xviii New Patents

A method for enhancing the ability for humoral immune response in a mammal comprising: ex- posing lymphocytes histocompatible with the lymphocytes of said mammal to the presence of delta-immunoglobulin at a concentration higher than that at which said lymphocytes would have been exposed while in the lymph or bloodstream of said mammal; and introducing said lympho- cytes to the bloodstream or lymph of said mam- mal.

4937183

METHOD FOR THE PREPARATION OF ANTIBODY-

FRAGMENT CONJUGATES

cytes, macrophages) and cellular debris will form a supernatant while the remaining fragments containing aggregated tumor cells are deposited in a sediment layer. Preferably, the medium is an isotonic tissue culture medium and decantation is conducted at least twice; first in a serum- containing medium and then, secondly, in a serum-free medium. Fragments containing

. living tumor cells can be selected by fluorochromasia, that is, by contacting the sedimented layer with a fluorogenic substrate such that viable tumor cells take up and hydro- lyse the substrate, and then exhibit fluorescence. Cytotoxicity assay protocols employing tumor cell aggregates prepared by the present techni- ques are also disclosed.

4937188

Michiel Ultee, Vernon L Alvarez assigned to Cytogen Corporat ion

A novel method for preparing soluble antibody fragment compositions having superior charac- teristics for targeted delivery when administered in vivo are disclosed. The antibody fragment compositions are characterized by substantially the same immunospecificity as the unconjugated antibody and aqueous solubility such that they are suitable for in vivo administration. Therapeutic and diagnostic methods utilizing the antibody fragment compositions are also dis- closed.

4937187

M E T H O D S F O R S E P A R A T I N G M A L I G N A N T C E L L S F R O M

C L I N I C A L S P E C I M E N S

M Boris Rotman assigned to Brown University Research Foundat ion

Fragments of a biopsy sample on the order of about 50 to 5000 cells are preferred for establishing viable tumor cell cultures for pur- poses such as establishing cell lines, chem- otherapeutic assays and the like. Such fragments retain the three-dimensional cellular structure or organization of the original tumor and, there- fore, can be cultured more readily. To obtain such fragments suitable for culturing, the biopsy sample can be enzymatically digested in a pro- teolytic or nucleolytic enzyme, such as col- lagenase, or by mechanical dissociation, or both where necessary. The fragments can then be suspended in an aqueous medium so that non- aggregated cells (e.g., red blood cells, lympho-

E N Z Y M E A C T I V I T Y A M P L I F I C A T I O N M E T H O D F O R

I N C R E A S I N G A S S A Y S E N S I T I V I T Y

Roger W Giese, Marku Ehrat, Douglas J Cec- chini assigned to Northeastern University

Enzyme amplification is achieved by covalently bonding enzyme to a supporting material via a molecular chain which is a substrate for the en- zyme, then introducing a small amount of en- zyme in the free state to this system, causing release of a large amount of bound enzyme. In an alternative embodiment, complementary en- zymatically inactive fragments of an active en- zyme, which fragments can recombine to form active enzyme, are covalently attached to separate support materials by a molecular chain material which is a substrate for the active en- zyme, and these two fragment-support con- jugates are connected in series. Upon application of free enzyme or free complementary enzyme to one of these fragment-support conjugates, fol- lowed by application of the resulting product mixture to the second fragment-support con- jugate, a large amount of free enzyme is ul- timately produced. In a second alternative embodiment, two different active enzymes are each attached to separate supporting materials by different leashes, in which the leash for the first enzyme only is cleaved in the system by the second enzyme, and the leash for the second en- zyme only is cleaved in the system by the first en- zyme. These two materials are connected in series, and upon application of the second en- zyme to the first enzyme-support conjugate, fol- lowed by application of the released first enzyme to the second enzyme-support conjgate material, ultimately a large amount of released active