HERCEPTIN PROTEIN PURIFICATION IPR (BIOSIMILAR INTER PARTES REVIEW)

Hospira has filed a petition for an IPR (IPR2016-0183) (inter partes review) of Genentech’s U.S. Patent No. 7,807,799, which is directed to methods of purifying antibodies.  The claims of the '799 Patent cover any protein that has a CH2/CH3 region, including Genentech’s trastuzumab (Herceptin^®).  The Patent Trial and Appeal Board (PTAB) has not yet made a decision on the petition.  The ’799 Patent claims a method of purifying a protein which comprises a CH2/CH3 region by carrying out protein A affinity chromatography at a temperature in the range of about 10 °C to about 18 °C.  Hospira mainly relies on the following two references for teaching the limitations of the claims of the ‘799 Patent:

Claim Limitations	WO 95/22389
1. A method of purifying a protein which comprises a CH2/CH3 region	A method for the purification of an IgG antibody . . .
comprising subjecting a composition comprising said protein to protein A affinity chromatography	A method for the purification of an IgG antibody . . . comprising sequentially subjecting the medium to (a) Protein A affinity chromatography.
at a temperature in the range from about 10 °C to about 18 °C.	The process in its most preferred embodiment consists of three purification steps (Protein A affinity, cation exchange, and hydrophobic interaction chromatography) . . . All steps are carried out at room temperature (18 – 25 °C).
5. The method of claim 1 wherein the protein is an antibody.	A method for the purification of an IgG antibody . . .

Claim Limitations	Van Sommeren (22 Preparative Biochemistry 135 (1992))
1. A method of purifying a protein which comprises a CH2/CH3 region	The purification of immunoglobulins (IgG) . . .”
comprising subjecting a composition comprising said protein to protein A affinity chromatography	The purification of immunoglobulins (IgG), in particular mouse monoclonal antibodies (mabs), using affinity chromatography with protein A as ligand is very popular . . .
at a temperature in the range from about 10 °C. to about 18 °C.	The effect of temperature, 4°C versus ambient temperature (AT) (20-25°C), was studied for the mabs OT-hCG-1C, 4D, 3A, 6A and 7B and OT-HIV-4A and 4B . .
2. The method of claim 1 further comprising exposing the composition subjected to protein A affinity chromatography to a protease inhibitor	Whether or not degradation of the IgG molecule occurs, depends among other factors on pH and subclass of the mab. However, if required, the activity of cathepsin D can be inhibited by addition of pepstatin A
5. The method of claim 1 wherein the protein is an antibody.	The purification of immunoglobulins (IgG) . . .