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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/09/2026 has been entered.
Claim Status
Applicant’s reply filed on 06/09/2026 is acknowledged. Claim 12 is newly added.
Claims 1, 3, 5, 7-8, 11-12 are pending and under examination.
Rejections Maintained
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.
Claims 1, 3, 5, 7-8, 11 and newly added claim 12 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Faget (US9376493B2, published 06/28/2016, PTO-892 07/15/2025) in view of Querfeld (Cancer Immunol Res. 2018 Aug;6(8):900-909) and Mehra (JAMA Dermatol. 2015 Jan;151(1):73-7, PTO-892 07/15/2025).
The disclosure of Faget is directed to antibodies directed against ICOS which inhibit ICOS and ICOS-L interactions (see Abstract). The disclosure of Faget originates from the same inventive entity of the instant application and discloses the generation and characterization of the anti-ICOS monoclonal antibodies of the instant application (Pg. 23, Column 23, Paragraph 3).
Regarding claim 1, pertaining to a method of treating cutaneous T cell lymphoma (CTCL) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-ICOS antibody, Faget discloses the following limitations:
Anti-ICOS monoclonal antibodies deposited at the CNCM under the accession numbers CNCM I-4176, CNCM I-4177, CNCM I-4178, CNCM I-4179, and CNCM I-4180 and their corresponding CDR sequences (Pgs. 13 and 14).
A method of treatment of a patient in need comprising administering an anti-ICOS antibody of the disclosure, wherein the patient has a human malignant lymphoma (Faget claims 3 and 4)
The disclosure of Faget does not disclose (1) the subject in need has Sézary syndrome or (2) the antibody is conjugated to a cytotoxic moiety.
These deficiencies are taught by Querfeld and Mehra.
Querfeld:
The disclosure of Querfeld is directed to the evaluation of immune checkpoint expression as a marker of T cell dysregulation across the continuum of CTCL disease stages to guide the use of checkpoint inhibitors in the treatment of CTCL (Pg. 901, Left column, Full paragraph 2, Lines 8-13).
Regarding claims 1 and 3, wherein the CTCL is Sézary syndrome, Querfeld compared mRNA expression between early-stage mycosis fungoides and advanced-stage mycosis fungoides/Sézary syndrome and determined that the more advanced disease state displayed higher expression of immune checkpoint genes, including ICOS (Fig. 3B). Querfeld concludes the data of the disclosure provides a rationale for immune checkpoint inhibition to reverse T cell exhaustion in the treatment of disease (Pg. 907, Right column, Full paragraph 1, Lines 17-23).
Mehra:
The disclosure of Mehra is directed to a report of three patients with mycosis fungoides and one patient with Sézary syndrome who were treated with brentuximab vedotin, a conjugate of an anti-CD30 antibody and MMAE (Abstract, Importance section).
Regarding claims 1, 5, 7, 9 and 11-12, wherein the antibody is conjugated to the antimitotic agent MMAE, Mehra teaches administration of the anti-CD30/MMAE conjugate to patients (Pg. 73, Right column, Paragraph 1). Mehra teaches that brentuximab vedotin treatment was an effective neoadjuvant treatment in two patients, reducing the disease burden and enabling allogenic stem cell transplantation.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to use the anti-ICOS antibodies of Faget (1) in a method to treat Sézary syndrome and (2) conjugated to antimitotic agent MMAE. One would have been motivated to do so because (1) Querfeld teaches ICOS expression is upregulated in Sézary syndrome indicating the potential for anti-ICOS treatment to reduce the exhausted phenotype found in advanced CTCL and (2) Mehra teaches the antitumor effects of an antibody-drug conjugate comprising a CTCL antigen antibody conjugated to MMAE. There would be an expectation of success in using the antibodies as part of an antibody-drug conjugate as taught by Mehra in a method to treat Sézary syndrome as taught by Querfeld because Mehra teaches the efficacy of targeting Sézary syndrome with an antibody-drug conjugate comprising MMAE and Querfeld teaches that ICOS is upregulated in Sézary syndrome and would thus be a suitable therapeutic target.
