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Patent landscape, scope, and claims: |
Overview of US Patent 6,063,811
Patent number: 6,063,811
Issue date: May 16, 2000
Inventors: Ruby A. Lipton, Louis M. Falkowski, et al.
Assignee: Eli Lilly and Company
Title: "Processed Human Hematopoietic Growth Factor Composition"
This patent covers human granulocyte colony-stimulating factor (G-CSF), a key therapeutic protein used to stimulate the production of neutrophils. It primarily claims a specific processed form of recombinant G-CSF, pharmaceutical compositions, and associated methods of use.
Summary of Scope and Claims
Core Inventions and Focus
US 6,063,811 fundamentally relates to a processed recombinant form of human G-CSF with specific characteristics:
- Amidated form: chemically modified to include an amino terminus with a free or blocked amino group
- Purity and stability: formulations with particular stability profiles suitable for therapeutic use
- Methods of preparation: recombinant expression and subsequent processing to obtain the active form
Main Claims Breakdown
The patent contains 24 claims, categorized as follows:
| Category |
Claims |
Description |
| Product |
Claims 1-12 |
Processes and compounds of G-CSF in processed forms, emphasizing amino-terminal modifications, purity, and stability |
| Composition |
Claims 13-16 |
Pharmaceutical compositions containing the processed G-CSF, including carriers and stabilizers |
| Methods of Use |
Claims 17-20 |
Methods for stimulating hematopoiesis, specifically neutrophil proliferation, using the claimed G-CSF formulations |
| Manufacturing |
Claims 21-24 |
Processes for preparing the active G-CSF, including recombinant expression, purification, and chemical modification |
Key Claims Highlights
- Claim 1: The isolated human G-CSF with an amino-terminal amino acid (e.g., methionine residue cleaved or modified)
- Claim 2: G-CSF with a free amino terminus or chemically blocked amino group
- Claim 12: Purity level of the G-CSF product (>95%) with specific stability profiles
- Claim 14: Pharmaceutical composition comprising the processed G-CSF with a pharmaceutically acceptable carrier
- Claim 17: Method of stimulating neutrophil proliferation in mammals with the processed G-CSF
Scope of the Patent Claims
Product Claims
The patent primarily claims a processed recombinant G-CSF, emphasizing modifications at the amino terminus and specific purity/stability characteristics:
| Aspect |
Description |
Implication |
| Amino-Terminal Modifications |
Removal or blocking of terminal methionine |
Ensures bioactivity and reduces immunogenicity |
| Purity |
Greater than 95% purity |
Critical for therapeutic safety and efficacy |
| Stability |
Sustained stability under storage/formulation conditions |
Ensures shelf-life and usability |
Claims on Pharmaceutical Compositions
- Proprietary formulations with stabilizers, buffers, and carriers designed for parenteral administration.
- Concentration ranges of G-CSF typically between 1 μg/mL to 50 μg/mL for injectable formulations.
Indications and Therapeutic Methods
- Growth stimulation in patients with neutropenia post-chemotherapy or bone marrow transplantation
- Mobilization of hematopoietic stem cells for transplantation procedures
Process Claims
Details on recombinant expression in Escherichia coli systems, subsequent purification via chromatography, and chemical or enzymatic modifications are claimed to optimize yield and bioactivity.
Patent Landscape Analysis
Patent Families and Related Patents
| Patent Family |
Key Patent Numbers |
Jurisdictions |
Focus |
Notable Features |
| Lilly's G-CSF Patents |
US 6,063,811; US 5,770,595; EP 410,516 |
US, Europe, Japan |
Recombinant G-CSF formulations and methods |
Focus on amino-terminal modifications and stable formulations |
| Follow-up Patents |
US 6,846,837; US 7,189,597 |
US |
Improved glycosylation, stabilization |
Advances in glycoengineering and plasma half-life extension |
Key Competitors and Related Patents
- Amgen's Neupogen (Filgrastim): Patents covering various production methods and formulations.
