T Cell Sciences Inc. is announcing today that the U.S. Patent andTrademark Office has just awarded the company Patent No.5,212,071, dated May 18, covering "Nucleic Acids Encoding aHuman C3B/C4B Receptor (CR1)."
The drug's therapeutic purpose is to spare victims of manydisorders from damage to healthy tissue inflicted by an over-active complement cascade. Like warfare's "friendly fire,"which inadvertently decimates troops on one's own side,molecules of the complement system -- advance patrols sentahead to mop up invading pathogens while the immune systemis mobilizing its antibody and lymphocyte defenses --frequently don't know when to stop (see BioWorld, Dec. 15,1992).
Lysing of healthy cells by excessive complement activationthreatens a patient population of nearly 2 million in the U.S.,according to T Cell Sciences statistics.
The Cambridge, Mass., company's just-patented recombinant,soluble complement blocking receptor, sCR1, "is the firstcomplement inhibiting factor to be tested in humans," said AlanTuck, T Cell's president and chief executive officer. "Currently,there are no approved drug therapies that directly addressinappropriate complement-mediated tissue damage," he added.
The sCR1 complement curbing compound has been in Phase Iclinical trials since mid-December, to measure toxicity anddosing. This initial study is a placebo-controlled, double-blindtrial to protect burn victims from the collateral complement-inflicted lung damage of ARDS (adult respiratory diseasesyndrome). It is being conducted by T Cell's R&D partner,SmithKline Beecham, at burn centers in the U.S., and willeventually enroll up to 50 patients. "We anticipate the trial willcontinue through 1993," said T Cell's manager of developmentand communications, B. G Susan Primrose.
Seven inventors share title to the patent, issued jointly to JohnsHopkins University in Baltimore, Brigham and Women'sHospital in Boston and T Cell Sciences, the exclusive licensee.
The patent states that the invention it covers "relates to theC3b/C4b receptor (CR1) gene and its encoded protein." Its 64claims list nucleic acid sequences and recombinantly producedmolecules, along with an inventory of related vectors, hostorganisms and production methods.
Claim 20 cites "an isolated nucleic acid encoding a soluble CR1molecule substantially lacking a transmembrane region, whichCR1 molecule has a complement regulatory activity." This claimprotects the solublization of the receptor molecule, whichconfers complement-blocking bioactivity on the compound.
Tuck said the patent also "covers a number of other moleculeswe are evaluating as second-generation compounds." These,Primrose told BioWorld, involve truncated sequences toinactivate specific parts of the complement pathway, ratherthan the entire cascade. She said that T Cell Sciences is to herknowledge the only player playing the recombinant receptorcard.
CORPSES CLARIFY COMPLEMENT ROLE
The first scientific experiment to hint at what complement is allabout appeared in Lancet in 1894 (Vol. 1, Page 1,236), titled"The Action of Rattlesnake Venom Upon the Bactericidal Powerof the Blood Serum."
Its author, U.S. Army surgeon Charles E. Ewing, attempted toanswer the question: Why does a corpse killed by a rattlesnakebite decompose so much faster than one laid low by a bullet?In controlled trials on rabbits, inoculated or not with venom,Ewing found that the venomized "blood at the time of death @had lost all power of resisting the invasion and multiplicationof @ the bacteria of putrefaction, which are normally present inthe intestine, develop with astounding rapidity, and evenbefore the animal is cold produce this wonderful rapiddecomposition."
Later scientists determined that venom deactivates the serum-complement factors.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.