By James Love
On November 17, 2017, Genentech, a subsidiary of the giant Swiss drug company Roche, together with City of Hope, a charity, filed a complaint in a U.S. District Court, seeking an injunction to block introduction of a Pfizer biosimilar version of Herceptin (INN: trastuzumab), as well as other remedies to infringement, including compensation for Roche’s lost profits if competition occurs. The complaint (Genentech vPfizer, 17-cv-1672, U.S. District Court, District of of Delaware (Wilmington), filed November 17, 2017) illustrates the complexity of the patent landscape on a drug placed on the market more than 19 years ago and the need for compulsory licensing of patents.
Trastuzumab is a very important drug for the treatment of breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+). My wife was treated with trastuzumab for several years, and is currently on a follow-on Roche treatment named Kadcyla, which is a combination of trastuzumab and the small molecule DM1. (DM1 is an NIH funded drug now off patent).
The early development of trastuzumab was dramatic, and documented in such accounts as Robert Bazell’s very readable book, Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer, published in 1998, and the 2008 movie Living Proof, starting Harry Connick, Jr.. Bazell’s book was referred in the New York Times and the New England Journal of Medicine. The Bazell book and the Living Proof movie provide a dramatic account of the unwillingness of Genentech to invest in the research that led to the approval of trastuzmab, and the role of the Revlon Foundation to support Dr. Dennis Slamon’s critical work at UCLA.
In the complaint, Roche asserts it has spent billions on the development of the drug, but provides no details. The company certainly did not spent much on the initial approval. Like many other oncology products, first approval of Herceptin was based upon evidence from a fairly small number of patients enrolled in clinical trials.
The development of the product has also benefited from more than a half billion dollars of grants from the NIH that mention trastuzumab (See Table 2) and tax credits associated with two orphan drug designations.
Since entering the market in 1998, Roche has now earned more than $70 billion for Herceptin, and another $3 billion for Kadcyla, the follow-on product.
Despite being a drug introduced in the previous century, Roche claims that Pfizer’s biosimilar “will infringe at least” forty patents (See Table 1) including patents filed as late as 2015 that are in effect until 2035.
The Genentech/Roche/City of Hope complaint refers to eight categories for the patents, including:
- The Cabilly Patents
- The ’213 Patent
- The Combination Chemotherapy Patents
- The Method of Administration Patents
- The Acidic Variants Patents
- Combination Therapy with Perjeta
- HER2 Diagnostic Patents
- Cell Culture, Purification, and Antibody Manufacturing Patents
Herceptin is a remarkable drug, but after enjoying 19 years as a monopoly and $70 billion in sales, one might think enough is enough, as regards the rewards to the Roche shareholders.
Pfizer may be able to avoid an injunction and defend itself from infringement claims from the 40 patents, but policy makers need to reflect on the barriers to competition that can exist 19 years and $70 billion into a legal monopoly.
A robust compulsory licensing authority is needed in the United States, so that when global revenues are massive and excessive, as is the case for Herceptin, relevant to the rewards necessary to induce investments, the government can effectively end the legal monopoly and permit competition among suppliers to drive down prices. To the extent that there are useful patented inventions that the biosimilar manufacturer will use, compulsory licenses can provide reasonable royalties that are rationally related to the value the inventions add.
The U.S. does not currently have such legislation.
Table 1: Patents asserted in the litigation.
- U.S. Patent No. 6,121,428,
- U.S. Patent No. 6,242,177,
- U.S. Patent No. 6,331,415,
- U.S. Patent No. 6,339,142,
- U.S. Patent No. 6,407,213,
- U.S. Patent No. 6,417,335,
- U.S. Patent No. 6,489,447,
- U.S. Patent No. 6,586,206,
- U.S. Patent No. 6,610,516,
- U.S. Patent No. 6,620,918,
- U.S. Patent No. 6,627,196,
- U.S. Patent No. 6,716,602,
- U.S. Patent No. 7,371,379,
- U.S. Patent No. 7,390,660,
- U.S. Patent No. 7,449,184,
- U.S. Patent No. 7,485,704,
- U.S. Patent No. 7,501,122,
- U.S. Patent No. 7,807,799,
- U.S. Patent No. 7,846,441,
- U.S. Patent No. 7,892,549,
- U.S. Patent No. 7,923,221,
- U.S. Patent No. 7,993,834,
- U.S. Patent No. 8,044,017,
- U.S. Patent No. 8,076,066,
- U.S. Patent No. 8,314,225,
- U.S. Patent No. 8,425,908,
- U.S. Patent No. 8,440,402,
- U.S. Patent No. 8,460,895,
- U.S. Patent No. 8,512,983,
- U.S. Patent No. 8,574,869,
- U.S. Patent No. 8,633,302,
- U.S. Patent No. 8,691,232,
- U.S. Patent No. 8,710,196,
- U.S. Patent No. 8,771,988,
- U.S. Patent No. 8,822,655,
- U.S. Patent No. 9,249,218,
- U.S. Patent No. 9,428,766,
- U.S. Patent No. 9,487,809,
- U.S. Patent No. 9,493,744.
- U.S. Patent No. 9,714,293,
Table 2: RePORT Query on grants that reference trastuzumab
Data from Text Search: trastuzumab (and), Search in: Projects Admin IC: All, Fiscal Year: All Fiscal Years, November 23, 2017
| Fiscal Year | Projects | Total Funding | Sub Projects | Sub Project Funding |
|||
|---|---|---|---|---|---|---|---|
| 2001 | 5 | $1,151,302 | |||||
| 2002 | 8 | $2,671,092 | 4 | $474,284 | |||
| 2003 | 9 | $2,946,489 | 2 | $316,544 | |||
| 2004 | 7 | $2,556,980 | 2 | $8,640 | |||
| 2005 | 17 | $8,457,864 | 6 | $674,760 | |||
| 2006 | 16 | $8,625,487 | 9 | $746,619 | |||
| 2007 | 84 | $48,022,416 | 25 | $4,881,065 | |||
| 2008 | 90 | $46,744,992 | 36 | $7,557,057 | |||
| 2009 | 120 | $53,881,758 | 41 | $9,830,989 | |||
| 2010 | 105 | $45,506,129 | 37 | $10,406,122 | |||
| 2011 | 112 | $59,167,833 | 25 | $5,338,714 | |||
| 2012 | 123 | $65,641,621 | 26 | $6,557,562 | |||
| 2013 | 114 | $62,864,589 | 16 | $5,116,944 | |||
| 2014 | 115 | $42,777,063 | 16 | $5,045,661 | |||
| 2015 | 100 | $40,045,247 | 16 | $5,062,483 | |||
| 2016 | 96 | $43,067,013 | 14 | $3,791,454 | |||
| 2017 | 94 | $37,116,111 | 12 | $4,726,943 | |||
| Total | 1,215 | $571,243,986 | 287 | $70,535,841 | |||