PGtent Report This section provides information on worldwide patents relevant to vaccine design and production. The Patent Report gives the following information: title of patent, patentee, patent number, publication and summary of the patent. A number of patents in this report are reproduced from 'Biotechnology Abstracts' with permission of Derwent Publications Ltd.

Escherichia coli neurotoxin detoxified with glutaraldehyde; terminating reaction before 90% inactiviation; pig edema disease vaccine

SK + F-RIT Eur. 88-302; 14 September 1983

A process for the preparation of Escherichia coli neurotoxin detoxified by reaction with glutaraldehydes, comprises reaction under gentle conditions and terminating reaction before 90% of the neurotoxin has been inactivated. This produces a detoxified neurotoxin which still has im- munogenic activity. The detoxified neurotoxin is preferably absorbed on an aluminum phosphate or hydroxide adjuvant. The toxin is used in the preparation of vaccines against pig edema disease (intestinal edema or enterotoxemia). The vaccines are not toxic but strongly immunogenic and are used to vaccinate piglets about 1 week old. 023-84

Immunogenic non-covalent polysaccharide-protein capsular complexes; Haemophilus influenza type b and Neiseria meningitidis group b; vaccine preparation

SK + F-RIT Eur 88-303; 14 September 1983

A process for the preparation ofimmunogenic non-covalent, polysaccharide-protein bacterial capsular complexes, free from lipopolysaccharides, from an aqueous suspension of bacteria. It comprises inactivating the bacteria by addition of a quaternary ammonium salt (preferably centrimonium bromide), immediately recovering the insoluble fraction, which is taken up in a 0.2-2N non-toxic alkali metal or alkaline earth metal salt solution. Contaminants are pre- cipitated out by addition of 25% aqueous ethanol, removing the quarternary ammonium salt by addition of a water- soluble benzoate, sulphocyanide or iodide and separating the ,precipitate to give an aqueous solution from which the complex is recovered. The complex is purified by ultra- filtration and lyophilization. Haemophilus influenzae type b and Neisseria meningitidis group b were used. The method is used for the preparation of vaccines against meningitis using effective doses of the above complexes. 024-84

Bacterial toxoid(s) formed irreversibly from toxin(s) Pseudo- monas aeruginosa exotoxin A and antiserum from J-5 Escherichia coli vaccine composition against general Gram positive bacteremia

Merck-USA Eur 89-283; 21 September 1983

Toxoids of formula (I) (where R is an ADP-ribosylating toxin radical and X is H or a group of formula (II) are new. The toxoids are formed irreversibly from the bacterial toxins and retain the antigenic and immunogenic properties of the parent toxins and so are useful as immunogens in vaccines against the specific diseases caused by the parent toxins. With Pseudomonas aeruginosa the toxoid may be combined with vaccines to bacterial endotoxins or antisera produced from

them to give a broader spectrum of protection against Gram- negative bacteremia than was previously possible. Preferably in (I) R is an exotoxin A from Pseudomonas aeruginosa, the heat-labile enterotoxin from Escherichia coli, the cholera enterotoxin from Vibrio cholerae or the diphtheria exotoxin from Corynebacterium diphtheriae. Toxoids are obtained by mixing_the toxin with 8-azido-adenosine or -adenine (photo- labile reage~nts) at 0°C in an inert atmosphere and the mixture is exposed to non-denaturing light. 025-84

NH

NHR HO

OH OH

( i ) (tt)

Prophylaxis of colienterotoxemia in fowl using Escherichia coli strains

Nisshin Jpn unexamined 8135-819; 12 August 1983

Prophylaxis of colienterotoxemia in fowl comprises in- oculating live or dead cells ofEscherichia coli NS-244 via the cloaca. The preventative agent may be a combination of living or dead cells ofE. coli NS-244 with dead cells ofE. coli O1 or 02, or O1-O2. The E. coli organisms are inactivated by ,/-irradiation, u.v. irradiation, or by treatment with formalde- hyde. The inoculation is performed using an infusion, by dropping, spraying, immersion or by painting. By use of this method, colibacillemia can be prevented without adverse reactions occurring. No resistant strains ofE. coli were found to occur. E. coli strain NS-244 (FERM-P 5757) has no pathogenicity to chicken. An adjuvant may be added to the preparation, and immune antigens or nonpathogenic antigens, may be added. The cells are dispersed in water, physiological saline, phosphate buffer or tissue culture solution before their administration. 026-84

Novel rabies virus strain and a process for its preparation: application to vaccine production

Brocades US 4,400,472; 23 August 1983

The new rabies virus strain was isolated b~ propagating the high egg passage (HEP) Flury vaccine in primary or secondary SPF chicken embryo fibroblasts. In view of the very rapid production of interferon and cellular mediated immunity, the application of the vaccines of the invention for the protection of recently exposed animals during outbreaks of rabies is now feasible, and the possibility of post-exposure' vaccine treatment of humans has been considerably improved. The new strain may be administered by different routes. Monolayers of primary or secondary SPF chicken embryo fibroblasts grown in stationary or roller bottles were infected with the rabies seed virus strain 675. After 1 h, unattached virus was removed and maintenance medium, consisting of basal medium Eagle (BME) supplemented with antibiotics and albumin, was added. After 4-8 days of incubation at 33"35~C, a pronounced cytopathic effect was seen. The medium was frozen and the cells were removed by centrifugation or membrane filtration. The supernatant or filtrate was used for vaccine production. 027-84

162 Vaccine, Vol. 2, June 1 9 8 4