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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-20 are all the original claims filed 11/3/2023. Claims 1-20 are the pending claims.
Priority
2. USAN 18/501,782, filed 11/03/2023, is a Continuation of 18/147,951, filed 12/29/2022, now abandoned, 18/147,951 is a Continuation of 16/649,617, filed 03/20/2020, now U.S. Patent # 11555072, 16/649,617 is a National Stage entry of PCT/US2018/052253, International Filing Date: 09/21/2018, PCT/US2018 /052253 Claims Priority from Provisional Application 62/562,374, filed 09/23/2017,
PCT/US2018/052253 Claims Priority from Provisional Application 62/562,373, filed 09/23/2017.
Information Disclosure Statement
3. As of 7/1/2026, a total of two (2) IDS are filed: 6/7/2024 and 10/28/2024. The corresponding initialed and dated 1449 form is considered and of record.
Objections
Specification
4. The disclosure is objected to because of the following informalities:
a) The use of the term, e.g., Uniprot, GenBank, EMBL, FlowJo, FACS, tykerb, luminol, Quil A, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
b) Amend the specification to teach “Quil-A” for proper spelling.
Appropriate correction is required.
Claim Objections
5. Claims 1 and 11 are objected to because of the following informalities:
a) Amend claim 1 to replace (a) and (b) with (i) and (ii), respectively.
b) Amend claim 11 to insert (i) and (ii), respectively, before each of “a heavy chain…” and “a light chain…”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Written Description
6. Claims 1-20 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 interpretation
Method claims 1-10 are drawn to generic configured structure (“Ig-related composition”) imbued with the functional properties of 1) treating any A33+ cancer, 2) increasing tumor sensitivity to radiation therapy, 3) binding A33 antigen, and 4) binding a DOTA hapten, in vivo, where the structure of the VH CDR1-3 (a) and VL CRD1-3 (b) are not defined by the antigen to which they bind, e.g., A33 and/or DOTA hapten.
Method claims 11-20 are drawn to generic configured structure imbued with the functional properties of 1) treating any A33+ cancer, 2) increasing tumor sensitivity to radiation therapy, 3) binding an A33 antigen, and 4) binding any DOTA hapten, in vivo, where the structure of the VH and VL are not defined by the antigen to which they bind, e.g., A33 and/or DOTA hapten.
Method claims 1-20 comprise a C825 binding fragment within the Ig-related composition.
Method claims 1-20 are drawn to three (3) administering steps in the diagnosed subject: Ig-related composition followed by a radiolabeled DOTA hapten, where a clearing reagent is administered prior to the Ig-related composition.
Method claims 1-20 are drawn to the Ig-related composition comprising an IgG1 constant region comprising mutations and a Fab, F(ab')2 Fab', scF, or Fv.
“configured”: the specification provides no definition for the term. The term is not defined by structure in order to ascertain how the property of tumor localization is conferred.
“Ig-related composition”: the specification makes general and specific disclosures for monospecific and bispecific antibodies throughout. Figure 1A exemplifies a bispecific structure for an anti-A33 x anti-CD3 antibody.
“binds… to a DOTA hapten” and the composition comprises a VH and VL”: the DOTA hapten binding aspect of the Ig-related composition is not limited in the claim set to being a VH, VL, CDRs or fragments thereof (i.e., antibody-related) but for claims 6-7 and 16-17 (C825 antibody). As noted above, the sequences denoted in claims 1 and 11 are not defined by the antigen to which they bind. The specification teaches a working example of the 2D12.5 (and C825) antibodies designed to capture and hold DOTA complexes, but any structure that binds a DOTA hapten known and yet to be discovered is encompassed by the claim scope.
