US Drug Patent RE39071: Claim Scope, Daptomycin Coverage, Expiration, Litigation, and Generic Risk

US Reissue Patent RE39,071 was a principal patent in the Cubicin (daptomycin) patent estate. Its claims covered specified A21978C cyclic-peptide compounds, including C5-C14 N-acyl variants, compositions containing daptomycin and related A21978C components, pharmaceutical formulations, dosage ranges, and a pH-dependent separation process. The patent expired on September 24, 2018, and no enforceable exclusivity remains under RE39,071.

What drug and technology does US RE39071 protect?

US RE39,071 protects compositions related to the A21978C family of cyclic lipopeptide antibiotics. Daptomycin is the clinically relevant A21978C cyclic peptide used in Cubicin and generic daptomycin injection.

The claims distinguish among:

Claim subject	Claims	Principal limitation
Isolated formula 1 compound	1, 3-6, 16	C5-C14 alkanoyl group; D-alanine and D-serine
Isolated formula 2 compound	2, 7-11	C5-C14 alkanoyl group; D-alanine and D-serine
Antibacterial compositions	12-13	Formula 1 or formula 2 compound with a vehicle
Treatment methods	14-15, 17	Administration to animals or humans
Three-component antibiotic compositions	18-20	Formula 1, formula 2 and formula 3 A21978C compounds
Treatment methods using combinations	21-25	Animal and human dosing
Pharmaceutical formulations	26-28, 30-31	Defined impurity levels, daptomycin content and dosing
Separation process	29	Separation at a solution pH below 4 or above 6

The formula drawings are essential to identifying the exact structures. The supplied claim text omits those drawings, so the analysis of formula 1 and formula 2 is based on the textual limitations and the A21978C context rather than a reconstruction of each chemical structure.

What chemical structures are covered by RE39071?

What does the C5-C14 alkanoyl limitation mean?

Claims 1 and 2 require an alkanoyl substituent with five to 14 carbon atoms. The dependent claims narrow that range to particular acyl groups:

Claim 4: octanoyl
Claim 5: nonanoyl
Claims 6 and 16: decanoyl, including n-decanoyl
Claim 8: octanoyl for formula 2
Claim 9: nonanoyl for formula 2
Claim 10: decanoyl for formula 2
Claim 11: undecanoyl for formula 2

The claims also require that the alanine and serine residues have D stereochemistry. That stereochemical requirement excludes otherwise similar compounds containing L-alanine, L-serine or unspecified stereochemistry where the claim requires D configuration.

The practical chemical scope is therefore narrower than a general claim to all lipopeptide antibiotics or all daptomycin analogs. It is directed to specified A21978C-related structures with defined peptide stereochemistry and N-acyl chain length.

Does RE39071 claim daptomycin itself?

The combination claims expressly identify formula 3 as an A21978C cyclic peptide with an n-decanoyl group. In the commercial context, that limitation corresponds to daptomycin-containing material. Claims 18, 20, 26 and 30 then require the presence of formula 1 and formula 2 related compounds in defined proportions relative to the formula 3 cyclic peptide.

The patent therefore had two commercially relevant protection layers:

Claims to specific A21978C-related compounds.
Claims to daptomycin compositions containing controlled amounts of those related compounds.

This distinction mattered because a generic manufacturer could avoid a compound claim while still facing risk under a composition claim if its product contained the claimed components in the claimed concentrations.

What formulations are protected by US RE39071?

Claims 18 through 31 are the main formulation and product-composition provisions.

What impurity limits are claimed?

Claims 18, 20, 26 and 30 require the combined amount of the formula 1 and formula 2 compounds to be less than 6 weight percent. Claims 19, 28 and 31 narrow that threshold to 2.5 weight percent or less.

The claims can be summarized as follows:

Limitation	Claimed range
Combined formula 1 and formula 2 content	Less than 6 wt%
Narrower impurity threshold	Less than or equal to 2.5 wt%
Formula 3 A21978C cyclic peptide in claim 26	About 0.1-90 wt%
Narrower formula 3 range in claim 27	About 10-30 wt%
Animal dose in claim 23	About 0.1-100 mg/kg
Narrower animal dose in claim 24	About 1-30 mg/kg
Human dose in claim 25	About 100 mg-1 g/day

The composition claims do not merely require daptomycin. They require a particular combination of A21978C components and specified content limits. A product containing only highly purified formula 3 material could present a different infringement analysis from a product containing the claimed formula 1 and formula 2 components at the required levels.

What manufacturing process is protected?

Claim 29 covers a product made by separating formula 1, formula 2 and formula 3 compounds from a solution containing them, where the pH is:

Below 4; or
Above 6.

