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 .
Election/Restrictions
Applicant’s election without traverse of Group V (claims 78 and 104) in the reply filed on 10/21/2025 is acknowledged. It is noted that upon the instant amendment, claims 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62 and 77, which were initially grouped as Group I, are now directed to the elected method of treating an allergy.
Applicant’s election of TNFSF10 as the interferon response gene is also acknowledged.
Claims 4-6, 8-15, 17-27, 29, 31-36, 38, 40-43, 63-76 and 78-109 have been canceled, and claims 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62 and 77 have been considered on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
The instant specification discloses SEQ ID NO:1 (para. [0065]-[0066]). However, applicant failed to file a sequence listing or Computer Readable Form (CRF).
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 2- are objected to because of the following informalities:
In claim 2, there should be a comma after “TNFS10” of (d) in line 8. It is also noted that the term “or” at the end of (c) should be after “d. TNFS10”. It appears that the term “TNFS10” in line 8 is typographical error. It would be “TNFSF10” instead. There should be a period after the letter “e” in line 9.
Claim 3 discloses “at least one of TNFSF10, CXCL10, or a combination thereof”. The term “at least one” and “a combination thereof” would be redundant. The limitation would be “at least one of TNFSF10 and CXC10”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 and 77 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 limitation directed to a population of antigen-specific CD154, CD137 or CD4 T cells. It is not clear if these markers are required to be positive or negative as the markers are not disclosed with regard to their expression. Clarification is required.
Claims 1 and 77 discloses “elevated expression level of an interferon response gene” or “elevated expression level of TNFSF10”. The term “elevated” is a relative term which renders the claim indefinite. The term “elevated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Clarification is required.
Claim 28 discloses “the TH1 group of Table 1”. MPEP§2173.05(s) states “[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).” Thus, the disclosure of “Table 1” in claim 28 does not particularly point out and distinctly claim the subject matter and thus, it renders the claim indefinite.
Claims 39 and 44 recite the limitation "the biological sample" in line 2 or line 1, respectively. There is insufficient antecedent basis for this limitation in the claim. Claim 39 is dependent on claim 37 which is dependent on claim 1, and claim 44 is dependent on claim 1. However, claim 1 or claim 37 does not disclose any biological sample. Thus, the limitation of claim 39 or claim 44 does not have a proper antecedent basis.
Claim 62 discloses that the method of claim 1 further comprising a step of incubating a biological sample or a population of T cells isolated from the subject comprising the antigen-specific CD154, CD137 or CD4 T cells with a TCR stimulator to generate a population of stimulated T cells prior to enriching or isolating the T cells. It is not clear how this additional step is related to the step of claim 1. Claim 1 discloses a step of administering a population of antigen-specific CD154, CD137 or CD4 T cells having the elevated expression of an interferon response gene. Is this population of T cells in claim 1 different from the antigen-specific CD154, CD137 or CD4 T cells stimulated with a TCR stimulator or the population of claim 1 is produced by the stimulating with the TCR stimulator? Are they two different population of CD154, CD137 or CD4 T cells utilized for the method? Clarification is required.
Furthermore, it is not clear if the limitation of “prior to enriching or isolating the T cells” requires a step of enriching or isolating the T cells.
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 and 77 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 instant claims disclose a method of treating an allergy by administering an antigen-specific CD154, CD137 or CD4 T cells expressing elevated amount of interferon responsive genes.
The scope of antigen-specific CD137, CD154, CD4 T cell with elevated amount of interferon responsive genes is broad. The “antigen” is not particularly limited and thus, the scope of antigen is extensive. It is noted that claim 16 limits the antigen to HDM, and the specification discloses HDM-reactive T cells a sole example of antigen-specific CD137, CD154, CD4 T cells identified from the comparison of HDM-reactive allergy with or without asthma.
The claims disclose that the method would generally treat an allergy without limiting to a specific allergy using antigen-specific T cells obtained from any source (i.e. autologous, allogeneic or xenogeneic) or the type of antigen without being limited (e.g. any inflammation in skin, airway mucosa, atopic dermatitis, allergic rhinitis, allergic asthma, allergic conjunctivitis or any pathogenic infection).
However, the instant specification does not provide sufficient written description with regard to the genus of allergy which is based on different allergens as the specification only discloses studies and data based on house dust mite (HDM) triggered allergic reaction and associated asthma, and the antigen-specific T cells being HDM-specific T cells.
There is no other disclosure with regard to any other allergy caused by different allergens or any pathogenic infection in terms of generating the claimed cells. There is no indication that the identified THIFNR cells or TregIFNR cells would apply to any allergic reaction or pathogenic infection in a subject.
The instant specification defines the term “treating” or “treatment” of a disease in a subject as (1) preventing the symptoms or disease from occurring in a subject that is predisposed or does not yet display symptoms of the disease; (2) inhibiting the disease or arresting its development; or (3) ameliorating or causing regression of the disease or the symptoms of the disease. Thus, the scope of the instant claims intended for “treating” an allergy in a subject would encompass prevention of an allergy from occurring in a subject, inhibiting or ameliorating the allergy. It is understood that based on the definition given, the scope of “treating” does not include curing.
There is no showing of any results produced by the claimed treatment of any allergy, let alone HDM-reactive allergy, in the instant specification. There is no evidence supporting that the claimed method would necessarily and sufficiently produce the prevention encompassed by the scope of the “treating”. The instant specification discloses that the T cells expressing elevated level of TRAIL or TNFSF10 would suppress inflammation, and this is based on ex vivo experimentations that TRAIL inhibited TCR-dependent activation of TH cells (para. 367).
However, the instant specification fails to provide any evidence that these specific subset of T cells would necessarily and sufficiently treat any allergy in vivo and even if it does, the specification does not provide any detailed embodiment for the claimed cells to generate desirable or therapeutically effective outcome in treating an allergy.