“clearing agent”: the specification defines the reagent at
[0083] As used herein, a “clearing agent” is an agent that binds to excess bispecific antibody that is present in the blood compartment of a subject to facilitate rapid clearance via kidneys. The use of the clearing agent prior to hapten administration (e.g., DOTA) facilitates better tumor-to-background ratios in pretargeted radioimmunotherapy (PRIT) systems. Examples of clearing agents include 500 kD-dextran-DOTA-Bn(Y) (Orcutt et al., Mol Cancer Ther. 11(6): 1365-1372 (2012)), 500 kD aminodextran-DOTA conjugate, antibodies against the pretargeting antibody, etc.
The POSA could reasonably conclude that the clearing agent in the instant method is for the Ig-related complex and not the radiolabeled-DOTA hapten.
Scope of the Invention
The interpretation encompasses a method using a genus of therapeutic, structurally undefined Ig-related compositions beyond those taught in the specification for treating a subject diagnosed with/having a A33+ cancer. Because applicant seeks patent protection for all such methods, the genus must be adequately described. A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The purpose of the written description requirement is to “ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Summary of species disclosed in the specification
Anti-A33
The specification fully discloses a humanized anti-A33 antibody clone comprising the VH CDRs of instant claims 1 and 11. See Figure 14 where the VHCDR1 of mA33-VH is humanized by replacement of A with T (claimed as SEQ ID NO: 37):
PNG
media_image1.png
406
1026
media_image1.png
Greyscale
The specification fully discloses a humanized anti-A33 antibody clone comprising the VL CDRs of instant claims 1 and 11.
Anti-DOTA hapten
The specification fully discloses art-known examples for the anti-DOTA binding aspect of instant claims 1 and 11. C825 and 2D 12.5 are disclosed in Example 7 as being comprised on the same anti-huA33 x anti-C825 antibody where the anti-DOTA-Bn single chain Fv fragment (ScFv) based on an affinity matured 2D 12.5 antibody is linked to the carboxyl end of a humanized A33 light chain.
Anti-tumor properties of the bispecific anti-A33 x anti-DOTA hapten antibodies
Example 7: Use of huA33-C825 Antibodies of the Present Technology in Pretargeted Radioimmunotherapy at [0344-0358] for SW1222-tumor (colorectal cancer) bearing mice.
Example 8: In Vivo Therapeutic Effects of huA33-C825 Antibodies of the Present Technology [0359-0365] for SW1222-tumor (colorectal cancer) bearing mice.
Example 9: Ex Vivo Biodistribution Studies with the huA33-DOTA Bispecific Antibodies of the Present Technology [0366-0371] for SW1222-tumor (colorectal cancer) bearing mice.
Are the disclosed species representative of the claimed genus?
It is asserted that the disclosed species are not representative of the claimed genus because the claims encompass CDR sequences that are not defined by the antigen to which they bind, the genus of anti-DOTA hapten antibodies, the configured Ig-related composition that does not identify the structures responsible for 1) treating any A33+ cancer, 2) increasing any tumor sensitivity to radiation therapy, and 3) targeted binding for the A33 vs the DOTA hapten with specifically defined binding aspects.
The specification does not provide a common structure sufficient to visualize the genus
Applicant has not provided a common structure sufficient to visualize the genus of all possible configured Ig-related compositions correlated with a structure that imparts the function of 1) treating any A33+ cancer and 2) increasing any tumor sensitivity to radiation therapy.
While the prior art contains disclosure as to the structural features of anti-A33 antibodies and anti-DOTA hapten antibodies, it is unclear what structural features these antibodies need to share in order to maintain binding, therapeutic treatment and increased tumor sensitivity to radiation therapy. Even in 2021, therapeutic antibodies are still not understood well enough to allow researchers to predict with certainty what modifications can be made to a primary antibody sequence such that binding is maintained. “[T]he major test of understanding is whether the changes associated with antibody maturation can be predicted with any reasonable accuracy, and whether there is sufficient information for developing therapeutic antibodies,” Vajda et al., “Progress toward improved understanding of antibody maturation,” Current Opinion in Structural Biology, 67 pp. 226-231 (2021 (IDS 6/7/2024)) at p. 226, col. 2, lines 20-24.
