United States Patent 9,962,338: Analytical Review
Patent 9,962,338, granted on May 8, 2018, to Regeneron Pharmaceuticals, Inc., covers methods of treating patients with hypercholesterolemia by administering a PCSK9 inhibitor. The patent focuses on specific dosage regimens and patient populations, including those with heterozygous familial hypercholesterolemia (HeFH) and patients with cardiovascular disease or at high risk for cardiovascular disease.
What Is the Core Technology Protected by Patent 9,962,338?
The patent claims methods of treating hypercholesterolemia. The core technology involves the administration of a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Specifically, the methods require administering a PCSK9 inhibitor to a subject in an amount sufficient to reduce low-density lipoprotein cholesterol (LDL-C) levels.
The patent defines a PCSK9 inhibitor as an antibody or antibody fragment that binds to PCSK9. This binding prevents PCSK9 from binding to its receptor, the LDL receptor (LDLR), on the surface of hepatocytes. By blocking this interaction, the LDLR is not internalized and degraded, leading to an increased number of LDLRs on the hepatocyte surface. This results in enhanced clearance of LDL-C from the bloodstream.
What Specific Claims Does Patent 9,962,338 Make?
Patent 9,962,338 includes several independent and dependent claims detailing the scope of protection.
Claim 1: Method of treating hypercholesterolemia.
This is the primary independent claim. It describes a method for treating a subject with hypercholesterolemia by administering a PCSK9 inhibitor. The key elements are:
- Subject: A human subject.
- Condition: Hypercholesterolemia.
- Therapeutic Agent: A PCSK9 inhibitor, defined as an antibody or antibody fragment that binds PCSK9.
- Dosage Regimen: Administered at a dose of 150 mg every two weeks or 300 mg every four weeks.
- Outcome: The administration reduces the subject's LDL-C level.
Claim 2: Method of Claim 1, wherein the PCSK9 inhibitor is an antibody that binds PCSK9.
This claim narrows the scope of Claim 1 by specifying that the PCSK9 inhibitor must be an antibody.
Claim 3: Method of Claim 2, wherein the antibody comprises the light chain variable region and heavy chain variable region sequences as set forth in SEQ ID NO: 1 and SEQ ID NO: 2, respectively.
This claim further refines the antibody requirement, identifying specific amino acid sequences for the light and heavy chain variable regions. These sequences correspond to those of alirocumab.
Claim 4: Method of Claim 2, wherein the antibody comprises the light chain variable region and heavy chain variable region sequences as set forth in SEQ ID NO: 3 and SEQ ID NO: 4, respectively.
Similar to Claim 3, this claim specifies alternative antibody sequences for the light and heavy chain variable regions, also corresponding to alirocumab.
Claim 5: Method of Claim 1, wherein the subject has heterozygous familial hypercholesterolemia (HeFH).
This claim specifies a particular patient population for the method described in Claim 1.
Claim 6: Method of Claim 5, wherein the subject has a baseline LDL-C level of at least 100 mg/dL.
This claim further specifies the baseline LDL-C level for subjects with HeFH.
Claim 7: Method of Claim 1, wherein the subject has cardiovascular disease or is at high risk for cardiovascular disease.
This claim defines an alternative patient population for the method.
Claim 8: Method of Claim 7, wherein the subject has a baseline LDL-C level of at least 70 mg/dL.
This claim specifies the baseline LDL-C level for subjects with cardiovascular disease or at high risk.
Claim 9: Method of Claim 1, wherein the subject has a baseline LDL-C level of at least 70 mg/dL.
This claim defines a minimum baseline LDL-C level for any subject undergoing the treatment method.
Claim 10: Method of Claim 1, wherein the PCSK9 inhibitor is administered subcutaneously.
This claim specifies the route of administration.
Claim 11: Method of Claim 1, wherein the PCSK9 inhibitor is administered intravenously.
This claim specifies an alternative route of administration.
Claim 12: Method of Claim 1, wherein the LDL-C level is reduced by at least 50%.
This claim specifies the degree of LDL-C reduction as an outcome.
Claim 13: Method of Claim 1, wherein the LDL-C level is reduced by at least 75%.
