G-CSF, rDNA/Sanofi
Lenograstim - Granocyte; Neutrogin; granulocyte colony stimulating factor, recombinant
Status - marketed internationally (ex-U.S.)
Organizations involved:
Sanofi Aventis S.A. – Manuf.; R&D; Tech.; Intl. mark.
Aventis Pharma AG – Former
Chugai Pharmaceutical Co. Ltd. – R&D; Tech.; Japan mark.
Ajinomoto Co., Ltd. –Patent dispute
Cross ref.: See the G-CSF entries, particularly filgrastim (Neupogen) (#158), for G-CSF-related information.
Description: Granocyte is a formulation of lenograstim or recombinant Chinese hamster ovary (CHO) cell expressed granulocyte-colony-stimulating factor (G-CSF) glycoprotein with a sequence substantially identical to human G-CSF. It is not marketed in the U.S. Lenograstim is the only glycosylated (due to mammalian cell expression) recombinant G-CSF available in Europe. The molecule is composed of approximately 4% carbohydrates. Lenograstim is "indistinguishable" from the 174 amino acid natural human G-CSF [which is hard to believe with curent analytical technologies]..
Nomenclature: G-CSF, rDNA/Sanofi [BIO]; lenograstim [INN]; Granocyte; [TR foreign]; Neutrogin [TR in Japan]
Companies.: Granocyte was developed by Rhone-Poulenc Rorer S.A., later Aventis Pharma (merged into Sanofi Aventis S.A. in late 2004), and Chugai Pharmaceuticals (part of the Roche Group). The product is manufactured and marketed in certain European and other countries by Sanofi Aventis S.A., and in Japan by Chugai.
Status: Granocyte is currently marketed in over 70 countries, including some in Europe (but not in most major market countries, presumably due to Amgen’s G-CSF patents, including those licensed from Sloan-Kettering Memorial Cancer Institute). Like Neupogen and Neulasta, it is used for treatment of chemotherapy-induced neutropenia, neutropenia following bone-marrow transplantation, and mobilization of autologous peripheral blood progenitor cells (PBPCs).
Granocyte was first approved in 1993 and remains the only glycosylated recombinant G-CSF available in some European countries. It has received European Union approval.
Tech. transfer: In Feb. 2007, Japan’s Intellectual Property High Court ruled in favor of Chugai in a patent infringement and invalidation suit involving Ajinomoto Co. Ltd., which filed a patent infringement suit with the Tokyo District Court in 2004 against Chugai alleging infringement by Neutrogin (lenograstim) of a process patent it owns. Ajinomoto’s patent was ruled invalid by the Japanese Patent Office in Sept. 2005. The court dismissed the suit in March 2006. Ajinomoto appealed both decisions, but the country’s highest court sided with Chugai.
Market: Worldwide 2009 sales by Roche, including Chugai, were CHF 385 million ($358 million), ~$347 million in 2008 and $308 million in 2007. 2006 worldwide sales as reported by Roche were CHF 379 million (~$311 million at 7/6/2007 exchange rate.
Companies involvement:
Full monograph
160 G-CSF, rDNA/Sanofi
Nomenclature:
Filgrastim [USAN INN BAN MESH]
r-metHuG-CSF [SY]
G-CSF, rDNA/Sanofi [BIO]
Lenograstim [FDA]
Granocyte [TR]
135968-09-1 [CAS RN]
granulocyte colony stimulating factor, recombinant [SY]
Neutrogin [TR in Japan]
molecular weight (kDa) = 19
FDA Class: Biologic BLA
Annual sales (2011, $millions) = $305
Annual sales (2010, $millions) = $357
Annual sales (2009, $millions) = $358
Annual sales (2008, $millions) = $347
Annual sales (2007, $millions) = $308
Biosimilars/biobetters Data
(Caution: Determining relevant patents, exclusivities and their expirations can be very complex and subjective!
Confirmatory studies are recommended before making business decisions based on these data.
U.S.A.
European Union (EU)
Biosimilars/biobetters-related U.S. Patents: 2013, based on 5,580,755 and 5,582,823; not approved, no biosimilars possible
U.S. Patent Expiration Year: 2013
U.S. Biosimilars Data Exclusivity Expiration:
U.S. Biosimilars Orphan Exclusivity Expiration:
U.S. Biosimilars Launchability Year:
U.S. Biobetters Launchability Year: 2013
Biosimilars/biobetters-related EU Patents: no EU centralized approval, no biosimilars possible; 1993, date of first launch in European countries, arbitrarily used as expiration date
EU Patent Expiration Year: 1993
EU Biosimilars Data Exclusivity Expiration:
EU Biosimilars Orphan Exclusivity Expiration:
EU Biosimilars Launchability Year:
EU Biobetters Launchability Year: 1993
Exclusivity add-ons from pediatric and new indication approvals have not been
taken into account. U.S. patent extensions, based on time in clinical trials, have been included, but not those in Europe (where SPCs are individually
issued by each country).
Single year data are presented, but the situation is rarely that simple. This includes determining the relevance of
patents, presuming these have been retrieved, which cna be highly subjective. The first 2 fields for the US and EU are text fields, often
including diverse patent information, including citing other sources' published dates for patent expirations.
Orphan exclusivity is simply 7 years in the U.S. and 10 years in the EU after initial approval, with it left to the user to check monographs for
actual approvals with orphan status. Similarly, data exclusivity expiration in the U.S. is 12 years and in the EU is 10 years after initial reference product
approval, when biosimilar applications can be approved.
Biosimilars launchability is the latest date of either patent, orphan or data
exclusivity, with any of these blocking approval and/or market entry. Biobetters, by definition products (bio)similar but different enough
to receive full, not biosimilar, approvals, have launchability dates the same as the patent expiration date, with these new/different products
not subject to reference product's orphan or data exclusivity.
Exclusive licensing of patents and other potential factors discussed in the full monographs that could, just as effectively as
patents held by the manufacturer, prevent or confound market entry were included in consideration of patent expiration.
Index Terms:
biopharmaceutical products
exempt from CBER lot release requirements
growth factors, hematopoietic
hamster source materials
recombinant DNA
rodent source materials
Chinese hamster ovary (CHO) cells
North American coral snake
EU200 Currently Approved in EU
UM999 Not Available/Not Marketed in US
US000 never filed/no plans
EM001 Marketed Product in EU
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