As recently as 2020, researches were still speculating as to how to reliably identify further putative binders from antibody sequence data, see, e.g., Marks et al., “How repertoire data are changing antibody science,” J. Biol. Chem. 295(29) 9823-9837 (2020 (IDS 6/7/2024)), acknowledging that “there is a vast amount of the antibody sequence space that remains unknown,” p. 9831, col. 2, para. 2.
Even though the protein sequence of A33 (and the chemical structures of a DOTA hapten) were known in the art, this would not have translated into knowledge of the genus of antibodies that could possibly engage them. Computational and machine learning approaches for sequence-based prediction of paratope-epitope interactions are accumulating, but “it remains unclear whether antibody-antigen binding is predictable” (Akbar et al., Cell Reports 34, 108856, Mar. 16, 2021 at p. 2, col. 2, para. 2 (IDS 6/7/2024)). The current state of the art continues to work toward finding an effective and efficient prediction tool for reliably assigning antibody structure based on known target epitopes. See e.g., Lo et al., “Conformational epitope matching and prediction based on protein surface spiral features,” BMC Genomics volume 22, Article number: 116 (2021 (IDS 6/7/2024)) (disclosing new algorithms that calculate physicochemical properties, such as polarity, charge or the secondary structure of residues within the targeted protein sequences, and then applying quantitative matrix analyses or machine-learning algorithms to predict linear and conformational epitopes).
It is asserted that neither the specification nor the state of art at the time of filing disclosed structural features common to the members of the genus of configured Ig-related compositions for treating any A33+ cancer or increasing radiation-sensitivity of a tumor in a A33+ cancer subject for reliably assigning different antibody structures based on the limited disclosure in the specification. The absence of sufficient data supports the premise that the inventors did not possess the full scope of the claimed invention.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 –
(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.
7. Claim(s) 1-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheal et al (J Nucl Med 2017 Nov;58(11):1735-1742. doi: 10.2967/jnumed.117.193250. Epub 2017 Jul 13) (PTO 892).
The interpretation of the claims from section 6 is incorporated by reference.
Claims 1-20 are prima facie anticipated by Cheal.
AS regards claims 1-7, 9-17 and 19-20 Cheal teaches a 3-step pre-targeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)–targeting bispecific antibody and a small-molecule radioactive hapten, a complex of 177Lu and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclo dodecane tetra-acetic acid (177Lu-DOTA-Bn), that leads to high TIs for radiosensitive tissues such as blood and kidney. Fig 1B shows the 3-step anti-GPA33 DOTA-PRIT protocol comprising the administration of an “Ig-related composition” comprising GPA33, a bispecific antibody comprising anti-huA33 x C825 (anti-DOTA), followed by hapten/dextran clearing agent, and M-DOTA complex formation with GPA33.
Cheal teaches the model defines the use of GPA33-postive human CRC cell line SW1222 in testing the anti-GPA33 DOTA-PRIT protocol.
Cheal teaches the primary features include that the modular bispecific antibody format (IgG-scFv) offers multivalent and simultaneous antibody binding of 2 distinct antigens: a tumor antigen and the pM affinity anti-DOTA hapten anti body fragment C825 that recognizes small radioactive yttrium or lutetium-chelate complexes of DOTA-Bn; and the use of radio-haptens (e.g., 177Lu-DOTA-Bn) with almost exclusive renal clearance and with negligible retention in normal tissue.
Cheal teaches determined that the addition of cycle 3 contributed 10% of the total absorbed dose by tumor, which was essential for histologic cure of the 9 of 9 tumors examined after treatment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
8. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11555072 in view of Cheal et al (J Nucl Med 2017 Nov;58(11):1735-1742. doi: 10.2967/jnumed.117.193250. Epub 2017 Jul 13). AS to the reference patent, the instant application is a CON thereof so the ref patent is not afforded safe harbour under 35 USC 121. Although the claims at issue are not identical, they are not patentably distinct from each other because the ref patent claims share 100% identity with the VHCDR1-3 of element (a) claim 1 and VLCDR1-3 of element (b) of claim 1 for the bispecific antibody GPA33 of the instant claims 1-10 and Cheal. The ref bispecific antibody includes the ability to bind a small molecule DOTA hapten denoting the presence of an anti-DOTA hapten binding aspect. The ref claims teach identical IgG1 with substitutions. The ref claims teach identical antibody fragments.