The claim is a product-by-process limitation attached to the composition claims. Its commercial relevance depends on whether the accused product has the claimed composition and whether the manufacturing history can be established as falling within the recited separation process.

The broad pH exclusion of the interval from 4 through 6 creates a process distinction rather than a universal manufacturing monopoly. Processes using pH 4-6 would not satisfy that literal limitation, although other claim elements and infringement doctrines would still require analysis.

How strong was the patent estate under RE39071?

What are the strongest claims?

The strongest commercial claims were likely the combination and formulation claims, particularly claims 18, 19, 26, 27, 28, 30 and 31.

Their strength came from the combination of:

A defined formula 3 A21978C compound;
Defined formula 1 and formula 2 related compounds;
A quantitative impurity ceiling;
Pharmaceutical or antibacterial use;
Specific dose or formulation limitations in some claims.

These limitations create a technically specific infringement test. They also provide potential design-around routes if a competitor can produce a product with different related-compound content, a different purification profile, or a different composition that does not meet the claimed thresholds.

What are the weaker or narrower claims?

Claims 1 and 2 are chemically limited to the specific formula structures, D-alanine and D-serine, and a C5-C14 alkanoyl group. Claims 3-11 narrow the scope further by identifying particular acyl chains.

Claims 14, 15, 17, 21, 22 and 25 are method claims. Their practical enforcement value depends on the approved label, actual use, and the ability to establish that a generic manufacturer induced the claimed administration or dosing regimen.

The claims are not a broad patent on every use of daptomycin, every daptomycin formulation, or every method of treating bacterial infection.

When did RE39071 expire?

Event	Date
Original A21978C-related patent family filings	1980s
FDA approval of Cubicin/daptomycin	September 2003
RE39071 reissue	March 27, 2007
Listed patent expiration	September 24, 2018
Current status	Expired

Reissue patent term is tied to the term of the original patent and does not create a new patent term merely because the patent was reissued. The September 24, 2018 expiration date is the commercially relevant endpoint reported for RE39071 in the daptomycin patent estate and FDA patent records.[1][2]

Patent-term extension and regulatory exclusivity must be evaluated separately from reissue status. RE39071 did not provide a current post-2018 barrier to generic daptomycin approval or launch.

What was the Orange Book status of RE39071?

RE39071 was listed in connection with Cubicin, the FDA-approved daptomycin product. The Orange Book listing supported the submission of patent certifications by ANDA applicants, including Paragraph IV certifications challenging listed patents.[1]

The listing did not mean that every claim in RE39071 covered every generic daptomycin product. Orange Book listing establishes the regulatory patent-certification framework. Actual infringement depended on the asserted claims and the composition, process and label of the proposed generic product.

Daptomycin is an injectable antibacterial product, not a small-molecule oral solid-dose product. The relevant regulatory pathway was an ANDA for a parenteral generic product, with pharmaceutical equivalence, bioequivalence and quality requirements focused on the injectable formulation.

Which companies challenged the Cubicin patent estate?

The principal generic challenges involved companies seeking approval for daptomycin injection, including Hospira, Teva and other ANDA sponsors. Cubist Pharmaceuticals and related entities asserted daptomycin patents in Hatch-Waxman litigation.

A key case was Cubist Pharmaceuticals, Inc. v. Hospira, Inc., 805 F.3d 1112 (Fed. Cir. 2015). The litigation involved Cubicin-related patents and addressed infringement and validity issues associated with daptomycin products.[3]

The litigation record illustrates the central risk for generic applicants: even where the active ingredient was known, patents directed to purity, related A21978C components, formulations, manufacturing and approved uses could delay approval or require settlement.

What Paragraph IV challenges affected generic daptomycin?

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable or will not be infringed by the ANDA product. For daptomycin, Paragraph IV challenges focused on the remaining Cubicin patent estate rather than the already expired early composition patents.

The commercial outcome was a series of patent settlements and litigation resolutions that allowed generic daptomycin products to enter before or around the expiration of the last significant listed patents. Generic daptomycin approvals began in 2016, with multiple manufacturers entering the market before RE39071's September 2018 expiration under the terms applicable to their approvals and settlements.[1][4]

A Paragraph IV challenge to RE39071 would have required analysis of:

Whether the generic product contained formula 1 and formula 2 components;
Whether those components were present below 6 wt% or at or below 2.5 wt%;
Whether the proposed product contained the claimed n-decanoyl formula 3 compound;
Whether the manufacturing process used the claimed pH separation step;
Whether the proposed label induced the claimed methods of treatment.

What settlement agreements affected daptomycin generic entry?