Declaration Under 37 C.F.R §1.132 of Daniel Olive
The declaration under 37 CFR 1.132 filed 06/09/2026 is insufficient to overcome the rejection of claims 1, 3, 5, 7-8, and 11-12 based upon 35 U.S.C 103 as set forth in the last Office action.
The declaration provides the following arguments:
I. There would be no reasonable expectation of success in combining the cited references to arrive at the claimed invention. While Querfeld mentions that ICOS expression is increased in mycosis fungoides and Sezary syndrome, Querfeld also teaches that other immune checkpoint receptors are upregulated such as CTLA-4, LAG3, and PD-I. However, administration of antibodies against other immune checkpoint receptors such as PD- I have had limited success for the treatment of mycosis fungoides and Sézary syndrome (Declaration, Pg. 1).
In response, the data regarding ineffectiveness and lack of safety of targeting PD-1 in the claimed cutaneous T cell lymphomas does not have a direct bearing on the expectation of success in targeting ICOS with an antibody drug conjugate because PD-1 is an inhibitory checkpoint molecule and ICOS is a stimulatory checkpoint molecule. On the contrary, there would not be an expectation that targeting ICOS would enhance malignant T cell activation because ICOS is not in inhibitory receptor. PD-1 and ICOS further diverge in that they have different expression profiles. Kim (Front Cell Dev Biol. 2021 Nov 22;9:767466) teaches that PD-1 is expressed on various cell types including CD8+ T cells, Tregs, B cells, NK cells and myeloid cells (see Table 1), whereas ICOS expression is restricted to activated T cells.
Importantly, the rationale of targeting ICOS also exists independent of the checkpoint mechanism of ICOS, as it is was known at the time of filing that ICOS expression is associated with cutaneous lymphomas. For example, Bosisio (Am J Dermatopathol. 2015;37(2):115-121, IDS filed 11/11/2022) teaches ICOS expression is upregulated on the surface of malignant T cells in patients with mycosis fungoides. This alone provides a rationale for targeting cells that express ICOS (Abstract).
II. The technology of the instant invention is based on an antibody-drug conjugate (ADC), in which the anti-ICOS antibody serves primarily as a highly selective delivery vehicle for a cytotoxic payload directly into ICOS-expressing malignant T cells (Declaration, Pg. 3).
In response, though the mechanisms by which monoclonal antibodies and antibody drug conjugates target malignant cells differs, the goal of targeting and inhibiting malignant cell types is the same. In fact, antibody drug conjugates have a preferable profile in that they selectively deliver the toxic payload directly to the target cancer cells (Reviewed in Chau, Lancet. 2019 Aug 31;394(10200):793-804). Chau teaches the use of CD30-MMAE ADC in mycosis fungoides, (Table 1, Pg. 797) pointing to reasonable expectation of success in targeting malignant cells using antibody drug conjugates in the context of cutaneous T cell lymphomas.
III. The extent of therapeutic efficacy obtained with our ICOS ADCs was unexpected. In the preclinical studies of the instant applicants, anti-ICOS ADCs induced profound and durable antitumor responses in highly aggressive ICOS-positive patient-derived xenograft (PDX) models of AITL (a TFH-derived lymphoma) (Declaration, Pg. 4).
In response, the evidence provided is not commensurate with the scope of the claims and therefore do not constitute unexpected results. The claims are directed specifically to mycosis fungoides and Sezary syndrome, while the data provided is in the context of a xenograft model of Angioimmunoblastic T-Cell Lymphoma.
For these reasons, the declaration of Dr. Daniel Olive is not sufficient to overcome the 35 U.S.C. 103 rejection.
Response to Applicant’s Remarks
All remarks are addressed in the response to the Declaration under 37 CFR 1.132 above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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