1. An anti-A33 antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein: (a) the V.sub.H comprises a V.sub.H-CDR1 sequence of FTFSTYDMS (SEQ ID NO: 37), a V.sub.H-CDR2 sequence of TISSGGSYTYYLDSVKG (SEQ ID NO: 38), and a V.sub.H-CDR3 sequence of TTVVPFAY (SEQ ID NO: 39); and (b) the V.sub.L comprises a V.sub.L-CDR1 sequence, a V.sub.L-CDR2 sequence, and a V.sub.L-CDR3 sequence selected from the group consisting of: KASQNVRTVVA (SEQ ID NO: 40), LASNRHT (SEQ ID NO: 41), and QYWSYPLT (SEQ ID NO: 42); KASQNVRTVVA (SEQ ID NO: 40), LASDRHT (SEQ ID NO: 43), and QYWSYPLT (SEQ ID NO: 42); KASQNVRTLVA (SEQ ID NO: 44), LASNRHT (SEQ ID NO: 41), and QHWSYPLT (SEQ ID NO: 45); and KASQNVRTLVA (SEQ ID NO: 44), LASNRHT (SEQ ID NO: 41), and QYWSYPLT (SEQ ID NO: 42), optionally wherein the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, or a bispecific antibody, or the antigen binding fragment is selected from the group consisting of Fab, F(ab′).sub.2, Fab′, scF.sub.v, and F.sub.v and optionally wherein the bispecific antibody binds to T cells, B-cells, myeloid cells, plasma cells, mast-cells, CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma/delta, NKp46, KIR, or a small molecule DOTA hapten.
2. The antibody or antigen binding fragment of claim 1, further comprising a Fe domain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgM, IgD, and IgE, optionally wherein IgG1 comprises one or more amino acid substitutions selected from the group consisting of N297A and K322A; or IgG4 comprises a S228P mutation, or the antibody lacks α-1,6-fucose modifications.
3. A composition comprising the antibody or antigen binding fragment of claim 1 and a pharmaceutically-acceptable carrier, wherein the antibody or antigen binding fragment is optionally conjugated to an agent selected from the group consisting of dyes, chromagens, contrast agents, drugs, metals, liposomes, nanoparticles, RNA, and DNA, or any combination thereof, optionally wherein the drugs comprise one or more of toxins, cytokines, enzymes, enzyme inhibitors, hormones, hormone antagonists, growth factors, and radionuclides, optionally wherein the radionuclides comprise isotopes.
4. An anti-A33 antibody or antigen binding fragment thereof comprising a heavy chain immunoglobulin variable domain (VH) amino acid sequence present in SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 15, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35, SEQ ID NO: 58, or SEQ ID NO: 62, and a light chain immunoglobulin variable domain (VL) amino acid sequence present in SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 17, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 36, SEQ ID NO: 60, or SEQ ID NO: 63, optionally wherein the antibody is a chimeric antibody, a humanized antibody, or a bispecific antibody and optionally wherein the bispecific antibody binds to T cells, B-cells, myeloid cells, plasma cells, mast-cells, CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma/delta, NKp46, KIR, or a small molecule DOTA hapten.
5. A recombinant nucleic acid sequence encoding the antibody or antigen binding fragment of claim 4 selected from the group consisting of: SEQ ID NOs: 7, 8, 11, 12, 16, 18, 20, 22, 59 and 61.
6. A host cell or vector comprising the recombinant nucleic acid sequence of claim 5.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref patent claims share 100% identity with the VH of element (a) claim 11 and VL of element (b) of claim 11 for the bispecific antibody GPA33 of the instant claims 11-20 and Cheal. The ref bispecific antibody includes the ability to bind a small molecule DOTA hapten denoting the presence of an anti-DOTA hapten binding aspect. The ref claims teach identical IgG1 with substitutions. The ref claims teach identical antibody fragments.