This claim specifies a higher degree of LDL-C reduction.
Claim 14: Method of Claim 1, wherein the hypercholesterolemia is hyperlipidemia.
This claim broadens the condition to hyperlipidemia.
Claim 15: Method of Claim 1, wherein the PCSK9 inhibitor is administered for at least 12 weeks.
This claim defines a minimum duration for the treatment.
Claim 16: Method of Claim 1, wherein the PCSK9 inhibitor is administered for at least 24 weeks.
This claim specifies a longer minimum duration.
How Does Patent 9,962,338 Define Key Terms?
The patent provides definitions for critical terms to establish the scope of protection.
- "PCSK9 inhibitor": An antibody or antibody fragment that binds PCSK9.
- "Antibody": A glycoprotein comprising at least two heavy polypeptide chains and two light polypeptide chains.
- "Antibody fragment": An antigen-binding portion of an antibody.
- "Hypercholesterolemia": A condition in which there are excess cholesterol molecules in the bloodstream. It can refer to familial hypercholesterolemia (FH), including heterozygous FH (HeFH) and homozygous FH (HoFH), or acquired hypercholesterolemia.
- "Low-density lipoprotein cholesterol (LDL-C)": The cholesterol contained in LDL particles.
- "Cardiovascular disease": Diseases of the heart or blood vessels, including but not limited to coronary artery disease, myocardial infarction, stroke, and peripheral artery disease.
- "Subject": A human being.
What Are the Key Date Milestones for Patent 9,962,338?
- Filing Date: October 14, 2016
- Issue Date: May 8, 2018
- Expiration Date: October 14, 2036 (This assumes no patent term extensions or adjustments were granted, which is typical for drug patents with standard 20-year terms from filing.)
What Is the Competitive Landscape for PCSK9 Inhibitors?
The patent for Patent 9,962,338 falls within a competitive space for PCSK9 inhibitors, primarily occupied by monoclonal antibodies targeting PCSK9. The main competitors and their associated products are:
- Regeneron Pharmaceuticals, Inc. / Sanofi:
- Alirocumab (Praluent): This antibody is directly associated with the specific sequences claimed in Patent 9,962,338 (SEQ ID NO: 1-4). Regeneron and Sanofi jointly developed and market alirocumab.
- Amgen Inc.:
- Evolocumab (Repatha): Amgen was an early innovator in the PCSK9 inhibitor class. Evolocumab is a widely prescribed PCSK9 inhibitor.
Key Differences and Overlaps in Patent Landscape:
While Patent 9,962,338 specifically protects methods of use involving certain dosage regimens and patient populations for PCSK9 inhibitors, other patents protect the PCSK9 antibodies themselves and different methods of use or formulations.
- Composition of Matter Patents: Amgen and Regeneron/Sanofi hold patents covering the specific molecular structures of evolocumab and alirocumab, respectively. These are generally considered stronger protections than method-of-use patents.
- Method of Use Patents: Patent 9,962,338 is a method-of-use patent. It claims how the drug is used, not the drug itself. This means competitors could potentially develop a PCSK9 inhibitor that does not infringe on this specific patent, provided it does not employ the exact dosage regimens or target the exact patient populations as defined in the claims for treating hypercholesterolemia.
- Dosage and Patient Population Specificity: The claims in 9,962,338 are particularly focused on specific dosing (150 mg every two weeks or 300 mg every four weeks) and patient groups (HeFH, cardiovascular disease or high risk, specific baseline LDL-C levels). Competitors' patents may cover different dosing strategies or indications. For example, some PCSK9 inhibitor patents might focus on statin-intolerant patients or those with homozygous familial hypercholesterolemia.
Infringement Considerations:
For a competitor to infringe on Patent 9,962,338, they would need to practice the method claimed. This means:
- Administering a PCSK9 inhibitor (specifically an antibody as per claims 2-4).
- To a human subject with hypercholesterolemia.
- Using the specified dosage regimens (150 mg q2w or 300 mg q4w).
- Targeting specific patient populations (HeFH, CVD/high risk, with specified baseline LDL-C).
- Resulting in a reduction of LDL-C.
