United States Patent 8,455,536: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
The United States Patent 8,455,536, hereafter referred to as the '536 patent, is a crucial component of the intellectual property portfolio related to apremilast, a drug used primarily for the treatment of psoriasis. This patent, held by Amgen, is one of several that protect the formulation, preparation, and use of apremilast. Here, we delve into the scope, claims, and the broader patent landscape surrounding this patent.
Background on Apremilast
Apremilast, marketed under the brand name Otezla, is an oral medication used to treat moderate to severe plaque psoriasis and active psoriatic arthritis. It is a phosphodiesterase 4 (PDE4) inhibitor, which works by reducing inflammation in the body[1].
Patent Overview
The '536 patent, titled "Method of Treating Psoriasis with Stereomerically Pure Apremilast," was granted to Amgen and is set to expire on March 19, 2023[2].
Claims of the '536 Patent
The '536 patent includes several claims that define the scope of protection for Amgen's invention.
Claim 1
Claim 1 is a method claim that describes the use of stereomerically pure apremilast for treating psoriasis. This claim sets the foundation for the subsequent claims by specifying the use of a particular enantiomer of apremilast.
Claim 6
Claim 6 is a dependent claim that further narrows down the method described in Claim 1. It specifies that the stereomerically pure compound comprises greater than about 97% by weight of the (+) isomer based on the total weight percent of the compound. This level of purity is critical for the efficacy and safety of the drug[1].
Crystal Forms and Pharmaceutical Compositions
The patent also includes claims related to specific crystal forms of apremilast and solid pharmaceutical compositions containing these crystal forms. For example, Claim 15 recites a solid pharmaceutical composition comprising the crystal form of any one of the claims 1 through 13[1].
Patent Scope and Validity
The scope of the '536 patent is defined by its claims, which have been subject to various legal challenges.
Anticipation and Obviousness
The district court has ruled that the claims of the '536 patent were not anticipated by prior art references. Additionally, the court found that the claims were not obvious at the time of the invention, rejecting arguments that the combination of prior art references would have made the claimed invention obvious[1].
Double Patenting
Defendants in litigation have also argued that the '536 patent was invalid due to obvious-type double patenting (ODP) over another Amgen patent, the '283 patent. However, the court determined that the difference in expiration dates between the two patents was due to statutorily authorized time extensions and not due to prosecution gamesmanship or improper conduct. Therefore, the court did not apply the doctrine of ODP[1].
Patent Landscape
The '536 patent is part of a larger portfolio of patents related to apremilast.
Related Patents
Other patents in this portfolio include U.S. Pat. Nos. 7,427,638, 7,893,101, 8,093,283, and 10,092,541, among others. These patents cover various aspects of apremilast, including its preparation, crystal forms, and pharmaceutical compositions[2].
Expiration Dates
The expiration dates of these patents vary, with some set to expire in 2023 and others extending to 2028 and beyond. For instance, the '638 patent expires on February 16, 2028, while the '541 patent expires on May 29, 2034[2].
Litigation and Enforcement
Amgen has actively enforced its patents against generic manufacturers. For example, Amgen sued Dr. Reddy’s Laboratories, Sandoz, and Zydus Pharmaceuticals for infringement of several patents, including the '536 patent. The district court has generally ruled in favor of Amgen, upholding the validity and infringement of these patents[1].
Impact on Generic Manufacturers
The '536 patent and related patents pose significant barriers to entry for generic manufacturers seeking to produce apremilast.
ANDA Filings
Generic manufacturers must file Abbreviated New Drug Applications (ANDAs) with the FDA, which often trigger patent litigation. For instance, Zydus's proposed ANDA product was found to infringe Amgen's patents, including the '536 patent[1].
Bioequivalence and Therapeutic Equivalence
To gain FDA approval, generic versions must demonstrate bioequivalence and therapeutic equivalence to the reference listed drug (RLD), in this case, Otezla. However, the specific claims of the '536 patent, particularly those related to the purity and crystal forms of apremilast, make it challenging for generics to avoid infringement[2].
Conclusion
The United States Patent 8,455,536 is a critical component of Amgen's intellectual property strategy for protecting its drug apremilast. The patent's claims, particularly those related to the stereomerically pure compound and specific crystal forms, have been upheld in court against various challenges. This patent, along with others in the portfolio, ensures Amgen's market exclusivity for Otezla until the patents expire.
Key Takeaways
- Patent Scope: The '536 patent covers the use of stereomerically pure apremilast for treating psoriasis, with specific claims related to purity levels and crystal forms.
- Validity: The patent has been upheld against challenges of anticipation, obviousness, and double patenting.
- Related Patents: Part of a larger portfolio including U.S. Pat. Nos. 7,427,638, 7,893,101, 8,093,283, and 10,092,541.
- Litigation: Amgen has successfully enforced these patents against generic manufacturers.
- Impact on Generics: The patent poses significant barriers to entry for generic manufacturers due to its specific claims and the need to demonstrate bioequivalence and therapeutic equivalence.
FAQs
What is the primary use of the drug protected by the '536 patent?
The primary use of the drug protected by the '536 patent is the treatment of moderate to severe plaque psoriasis and active psoriatic arthritis.
What is the significance of the (+) isomer in the '536 patent?
The (+) isomer is significant because the patent specifies that the stereomerically pure compound must comprise greater than about 97% by weight of this isomer, which is crucial for the drug's efficacy and safety.
How has Amgen enforced its patents related to apremilast?
Amgen has enforced its patents through litigation against generic manufacturers, such as Dr. Reddy’s Laboratories, Sandoz, and Zydus Pharmaceuticals, and has generally been successful in upholding the validity and infringement of these patents.
What are the challenges faced by generic manufacturers in producing apremilast?
Generic manufacturers face challenges in avoiding infringement of Amgen's patents, particularly those related to the purity and crystal forms of apremilast, and must demonstrate bioequivalence and therapeutic equivalence to the reference listed drug.
When does the '536 patent expire?
The '536 patent is set to expire on March 19, 2023.
Sources
- Finnegan: “Show More of You”: Amgen v. Sandoz, Battling it Out on Amgen’s Otezla Drug.
- FDA: Apremilast Tablets - accessdata.fda.gov.
- Hoover Institution: Patent Claims and Patent Scope.
- Google Patents: Process for the preparation of apremilast - US10287248B2.
- FDA: Apremilast Tablets - accessdata.fda.gov (2021).