7. An anti-A33 antibody comprising a HC amino acid sequence and a LC amino acid sequence selected from the group consisting of: SEQ ID NO: 5 and SEQ ID NO: 9; SEQ ID NO: 5 and SEQ ID NO: 10; SEQ ID NO: 6 and SEQ ID NO: 9; SEQ ID NO: 6 and SEQ ID NO: 10; SEQ ID NO: 15 and SEQ ID NO: 17; SEQ ID NO: 19 and SEQ ID NO: 21; SEQ ID NO: 23 and SEQ ID NO: 24; SEQ ID NO: 25 and SEQ ID NO: 26; SEQ ID NO: 27 and SEQ ID NO: 28; SEQ ID NO: 29 and SEQ ID NO: 30; SEQ ID NO: 31 and SEQ ID NO: 32; SEQ ID NO: 33 and SEQ ID NO: 34; SEQ ID NO: 35 and SEQ ID NO: 36; SEQ ID NO: 58 and SEQ ID NO: 60; and SEQ ID NO: 62 and SEQ ID NO: 63, respectively, optionally wherein the antibody is a chimeric antibody, a humanized antibody, or a bispecific antibody, and optionally wherein the bispecific antibody binds to T cells, B-cells, myeloid cells, plasma cells, mast-cells, CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma/delta, NKp46, KIR, or a small molecule DOTA hapten.
8. The antibody of claim 7, wherein the antibody comprises an IgG1 constant region comprising one or more amino acid substitutions selected from the group consisting of N297A and K322A, or wherein the antibody comprises an IgG4 constant region comprising a S228P mutation or wherein the antibody lacks α-1,6-fucose modifications.
9. The bispecific anti-A33 antibody of claim 7, wherein the bispecific antibody binds to a radiolabeled DOTA hapten.
10. A composition comprising the antibody of claim 7 and a pharmaceutically-acceptable carrier, wherein the antibody is optionally conjugated to an agent selected from the group consisting of dyes, chromagens, contrast agents, drugs, metals, liposomes, nanoparticles, RNA, and DNA, or any combination thereof, optionally wherein the drugs comprise one or more of toxins, cytokines, enzymes, enzyme inhibitors, hormones, hormone antagonists, growth factors, and radionuclides, optionally wherein the radionuclides comprise isotopes.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ref patent claims are drawn to a treating/ increasing tumor sensitivity to radiation for a A33 cancer using the A33 antibody of the product claims including a bispecific component share 100% identity with the VHCDR1-3/VH of element (a) claims 1/11 and VL/VLCDR1-3 of element (b) of claims 1/11 for the bispecific antibody GPA33 comprising an anti-DOTA hapten binding arm and radiolabeled DOTA hapten to the subject such as claimed and by Cheal.
11. A method for treating an A33 expressing cancer in a subject in need thereof, comprising administering to the subject an effective amount of the antibody of claim 7, wherein the antibody specifically binds to and neutralizes A33 activity, optionally wherein the A33 expressing cancer is colorectal cancer, Pseudomyxoma peritonei, appendiceal cancer, pancreatic cancer, or gastric cancer.
12. The method of 11, wherein the antibody is administered to the subject separately, sequentially or simultaneously with an additional therapeutic agent.
13. The method of claim 12, wherein the additional therapeutic agent is one or more of alkylating agents, platinum agents, taxanes, vinca agents, anti-estrogen drugs, aromatase inhibitors, ovarian suppression agents, VEGF/VEGFR inhibitors, EGF/EGFR inhibitors, PARP inhibitors, cytostatic alkaloids, cytotoxic antibiotics, antimetabolites, endocrine/hormonal agents, and bisphosphonate therapy agents.