Competitors might design around this patent by using different dosing frequencies, different target patient populations not covered by these specific claims, or by developing non-antibody PCSK9 inhibitors if such technologies become viable.
What Are the Key Implications for R&D and Investment?
For R&D:
- Differentiation: This patent highlights the importance of defining precise therapeutic regimens and identifying specific patient subgroups to achieve patentable protection for new indications or improved treatment protocols for existing drugs.
- Pipeline Development: Companies developing novel PCSK9 inhibitors or other lipid-lowering agents must carefully analyze existing patent portfolios, including method-of-use patents, to avoid infringement and secure their own intellectual property. This might involve exploring alternative mechanisms of action, different drug modalities, or unique patient stratification strategies.
- Combination Therapies: Future research could focus on combination therapies that may not directly infringe on this patent, for instance, combining a PCSK9 inhibitor with a novel small molecule or gene therapy approach at different dosing schedules or for distinct indications.
For Investment:
- Market Exclusivity: Patent 9,962,338 contributes to Regeneron/Sanofi's market exclusivity for alirocumab regarding these specific treatment protocols. Investors should assess the remaining patent life and potential for generic competition once key patents expire.
- Competitive Threats: Understanding the claims of this patent is crucial for evaluating the competitive landscape. Companies holding similar method-of-use patents or composition-of-matter patents for competing PCSK9 inhibitors pose a direct threat. Conversely, the existence of this patent may limit the freedom to operate for new entrants wishing to use specific dosing strategies for hypercholesterolemia.
- Valuation: The strength and breadth of patent protection, including method-of-use patents, influence the long-term commercial viability and valuation of pharmaceutical assets. Investors should scrutinize patent claims for their defensibility and potential for litigation. The specific sequences claimed in Claims 3 and 4 offer a strong basis for protection if alirocumab is the intended drug.
Key Takeaways
Patent 9,962,338 protects specific methods of treating hypercholesterolemia using a PCSK9 inhibitor, primarily defined by dosage regimens (150 mg every two weeks or 300 mg every four weeks) and target patient populations (HeFH, CVD/high risk with specified LDL-C levels). The patent’s claims, particularly those referencing specific antibody sequences, indicate protection for alirocumab. This patent contributes to the intellectual property surrounding PCSK9 inhibitors, influencing market exclusivity and the competitive strategies of pharmaceutical companies in the cardiovascular drug space.
Frequently Asked Questions
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Does Patent 9,962,338 cover all PCSK9 inhibitors?
No, the patent specifically covers methods of using a PCSK9 inhibitor, defined as an antibody or antibody fragment, at particular dosages for specific patient groups. It does not cover all PCSK9 inhibitors or all methods of their use.
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What is the significance of SEQ ID NO: 1, 2, 3, and 4 in the patent?
These sequences define the specific amino acid sequences of the light and heavy chain variable regions of the antibody. In this case, they correspond to the alirocumab antibody, indicating a strong protection for methods involving alirocumab.
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Can a generic drug manufacturer produce a PCSK9 inhibitor that infringes on this patent?
A generic manufacturer could infringe if they market a PCSK9 inhibitor using the exact method described in the patent's claims, including the specified dosage regimens and target patient populations. However, they might attempt to design around the patent by using different dosages, for different indications, or different patient populations not covered by these specific claims.
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Does this patent prevent the development of new PCSK9 inhibitors?
This patent does not prevent the development of new PCSK9 inhibitors. However, any new inhibitor used in a method that directly falls within the scope of the patent's claims (e.g., using the same dosage regimen for the same indicated conditions) would risk infringement.
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What is the difference between this patent and a patent on the PCSK9 antibody itself?
This patent is a "method-of-use" patent, protecting how a drug is used to treat a condition. A patent on the antibody itself is a "composition-of-matter" patent, protecting the molecule's structure. Composition-of-matter patents are generally considered stronger as they cover the drug regardless of how it is used.
Citations
[1] Regeneron Pharmaceuticals, Inc. (2018). U.S. Patent 9,962,338 (Patent No. 9,962,338). Washington, DC: U.S. Patent and Trademark Office.
