`
`https://web.archive.org/web/20000303232942/http://www.pdl.com/Guid...
`
`The human body naturally produces millions of antibodies, proteins that fight disease by binding to specific targets on the surfaces of
`bacteria or viruses. In the 1970s, scientists first developed techniques to immunize mice with a foreign organism and clone (isolate)
`and grow single cells that pump out antibodies against the intruder. Despite their initial promise, these mouse monoclonal antibodies
`have fallen short as therapeutics. They are rapidly eliminated from the body and so must be infused into patients almost daily. More
`important, the body's own antibodies mount an immune reaction (known as a human anti-mouse antibody or HAMA response) against
`the mouse antibody, rendering it ineffective for further therapy.
`
`To overcome these limitations, PDL uses computer modeling and genetic engineering to convert mouse antibodies into human-like
`SMART (TM) Antibodies.
`
`DNA from cells producing a mouse antibody is isolated and placed in a sequencing machine to determine the chemical structure of the
`genes that encode the antibody. Using the genetic code, the amino acids composing the antibody itself are then determined.
`
`Proprietary computer software compares the amino acid sequence of the mouse antibody to the sequences of antibodies whose
`structure has been determined using X-ray diffraction, and then builds a 3-dimensional model of the key part of the mouse antibody.
`
`Click Here to see a computer modeling demonstration of PDL's humanization strategy.
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`IMMUNOGEN 2083, pg. 1
`Phigenix v. Immunogen
`IPR2014-00676
`
`
`
`PDL's Humanized Antibody Technology
`
`https://web.archive.org/web/20000303232942/http://www.pdl.com/Guid...
`
`The minimum number of mouse amino acids (shown in red and dark blue) identified as necessary for binding to the target are
`combined with amino acids from a human antibody (light blue).
`
`The chemical structure of the genes to make the new SMART Antibody are programmed into a DNA synthesizer to synthesize the
`genes.
`
`The genes are inserted into a mammalian cell, which produces the antibody. In the lab, a humanized anti-herpes antibody blocks the
`virus from spreading from infected cells (dark spots, left); without the antibody, the virus infects all cells (right).
`
`Additional Technologies:
`Human Antibodies
`
`Novel Antibiotics
`
`Small Molecules
`
`Additional
`Information:
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`2 of 3
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`12/28/2014 5:40 PM
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`IMMUNOGEN 2083, pg. 2
`Phigenix v. Immunogen
`IPR2014-00676
`
`
`
`PDL's Humanized Antibody Technology
`
`https://web.archive.org/web/20000303232942/http://www.pdl.com/Guid...
`
`I N T lll'l lf At C t0\11
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`ma~unehmoo~m~
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`5 captures
`27 Jan 00 - 8 Jan 01
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`Go
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`JAN
`~
`1999
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`JUN
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`...
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`2001 ~
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`3 of 3
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`12/28/2014 5:40 PM
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`IMMUNOGEN 2083, pg. 3
`Phigenix v. Immunogen
`IPR2014-00676
`
`
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