14. The method of claim 11, wherein the A33 expressing cancer is colorectal cancer with a MSI genotype or a MSS genotype, or wherein the colorectal cancer is associated with a KRAS G12D mutation or a p53 mutation.
15. A method for detecting a tumor in a subject in vivo comprising (a) administering to the subject an effective amount of an antibody of claim 9, wherein the antibody is labeled with a radioisotope; and (b) detecting the presence of a tumor expressing A33 in the subject by detecting radioactive levels emitted by the antibody that are higher than a reference value, optionally wherein the radioactive levels emitted by the antibody are detected using positron emission tomography or single photon emission computed tomography, or the subject is diagnosed with or is suspected of having cancer.
16. The method of claim 15, further comprising administering to the subject an effective amount of an immunoconjugate comprising the antibody of claim 9 conjugated to a radionuclide.
17. The method of claim 16, wherein the radionuclide is an alpha particle-emitting isotope, a beta particle-emitting isotope, an Auger-emitter, or any combination thereof, optionally wherein the beta particle-emitting isotope is selected from the group consisting of .sup.86Y, .sup.90Y, .sup.89Sr, .sup.165Dy, .sup.186Re, .sup.88Re, .sup.177Lu, and .sup.67Cu.
18. A method for detecting solid tumors in a subject in need thereof comprising (a) administering to the subject an effective amount of a complex comprising a radiolabeled DOTA hapten and the bispecific antibody of claim 9; and (b) detecting the presence of solid tumors expressing A33 in the subject by detecting radioactive levels emitted by the complex that are higher than a reference value.
19. A method for selecting a subject for pretargeted radioimmunotherapy comprising (a) administering to the subject an effective amount of a complex comprising a radiolabeled DOTA hapten and the bispecific antibody of claim 9; (b) detecting the presence of solid tumors expressing A33 in the subject by detecting radioactive levels emitted by the complex; and (c) selecting the subject for pretargeted radioimmunotherapy when the radioactive levels emitted by the complex are higher than a reference value.
20. A method for treating A33 expressing cancer in a subject in need thereof or increasing tumor sensitivity to radiation therapy in a subject with A33 expressing cancer comprising administering to the subject an effective amount of a complex comprising a radiolabeled DOTA hapten and the bispecific antibody of claim 9.
21. A method for treating A33 expressing cancer in a subject in need thereof or increasing tumor sensitivity to radiation therapy in a subject with A33 expressing cancer comprising (a) administering an effective amount of the bispecific antibody of claim 9; and (b) administering an effective amount of the radiolabeled-DOTA hapten to the subject.
Cheal teaches a 3-step pre-targeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)–targeting bispecific antibody and a small-molecule radioactive hapten, a complex of 177Lu and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclo dodecane tetra-acetic acid (177Lu-DOTA-Bn), that leads to high TIs for radiosensitive tissues such as blood and kidney. Fig 1B shows the 3-step anti-GPA33 DOTA-PRIT protocol comprising the administration of an “Ig-related composition” comprising GPA33, a bispecific antibody comprising anti-huA33 x C825 (anti-DOTA), followed by hapten/dextran clearing agent, and M-DOTA complex formation with GPA33.
Cheal teaches the model defines the use of GPA33-postive human CRC cell line SW1222 in testing the anti-GPA33 DOTA-PRIT protocol.
Cheal teaches the primary features include that the modular bispecific antibody format (IgG-scFv) offers multivalent and simultaneous antibody binding of 2 distinct antigens: a tumor antigen and the pM affinity anti-DOTA hapten anti body fragment C825 that recognizes small radioactive yttrium or lutetium-chelate complexes of DOTA-Bn; and the use of radio-haptens (e.g., 177Lu-DOTA-Bn) with almost exclusive renal clearance and with negligible retention in normal tissue.
Cheal teaches determined that the addition of cycle 3 contributed 10% of the total absorbed dose by tumor, which was essential for histologic cure of the 9 of 9 tumors examined after treatment.
Conclusion
9. No claims are allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
Prosecution Insights