Claims for Patent: 9,028,800

Summary for Patent: 9,028,800

Title:	Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules
Abstract:	The present application discloses compositions and methods of synthesis and use of .sup.18F or .sup.19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the .sup.18F or .sup.19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the .sup.18F or .sup.19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.
Inventor(s):	D\'Souza; Christopher A. (Pomona, NY), McBride; William J. (Boonton, NJ), Goldenberg; David M. (Mendham, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	14/273,163
Patent Claims:	1. A composition comprising an .sup.19F- or .sup.18F-labeled targeting molecule comprising a bifunctional chelating agent of the structure ##STR00026## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of --CH.sub.2--COOH --CH.sub.2--CH.sub.2--OH --CH(CH.sub.3)--COOH --CH(C.sub.6H.sub.5)--COOH ##STR00027## and R.sub.3 is selected from the group consisting of: ##STR00028## ##STR00029## wherein M selected from the group consisting of aluminum, gallium, indium, lutetium and thallium and X is .sup.19F or.sup.l8F, wherein n =1-9 and wherein R.dbd.F, CH.sub.2F, CHF.sub.2, CH.sub.3 or OCF.sub.3. 2. The composition of claim 1, wherein the targeting molecule is selected from the group consisting of a protein, a peptide, an antibody, a monoclonal antibody, a bispecific antibody, a multispecific antibody, an antibody fusion protein, an antigen-binding antibody fragment, an affibody and a targetable construct. 3. The composition of claim 2, wherein the antibody is selected from the group consisting of hR1 (anti-IGF-1R), hPAM4 (anti-pancreatic cancer mucin), hA20 (anti-CD20), hA19 (anti-CD 19), hIMMU31 (anti-AFP), hLL1 (anti-CD74), hLL2 (anti-CD22), hMu-9 (anti-CSAp), hL243 (anti-HLA-DR), hMN-14 (anti-CEACAM5), hMN-15 (anti-CEACAM6), hRS7 (anti-EGP-1) and hMN-3 (anti-CEACAM6). 4. The composition of claim 2, wherein the antibody is selected from the group consisting of Ab 124 (anti-CXCR4), Ab125 (anti-CXCR4), abciximab (anti -glycoprotein IIb/IIIa), alemtuzumab (anti-CD52), bevacizumab (anti-VEGF), cetuximab (anti-EGFR), gemtuzumab (anti-CD33), ibritumomab (anti-CD20), panitumumab (anti-EGFR), rituximab (anti-CD20), tositumomab (anti-CD20), trastuzumab (anti-ErbB2), abagovomab (anti-CA-125), adecatumumab (anti-EpCAM), atlizumab (anti-IL-6 receptor), benralizumab (anti-CD125), CC49 (anti-TAG-72), AB-PG1-XG1-026 (anti-PSMA), D2/B (anti-PSMA), tocilizumab (anti-IL-6 receptor), basiliximab (anti-CD25), daclizumab (anti-CD25), efalizumab (anti-CD11a), GA101 (anti-CD20), muromonab-CD3 (anti-CD3 receptor), natalizumab (anti-.alpha.4 integrin), omalizumab (anti-IgE), infliximab (anti-TNF-.alpha.), certolizumab pegol (anti-TNF-.alpha.), adalimumab (anti-TNF-.alpha.), and belimumab (anti-BLyS). 5. The composition of claim 2, wherein the antibody fragment is selected from the group consisting of F(ab').sub.2, Fab', F(ab).sub.2, Fab, scFv and VHH (single domain antibody). 6. The composition of claim 1, wherein the targeting molecule binds to a tumor-associated antigen (TAA). 7. The composition of claim 5, wherein the TAA is selected from the group consisting of carbonic anhydrase IX, CCL19, CCL21, CSAp, CD1, CD1a, CD2, CD3, CD4, CD5, CD8, CD11A, CD14, CD15, CD16, CD18, CD19, IGF-1R, CD20, CD21, CD22, CD23, CD25, CD29, CD30, CD32b, CD33, CD37, CD38, CD40, CD40L, CD45, CD46, CD52, CD54, CD55, CD59, CD64, CD66a-e, CD67, CD70, CD74, CD79a, CD80, CD83, CD95, CD126, CD133, CD138, CD147, CD154, CXCR4, CXCR7, CXCL12, HIF-1-.alpha., AFP, PSMA, CEACAM5, CEACAM-6, c-met, B7, ED-B of fibronectin, Factor H, FHL-1, Flt-3, folate receptor, GROB, HMGB-1, hypoxia inducible factor (HIF), insulin-like growth factor-1 (ILGF-1), IFN-65 , IFN-.alpha., IFN-.beta., IL-2, IL-4R, IL-6R, IL-13R, IL-15R, IL-17R, IL-18R, IL-6, IL-8, IL-12, IL-15, IL-17, IL-18, IL-25, IP-10, MAGE, mCRP, MCP-1, MIP-1A, MIP-1B, MIF, MUC1, MUC2, MUC3, MUC4, MUC5, NCA-95, NCA-90, Ia, EGP-1, EGP-2, HLA-DR, tenascin, Le(y), RANTES, T101, TAC, Tn antigen, Thomson-Friedenreich antigens, tumor necrosis antigens, TNF-.alpha., TRAIL receptor (R1 and R2), VEGFR, EGFR, P1GF, complement factors C3, C3a, C3b, C5a, and C5. 8. The composition of claim 1, wherein the targeting molecule is somatostatin, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), bombesin, methotrexate, growth hormone, RGD (arginine-glycine-aspartic acid) or folic acid. 9. The composition of claim 1, wherein M is aluminum. 10. The composition of claim 1, wherein multiple copies of the bifunctional chelating agent are attached to the targeting molecule. 11. The composition of claim 1, further comprising an aqueous medium. 12. The composition of claim 11, wherein the composition is at a pH of about 3.5 to 4.5. 13. The composition of claim 1, further comprising an organic solvent. 14. The composition of claim 13, wherein the organic solvent is selected from the group consisting of acetonitrile, ethanol, dimethylformamide, methanol, acetone, propanol, isopropanol, butanol, tent-butanol, tetrahydrofuran, dioxane and dimethylsulfoxide. 15. The composition of claim 11, further comprising ascorbic acid, potassium biphthalate, ethanol and trehalose.

Details for Patent 9,028,800

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2027-01-11
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2027-01-11
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-01-11
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-01-11
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2027-01-11