Pharmaceutical compositions comprising antibody-urease conjugates and substantially free of unconjugated urease are disclosed. These compositions are prepared by a method that does not require chromatographic purification. These pharmaceutical compositions have utility in the treatment of cancer by antibody-directed enzyme prodrug therapy wherein the urease converts endogenous urea into ammonia in situ to induce cytotoxicity.

The present invention concerns improved methods and compositions for preparing SN-38 conjugates of proteins or peptides, preferably immunoconjugates of antibodies or antigen-binding antibody fragments. More preferably, the SN-38 is attached to the antibody or antibody fragment using a CL2A linker, with 1-12, more preferably 6-8, alternatively 1-5 SN-38 moieties per antibody or antibody fragment. Most preferably, the immunoconjugate is prepared in large scale batches, with various modifications to the reaction scheme disclosed herein to optimize yield and recovery in large scale. Other embodiments concern optimized dosages and/or schedules of administration of immunoconjugate to maximize efficacy for disease treatment and minimize side effects of administration.

Provided is an anti-CEA antibody comprising a heavy chain variable region and a light chain variable region, a drug conjugate thereof, and a composition containing the anti-CEA antibody or the drug conjugate thereof, and an application thereof as a drug.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

An anti-CEA antibody-exatecan analog conjugate and a pharmaceutical use thereof. Specifically, the anti-CEA antibody-exatecan analog conjugate is as shown in general formula (Pc-L-Y-D), wherein Pc is an anti-CEA antibody or an antigen-binding fragment thereof; L is a linker unit; Y is selected from —O—(CR.sup.aR.sup.b).sub.m—CR.sup.1R.sup.2—C(O)—, —O—CR.sup.1R.sup.2—(CR.sup.aR.sup.b).sub.m—, —O—CR.sup.1R.sup.2—, —NH—(CR.sup.aR.sup.b).sub.m—CR.sup.1R.sup.2—C(O)—, and —S—(CR.sup.aR.sup.b).sub.m—CR.sup.1R.sup.2—C(O); and n is a decimal or integer from 1 to 10.

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The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more 8-amido-2-aminobenzazepine derivatives. The invention also provides 8-amido-2-aminobenzazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

The present invention concerns antibody-conjugates comprising an anti-CEACAM5-antibody for use for treating cancer in combination with folinic acid, 5-fluoro-uracil and irinotecan (FOLFIRI). The invention further relates to pharmaceutical compositions and kit-of-parts comprising an anti-CEACAM5-antibody in combination with folinic acid, 5-fluoro-uracil and irinotecan (FOLFIRI) for use for treating cancer.

The present invention concerns antibody-conjugates comprising an anti-CEACAM5-antibody for use for treating cancer in combination with folinic acid, 5-fluoro-uracil and irinotecan (FOLFIRI). The invention further relates to pharmaceutical compositions and kit-of-parts comprising an anti-CEACAM5-antibody in combination with folinic acid, 5-fluoro-uracil and irinotecan (FOLFIRI) for use for treating cancer.

The invention provides immunoconjugates of Formula (I) comprising an antibody linked by conjugation to one or more aminoquinoline derivatives. The invention also provides aminoquinoline derivative intermediate compositions of Formula (III) comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

[Object] It is an object of the present invention to provide a conjugate of a biotin-modified dimer and a phthalocyanine dye, which is used in photoimmunotherapy.

[Means for Solution] A compound represented by the following formula (1) or a salt thereof:

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wherein X represents a substituent having a hydrophilic group, a cationic group or an amino group at the terminus thereof, or —OH, and other groups have the meanings as defined in the description.