CTNF 18/043,554 CTNF 82602 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 the species represented by a chemotherapeutic in the reply filed on 05/13/2026 is acknowledged. Claims 66, 67, 72, 148-164 are pending; claims 160-161 are withdrawn from prosecution as being drawn to non-elected species. Claims 66, 67, 72, 148-159, and 162-164 are examined. Information Disclosure Statement The information disclosure statements (IDS)s submitted on 07/20/2023 and 01/06/2025 were considered by the examiner. 06-49-06 AIA 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 Rejections - 35 USC § 112 07-36 AIA The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 67 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The claim depends of claim 66, which is drawn to an antibody or antigen-binding fragment comprising: a heavy chain variable (V H ) region of a CD138-binding antibody; (b) a light chain variable (V L ) region of the CD138-binding antibody; and (c) a heavy chain constant (C H ) region of an immunoglobulin epsilon heavy chain, and a pharmaceutically acceptable excipient. The scFv claimed in claim 67 does not, by definition, include the heavy chain and thus broadens the independent claims 66. Applicant may cancel the claim, amend the claim to place the claim(s) in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-15 AIA Claim s 66, 72, 153-155 and 163-164 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Coronella et al. (WO2018199176) . The reference discloses a binding agent that specifically binds to syndecan-1 (i.e. CD138), an extracellular domain of syndecan-1 or a portion thereof. In some embodiments a binding agent described herein binds specifically to a protein or polypeptide that comprises syndecan-1, an extracellular domain of syndecan-1 or a portion thereof. In certain embodiments, a binding agent binds specifically to one or more mammalian syndecan-1 polypeptides selected from a human syndecan-1, nonhuman primate syndecan-1 or a murine syndecan-1 ([0007]). The syndecan-1 binding agent is an antibody, or a binding fragment thereof and comprises a constant region of an IgE. The fragment is selected from a Fab, Fab', F(ab')2, Fv, Fd, single-chain Fv (scFv), disulfide-linked Fvs (sdFv), VL, VH, diabody ((VL-VH)2 or (VH-VL)2), triabody (trivalent), tetrabody (tetravalent), minibody ((scFV-CH3)2), scFv-Fc, (scFv)2-Fc, and binding fragments thereof. The syndecan-1 binding agent may be humanized or comprises at least one human constant region, or a portion thereof ([0017]-[0018]) and is comprised within a pharmaceutical composition ([0021]). Thus, in the broadest reasonable interpretation, the reference anticipates the instant claims 66, 72, 153-155 and 163-164 . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim s 67, 158, 159 and 162 are rejected under 35 U.S.C. 103 as being unpatentable over Coronella et al. (WO2018199176) in view of Tassone et al. (Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138 + multiple myeloma cells, Blood, 104, 3688-3696, 2004) . The claims add the limitation that the pharmaceutical composition comprising the heavy and light chains of an anti-CD138 antibody and a heavy chain constant (C H ) region of an immunoglobulin epsilon heavy chain, further comprises a chemotherapeutic which may be linked to the antibody. Also, for claim 67, the limitation is that the CD138- binding antibody is B-B4, BC/B-B4, B-B2, DL-101, 1D4, M115, 1.BB.210, 2Ql484, 5F7, 104-9, 281-2, or a Fab fragment thereof. The teachings of Coronella et al. were presented supra and they were silent about further chemotherapeutic in combination with the antibody or the exact antibodies mentioned in the instant claim 67. Tassone et al. teaches maytansinoid DM1 (N 2’ -deacetyl-N 2’ -(3-mercapto-1-oxopropyl)-maytansine), a potent antimicrotubule agent, covalently linked to the murine monoclonal antibody (mAb) B-B4 targeting syndecan-1 (CD138). These teachings suggest that B-B4–DM1 can overcome multiple myeloma (MM) cell growth, survival, and drug resistance within the BM milieu. B-B4–DM1 therefore represents a new generation of immunoconjugates with activity in both in vitro and in vivo preclinical models of MM, providing a preclinical rationale for clinical trials of B-B4–DM1 to improve patient outcome in MM (conclusion). It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have used the binding moieties of known in the art (B-B4, BC/B-B4, B-B2, DL-101, 1D4, M115, 1.BB.210, 2Q1484, 5F7, 104-9, 281-2) in the IgE antibodies of Coronella et al. with a reasonable expectation of success. This is because the binding moieties were known and a skilled artisan, desiring to obtain a CD138 binding IgE would have applied known and tested techniques existent in the art. Also, it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to attach chemotherapeutics to the IgE antibodies of Coronella et al. with a reasonable expectation of success, since the art was aware of CD138 antibodies bound to chemotherapeutics and this approach yielded reagents that can be used to specific targeting of chemotherapeutic drugs . 