However, these examples are limited to the specific allergens, HDM and ASP, and the production of THIFNR cells reactive to HDM or ASP.
The suppression of allergic reaction by Treg cells is known in the art as the suppressive function of Treg cells are essential to control autoimmunity, allergic and inflammatory reactions and responses to infectious agents and tumors according to Rivas et al. (2017, J. Allergy Clin. Immunol.). Rivas et al. teach that The Treg cells have “dual” functionality in allergic diseases that they are essential in promoting tolerance to allergens but also a pro-allergic inflammatory environment can skew these cells toward a pathogenic phenotype that aggravates and perpetuates diseases (Abstract).
According to the instant specification, the expression on TRAIL by these cells would be beneficial for suppressing inflammation caused by allergens according to the instant specification. However, Weckmann et al. (2007, Nature Medicine) show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways and attenuated homing limits TH2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6 (p.1309, 2nd col.). Weckmann et al. teach that recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells (Abstract). Rather, TRAIL is causing airway hyperreactivity (AHR) and inflammation (p.1311, 2nd col.), a characteristics of allergic asthma. This teaching appears to contract the role of TRAIL in suppressing inflammation.
Based on the above discussion, it is known in the art that Treg cells or TRAIL would have dual functions such that one of the dual functions might contradict the alleged therapeutic efficacy in treating allergy. Even if the effect of the TRAIL expressing THIFNR and TregIFNR cells of the claimed invention indeed produce a therapeutic benefit in reducing inflammation, however, there is no sufficient written description supporting that these allergen-reactive, or HDM-reactive, TH cells or Treg cells would be sufficient enough to alleviate any allergy in a subject, and thus, it is highly unpredictable if the TH or Treg cells reactive to any allergen or those cells reactive to HDM are capable of alleviate any allergy regardless the allergen considering the potentially contradicting function of the TRAIL expressed by THIFNR or TregIFNR.
Even if the allergen is limited to HDM as in claim 77, the instant specification fails to provide sufficient written description that this HDM-reactive TH cells or Treg cells would be able to alleviate any allergy as claimed.
The instant specification discloses example having HDM-reactive TH or Treg cells to alleviating allergy caused by HDM, and there is no other description that these HDM-reactive TH or Treg cells can alleviate allergy caused by other types of allergens.
Thus, it is the Examiner’s position that the instant specification fails to provide sufficient written description to show that the inventors had possession on the entire scope of the claimed invention.
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.
Claims 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62, 77 and 110 are 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.
Claim 1 discloses the wherein clause of “the elevated expression level of TNFSF10 or CXCL10 is increased relative to a corresponding T cell not stimulated with the allergen.” It is not clear if this intends to point out that the “elevated expression level” is increased further, or the “expression level” in the T helper cells or T reg cells is increased. Clarification is required.
Claim 16 discloses the wherein clause directed to the population of allergen-reactive T helper cells or Treg cells comprise aero-allergen-reactive. It appears that the wherein clause was not finished and a term after “aero-allergen-reactive” missing (e.g. T helper cells or Treg cells). If not, the clause should be “is aero-allergen-reactive” instead. Without the additional limitation, the claim is considered indefinite. Clarification is required.
Claim 39 discloses “the population” and the claim is dependent on claim 37. Claim 37 discloses two “population”: “population of allergen-reactive T helper cells or Treg cells” or “enriched population of allergen-reactive T helper cells or Treg cells”. It is not clear what the term “the population” of claim 39 is intended to point out.
Claim 48 discloses that the biological sample is obtained from a subject suffering from the listed species. The species listed in claim 48 does not contain any conjunction, i.e. “and” or “or”. It is not clear if the biological sample is from the subject having all the condition or the species is alternative. Clarification is required.
Claim 59 discloses that the biological sample is further stimulated with an HDM peptide or aspergillus fumigatus that is specifically recognized and bound by the allergen-reactive CD4 positive T helper cells or Treg cells. It is not clear how the allergen-reactive CD4 positive T helper cells or Treg cells recognize and bind to the HDM peptide or aspergillus fumigatus unless these cells are reactive to these allergen. In other words, the cells reactive other allergen are not able to recognize and bind to HDM peptide or aspergillus fumigatus. Clarification is required.
The term “the population of allergen-reactive T helper cells or Treg cells” in lines 1-2 of claim 110 does not have antecedent basis for the phrase. Claim 110 is dependent on claim 77 and refers to the “allergen-reactive” cells. However, claim 77 does not disclose “allergen-reactive” cells.
Response to Arguments
Applicant’s arguments with respect to the instant amendment have been fully considered and are persuasive. The claim rejections under 35 U.S.C. 112(a) and 103 have been withdrawn.
It is noted that a new 112(a) written description rejection is presented above due to the instant amendment.
The instant amendment necessitated a new 112(b) rejection as presented above.
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 TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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