All Submissions | J. Saba Submissions | Physics Site Links | Home Page |
| Email: James Saba |

GSJ: Received Feb. 27, 2006:
http://wbabin.net/saba/saba61.htm
Receptor Crosslinking Utilizing Different Monoclonal Antibodies
James Saba
As shown in Figure 1, an important characteristic of an antibody is its ability to crosslink a target with multiple identical epitopes.

Monoclonal antibodies (mAbs) have found enormous utility, and hold special promise in the war on cancer. It has been recognized, that under certain circumstances, the efficacy of mAbs would be enhanced if a target protein having only one epitope were crosslinked into an aggregate of more than two targets. The present invention is a proposal to achieve this crosslinking wherein each of two different mAbs is directed to a different epitope of the target protein.
Figure 2 exemplifies the process using two different multiple mAbs and a target present on a cancer cell.

For simplicity only four targets are shown. Conceivably such crosslinking of targets could initiate a cell signaling pathway, or activate complement.
While similar results might be expected from bispecific antibodies, the synthesis of such antibodies is more complex.
Figure 3 presents another interesting means of crosslinking multiple identical target molecules. Therein a target-binding molecule comprising multiple epitopes is first contacted with target, subsequently an antibody recognizing these epitopes is provided. Notice further that targeting different target proteins, using different adaptors with the same epitopes, would allow precise crosslinking of these different target proteins with one mAb.

Conceivably the antibodies the above examples could be conjugated to other molecules such as drugs, toxins or growth factors, and crosslinking could initiate cellular uptake.
While use of the invention in therapeutics is the primary objective, it is also has utility in diagnostics and technology.
If it should be that the above invention is indeed novel, any patentable rights I may have I freely give away. It is hoped that others will honor the invention as delineated by the following claims.
Claims
2) The process of claim 1, wherein the target is a virus or cell surface protein.
3) A process for crosslinking multiple target molecules comprising contacting target molecules with target-binding adaptors which comprise multiple identical epitopes, then providing an antibody to this epitope.
4) The process of claim 3, wherein the target molecules are virus or cell surface proteins.
5) A kit for performing any of the above process claims.
1)
Carbohydrate-binding molecules inhibit viral
fusion and entry by crosslinking membrane
glycoproteins.
Leikina, et al Nat Immunol. 2005
Oct;6(10):995-1001. Epub 2005 Sep 11
Of course, it would be obvious to form more branched crosslinked aggregates than exemplified in Figures 2 & 3, simply by using more than two mAbs, or an adaptor with more than 2 epitopes.
While the number of different soluble protein targets, such as anthrax toxin, do not appear as numerous as membrane associated protein targets, the present invention may find utility by aiding in vivo clearance of these soluble protein targets.
-----
Addendum 3/1/06
The following references have just been discovered, and teach many of the processes as described above. However from what I've read. they do not grasp nor have claimed the fundamental functioning of mAb combinations as envisioned above, nor the general applicability of the processes.
1)
Monoclonal antibodies to two epitopes of beta-human
chorionic gonadotropin for the treatment of cancer.
2)
Combined approach to treatment of cancer with hCG
vaccines.
3)
Combined approach to treatment of cancer with hCG
vaccines.
------
Addendum 3/5/06
Claims
1) A process of crosslinking identical proteins using
a bispecific antibody whose paratopes recognize
different epitopes on the protein.
3) The process of claim 2, wherein the protein is
soluble
4) The process of claim 3, wherein the protein is a
toxin, interleukin, cytokine, hormone, or interferon.
5) The process of claim 2, wherein the protein is a
membrane associated, and the bispecific antibody
effects is aggregation.
6) The process of claim 5, wherein the protein resides
on a virus, or a cell which has been infected or
transformed.
Inversen, et al (AVI Biophara) Curr Opin Mol Ther.
2003 Apr;5(2):156-60
US Patent Appl 20020164338 Nov 7, 2002
Iversen; PL US Patent 6,764,680 Filed, July
26, 2001, Issued July 20, 2004