07-21-aia AIA Claim s 66, 67 and 148-155 are rejected under 35 U.S.C. 103 as being unpatentable over Pellizzari et al. (Trends in Mol. Med., 26, 615-626, 2020- cited by Applicant), in view of Chaudhary P.M. (WO2020150702) . The claims are drawn to a pharmaceutical composition comprising an antibody or antigen-binding fragment comprising: (a) a heavy chain variable (V H ) region of a CD138-binding antibody; (b) a light chain variable (V L ) region of the CD138-binding antibody; and (c) a heavy chain constant (C H ) region of an immunoglobulin epsilon heavy chain, and a pharmaceutically acceptable excipient. The V H region comprises SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 which, in turn, are comprised in SEQ ID NO: 7. The V L region comprises SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 which, in turn, are comprised in SEQ ID NO: 8. The C H region comprises SEQ ID NO: 9. The light chain constant (C L ) region of the antibody comprises an immunoglobulin kappa or lambda constant chain. Pellizzari et al. disclosed that IgE possess a very high affinity for cognate Fc receptors expressed by tumor-associated macrophages (TAMs) and reviewed studies that indicate control of cancer growth by tumor antigen-specific IgE that recruit and re-educate TAMs towards activated profiles. The clinical development harnessing the antitumor potential of recombinant IgE antibodies in cancer patients is also discussed (abstract). A mouse/human chimeric antibody (MOv18 IgE) specific for the tumor associated antigen folate receptor alpha (FRα) has been translated to a first-in-class, first-in man trial for the treatment of solid tumors (NCT02546921).TAMs represent an attractive target because they express both classes of cell surface IgE Fc receptor (Figs. 1-3). IgE engagement and Fc receptor cross-linking on TAMs could reactivate these cells against cancer. Antitumor IgE can prime human macrophages of different polarization states to elicit effector function responses and restrict tumor cell growth. Importantly, emerging evidence also supports a more prominent role for IgE than for IgG in re-educating M2 macrophages towards activated states, to feature higher expression of M1 macrophage markers such as CD80 and TNFα. These observations suggest that delivery of a tumor-specific IgE may alter the cellular and immunological dynamics in the TME, ultimately leading to tumor regression. Further dissection of the molecular interactions between macrophages and IgE in cancer may provide a promising avenue for the development of a new therapeutic strategy for solid tumors. The observations strengthen the case for the therapeutic potential of antitumor IgE, which seems able not only to mediate killing of cancer cells by ADCC, but also to play a role in re-education of TAMs from an anti-inflammatory profile to an M1-like phenotype (conclusion). Thus, the reference disclosed the proof of concept of targeted tumor antigen directed IgE. The reference does not teach the IgE binding molecules harboring CD138 binding CDRs. However, the CD138 antibody binding sequences were known in the art (see for instance Tassone et al. -cited supra ) or Chaudhary P.M. Chaudhary P.M. discloses antibody sequences that bind CD138 identical to SEQ ID NOs: 7 and 8 of the instant Application, comprised in the scFv of SEQ ID NO: 6411, and also disclosed the IgE sequence of the instant SEQ ID NO: 9. It would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have used known in the art V H and V L sequences of anti-CD138 antibody and construct an IgE antibody with a reasonable expectation of success. This is because Pellizzari et al. underscored the feasibility of the tumor specific IgE antibody as well as their superior qualities in specifically targeting cancer cells and triggering their demise . Allowable Subject Matter 12-151-08 AIA 07-43 12-51-08 Claim s 156 and 157 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion No calims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. 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ELLY-GERALD STOICA Primary Examiner Art Unit 1647 /Elly-Gerald Stoica/Primary Examiner, Art Unit 1647 Application/Control Number: 18/043,554 Page 2 Art Unit: 1647 Application/Control Number: 18/043,554 Page 3 Art Unit: 1647 Application/Control Number: 18/043,554 Page 4 Art Unit: 1647 Application/Control Number: 18/043,554 Page 5 Art Unit: 1647 Application/Control Number: 18/043,554 Page 6 Art Unit: 1647 Application/Control Number: 18/043,554 Page 7 Art Unit: 1647 Application/Control Number: 18/043,554 Page 8 Art Unit: 1647 Application/Control Number: 18/043,554 Page 9 Art Unit: 1647
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