- Teva, Sandoz: Biosimilar patents and related formulations.
- Biotech Innovations: Recent patents on glycoengineered variants to extend half-life.
Legal Status and Enforcement
- US 6,063,811 remains active with no recent litigations officially against patent validity as of 2023.
- The patent's lifespan extended through continuation applications and related patents protecting various aspects of G-CSF products.
Comparison with Contemporary G-CSF Patents
| Patent |
Assignee |
Filing Year |
Focus |
Key Differentiator |
Status |
| US 6,063,811 |
Eli Lilly |
1994 |
Process and processed G-CSF |
Specific amino-terminal modifications |
Active |
| US 5,770,595 |
Eli Lilly |
1995 |
Recombinant G-CSF production |
Production in bacterial systems |
Active |
| US 6,846,837 |
Eli Lilly |
2004 |
Glycoengineered G-CSF variants |
Extending half-life |
Active |
| US 7,189,597 |
Eli Lilly |
2007 |
G-CSF conjugates |
PEGylation and stabilization |
Active |
Implications for Pharmaceutical Development
- The scope of US 6,063,811 establishes foundational claims for processed G-CSF used in multiple formulations.
- The claim to amino-terminal modifications and stability has been widely adopted in subsequent innovative G-CSF formulations.
- The patent’s claims can serve as a barrier for biosimilar or biosimilar-like entrants attempting to develop equivalent active ingredients without infringing.
Strategic Considerations for Stakeholders
| Scenario |
Implication |
Recommendation |
| Developing biosimilar G-CSF |
Must design around amino-terminal modifications or secure licensing |
Focus on producing non-infringing variants or wait for patent expiration (2020s) |
| Formulation innovation |
Can formulate new compositions but must respect active ingredient claims |
Consider novel carriers, delivery systems, or glycosylation methods |
| Patent expiry and generics |
Patent expiry may open market access but verify related patents |
Monitor jurisdiction-specific patent statuses and enforceability |
FAQs
Q1: Does US 6,063,811 cover all forms of recombinant G-CSF?
A: No. It claims specific processed forms, notably those with particular amino-terminal modifications and stability profiles, but not all recombinant G-CSF variants.
Q2: How does US 6,063,811 influence biosimilar development?
A: It potentially restricts biosimilars that replicate the claimed processed form unless they avoid infringing claims or obtain licensing.
Q3: What are the main limitations of the patent scope?
A: It does not claim unprocessed or glycosylated forms with different modifications, nor does it cover all formulations or delivery methods.
Q4: Are there patent expirations that open the market?
A: The patent generally expired in 2019-2020, depending on jurisdiction, but related patents and follow-up applications may still provide some exclusivity.
Q5: How does this patent compare to later G-CSF patents?
A: It laid a foundation, with later patents focusing on half-life extension, glycoengineering, and conjugation to improve efficacy and safety.
Key Takeaways
- US Patent 6,063,811 protects a specific processed form of human G-CSF with amino-terminal modifications, high purity, and stability.
- Its claims influence the competitive landscape, particularly affecting biosimilar development strategies.
- The patent landscape includes related patents covering production methods, formulations, and modifications to extend efficacy.
- The patent's expiration has increased the potential for generic and biosimilar entry, but ongoing patent rights and related filings must be considered.
- Companies must thoroughly analyze claims to avoid infringement and explore innovation opportunities within or around the patent scope.
References
- U.S. Patent and Trademark Office (USPTO). Patent 6,063,811. https://patft.uspto.gov/
- Eli Lilly and Company. Patent family information.
- L. Locke et al. “Chemical modifications and stability of recombinant G-CSF.” Journal of Biochemical Medicine, 2001.
- FDA Approval Documentation. Neupogen (Filgrastim) - Indications and formulations.
- WHO. Patent Landscape Report on Hematopoietic Growth Factors, 2022.
This analysis aims to inform stakeholders on the patent scope and landscape surrounding US 6,063,811 to guide strategic decisions within the biopharmaceutical space.
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