Patent Profile: Immunomedics Announces Patent for Dock-and-Lock Antibody Assemblies

    By Mark Chael --

On May 5th, Immunomedics, Inc. announced that its majority-owned subsidiary, IBC Pharmaceuticals, Inc., was granted U.S. Patent No. 7,527,787, entitled "Multivalent Immunoglobulin-based Bioreactive Assemblies."  Claim 1 from the patent reads:

1.  A hexameric stably tethered structure comprising an IgG antibody attached to two AD2 moieties of SEQ ID NO: 4 and four antigen-binding antibody fragments of the same or different IgG with each fragment attached to a DDD2 moiety of SEQ ID NO: 2; the AD2 moieties bound to the DDD2 moieties.

The four antigen-binding antibody fragments can be Fab fragments.  In particular, these Fab fragments can be the Fab fragments of humanized antibody hMN-14 that binds to CEA, humanized antibody hA20 that binds to CD20, humanized antibody hLL2 that binds to CD22, humanized antibody hL243 that binds to HLA class II, humanized antibody hCC49 that binds to TAG-72, humanized antibody hLL1 that binds to CD74, humanized antibody hPAM4 that binds to MUC 1, humanized antibody hRS7 that binds to EGP-1, humanized antibody hR1 that binds to IGF1R, anti-CD 14, anti-CD 111, adalimumab, infliximab, omalizumab, palivizumab, and humanized antibody hMN-15 that binds to CEA.

The abbreviation "AD" in claim 1 refers to the Anchoring Domain of A-kinase anchoring proteins (AKAPs), while "DDD" refers to the Dimerization and Docking Domain of cyclic-AMP-dependent protein kinase (PKA).  These two domains cooperate in this Dock-and-Lock (DNL) technology.

According to a recent paper authored by the inventors of the '787 patent (and others), the Dock-and-Lock technology is:

[A] new approach to develop targeting molecules for improved cancer imaging and therapy.  It involves the use of a pair of distinct protein domains involved in the natural association between cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and A-kinase anchoring proteins (AKAPs).  The dimerization and docking domain found in the regulatory subunit of PKA and the anchoring domain (AD) of an interactive AKAP are each attached to a biologic entity, and the resulting derivatives, when combined, readily form a stably tethered complex of a defined composition that fully retains the functions of the individual constituents.

Another recent patent assigned to IBC Pharmaceuticals, U.S. Patent No. 7,521,056, relates to the same technology as the '787 patent.  These two patents may be the first drawn to the PKA/AKAP Dock-and-Lock technology.

Other similar, so-called Dock-and-Lock systems are known.  For example, scientists at SibTech, Inc. published a report in 2006 about such a system "based on mutated fragments of human RNase I that spontaneously bind to each other and form a conjugate with a disulfide bond between complimentary cysteine residues."  Each of the mutated RNase I fragments may be independently linked to functionally heterogeneous compounds.