At most, it is only expected that the claimed TH or Treg cells would be helpful in alleviating symptoms or inflammation based on the expression of TRAIL, but this does not support for the “prevention” encompassed by the “treating”.
It is understood that the claimed cell population is a subset T cell population found in the non-HDM allergic subject having HDM-reactive T cells with an elevated expression level of an interferon response gene or TRAIL-expressing T cells (THIFNR cells and TregIFNR cells) compared to subjects with HDM allergy and asthmatic subject without HDM allergy. As discussed above, there is no disclosure in the instant specification showing the claimed TH cells or Treg cells in a method of “treating” any allergy, and the disclosure of the specification is limited to TH cells or Treg cells specific for HDM. There is no other “antigen”-specific T cells disclosed in the instant specification. The specification provides a potential benefit of the claimed cells but there is no showing if these cells would actually treat any allergy and even prevention of developing allergy.
The source of the antigen-specific CD154, CD137 or CD4 T cells of the instant claims is disclosed as any biological sample from a subject (claim 1) or a subject suspected of suffering from an inflammation of the skin, airway mucosa, atopic dermatitis, allergic rhinitis, allergic asthma, allergic conjunctivitis or a pathogenic infection (claim 48). This appears to be based on the assumption that there would be an antigen-specific TH or Treg cells or CD137+, CD154+ or CD4+ T cells having elevated interferon response gene. However, it is not known in the art that the claimed cells are indeed present in any subject or those subject having allergies or pathogenic infection. Thus, while the claimed cells are shown to be present in the subject having HDM-reactive allergy, and there is a subset of TH cells expressing elevated interferon response gene in the subject having HDM-reactive allergy and asthma according to Tibbitt et al. (2019, Immunity), however, the instant specification fails to provide sufficient written description for the entire scope of the claimed invention with regard to the source of the claimed cells.
While the identification of subsets of TH cells known in the subject having HDM-reactive allergy and associated asthma according to Tibbitt et al. (2019, Immunity) including those with elevated expression of interferon response gene, however, there is no known or suggested functionality of the subset of TH cells that expresses interferon response gene in any allergic reaction to support the claimed method, particularly for the prevention of allergy.
There is no known therapeutic treatment in the art at the time of filling to prevent allergy other than alleviating or reducing the symptoms by using antihistamines, corticosteroids and or leukotriene inhibitors or preventing the exposure to the allergen (see Paris et al. 2021, Pharmaceutics). However, there is no known effective cell based therapy in the art at the time of filing. Furthermore, the specification does not provide any working example that the claimed cells are sufficiently and necessarily treat any allergy including preventing thereof. While it is expected that alleviation of allergic symptoms due to the Treg cells’ immunosuppressive role known in the art, and thus, it is also expected that they might be alleviating allergic reaction, however, there is no expectation that the claimed cells would successively prevent the onset of allergy.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.” and further, “The description needed to satisfy the requirements of 35 U.S.C. 112 "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.< Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art. In most technologies which are mature, and wherein the knowledge and level of skill in the art is high, a written description question should not be raised for claims >present in the application when originally filed,< even if the specification discloses only a method of making the invention and the function of the invention. See, e.g., In re Hayes Microcomputer Products, Inc. Patent Litigation, 982 F.2d 1527, 1534-35, 25 USPQ2d 1241, 1246 (Fed. Cir. 1992) ("One skilled in the art would know how to program a microprocessor to perform the necessary steps described in the specification. Thus, an inventor is not required to describe every detail of his invention. An applicant's disclosure obligation varies according to the art to which the invention pertains. Disclosing a microprocessor capable of performing certain functions is sufficient to satisfy the requirement of section 112, first paragraph, when one skilled in the relevant art would understand what is intended and know how to carry it out."). In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.”
Claims 1-3, 7, 16, 28, 30, 37, 39, 44-45, 48, 59, 62 and 77 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for alleviating allergy by administering HDM-reactive THIFNR or TregIFNR cells, does not reasonably provide enablement for preventing allergy. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The instant claims disclose a method of treating an allergy by administering an antigen-specific CD154, CD137 or CD4 T cells expressing elevated amount of interferon responsive genes. It is understood that these cells are CD154+, CD137+ or CD4+ T cells with elevated amount of interferon responsive genes or THIFNR or TregIFNR cells.
The scope of the term “treating” is broad to encompass not only suppressing or alleviating symptoms of allergic reaction but also preventing any allergic reaction in any subject.
The instant specification defines the term “treating” or “treatment” of a disease in a subject as (1) preventing the symptoms or disease from occurring in a subject that is predisposed or does not yet display symptoms of the disease; (2) inhibiting the disease or arresting its development; or (3) ameliorating or causing regression of the disease or the symptoms of the disease.
Thus, the scope of the instant claims intended for “treating” an allergy in a subject would encompass prevention of an allergy from occurring in a subject based on the definition (1) above.
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 treating an allergy.
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 functions that 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 evidence supporting that these cells would be sufficient enough to prevent any allergy in a subject. Considering the broad scope of “treating” encompassing “preventing”, the lack of any showing in the instant specification with regard to the functionality of the claimed cells in preventing allergic reaction would require undue experimentations for the claimed scope. It is highly unpredictable if any therapeutic composition would be able to prevent innate allergic reaction unless such inherent mechanism is abolished in the subject. While it is plausible that the TRAIL expressing cells would provide a beneficial effect in alleviating the allergic reaction, however, there is no known means to “prevent” allergic reaction in the art. Even the instant specification fails to provide any evidence to support the entire scope of the treating encompassing prevention.
Conclusion
No claims are allowed.
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