Cubist used patent litigation and settlement agreements to manage generic entry before the expiration dates of the listed patents. The commercial terms of individual agreements were not uniform and depended on the generic applicant, the patents challenged and the agreed launch date.

The settlements reduced the likelihood of an immediate at-risk launch while preserving eventual generic competition. They also reflected the limited remaining life of the estate: a settlement involving a patent expiring in 2018 had materially less economic value than a settlement involving a newly issued patent with a longer term.

The relevant antitrust and regulatory issue in any settlement analysis is whether the agreement included a payment or other restriction that delayed entry beyond the patent's lawful exclusionary period. The Federal Trade Commission has treated pharmaceutical patent settlements as a recurring antitrust subject, but RE39071's expiration means those historical arrangements no longer create current exclusivity.[5]

How does RE39071 compare with other daptomycin patents?

Patent category	Commercial subject	Status relevant to RE39071
Early A21978C composition patents	Core antibiotic compounds	Expired before or around initial Cubicin commercialization
RE39071	A21978C compounds, impurity-controlled compositions, formulations and process	Expired September 24, 2018
Purification and manufacturing patents	Removal or control of related compounds	Historically important to ANDA litigation
Method-of-treatment patents	Daptomycin dosing and administration	Separate infringement analysis
Later formulation patents	Injectable stability, excipients or presentation	Must be reviewed independently from RE39071
Regulatory exclusivity	NDA-based FDA exclusivity	Separate from patent term

RE39071 should therefore be analyzed as one part of the Cubicin estate, not as the sole daptomycin patent. The key commercial barriers were cumulative. A generic applicant could face different risk profiles under active-ingredient, formulation, process and method-of-use patents.

What biosimilar risk exists for daptomycin?

Daptomycin is a chemically characterized cyclic peptide antibiotic administered as an injectable product. Generic competition proceeds through the ANDA pathway rather than the biosimilar pathway used for biological products regulated under section 351(k) of the Public Health Service Act.

The principal post-expiration risk is generic substitution and price competition, not biosimilar interchangeability. Once RE39071 and other blocking patents expired or were resolved, manufacturers could compete through ANDA approvals subject to FDA quality and equivalence requirements.

What was the commercial exposure from RE39071?

Cubicin became a major product for Cubist Pharmaceuticals. Merck acquired Cubist in 2015 in a transaction valued at approximately $9.5 billion, with Cubicin as a central commercial asset.[6]

Cubicin annual sales reached approximately $1.5 billion in 2015 before generic erosion. The expiration and settlement schedule for the daptomycin estate therefore had material revenue implications for Cubist and, after the acquisition, Merck. Generic entry reduced pricing power and shifted demand from branded Cubicin to lower-priced daptomycin injection products.

The value of RE39071 was greatest before 2016, when the patent supported litigation leverage and helped protect the commercial formulation. Its direct revenue value fell sharply after generic entry and ended when the patent expired in 2018.

What generic launch scenarios existed under RE39071?

Three launch scenarios were commercially relevant:

At-risk launch before final patent resolution.
A generic applicant could launch before expiration after a favorable court decision or by accepting infringement risk.
Settled launch.
The applicant could launch on an agreed date, often before the listed patent's expiration, subject to settlement terms.
Post-expiration launch.
The applicant could launch without RE39071 creating an exclusionary barrier after September 24, 2018.

The composition claims created the greatest risk where the generic injectable reproduced the claimed A21978C impurity profile. A manufacturing design-around could reduce risk under claim 29 or the quantitative composition claims, but it would not automatically avoid separate daptomycin patents.

What geographic coverage did RE39071 have?

RE39071 was a United States patent. Its enforceable rights were limited to the United States and did not directly control manufacturing, sale or use in Europe, Japan, China or other jurisdictions.

The corresponding A21978C and daptomycin patent families required separate country-by-country review. International patent terms, national-phase prosecution, supplementary protection certificates and local litigation outcomes could differ materially from the US position.

Key Takeaways

RE39071 covered specified A21978C-related compounds with C5-C14 alkanoyl groups and D-alanine/D-serine stereochemistry.
Its principal commercial claims covered combinations of daptomycin-related formula 1 and formula 2 compounds with an n-decanoyl A21978C cyclic peptide.
The principal impurity thresholds were less than 6 weight percent and, in narrower claims, less than or equal to 2.5 weight percent.
Claim 29 covered a separation process performed at pH below 4 or above 6.
The patent expired on September 24, 2018.
RE39071 is no longer a current US exclusivity barrier to generic daptomycin.
Historical Paragraph IV litigation focused on the composition, purity, manufacturing and method-of-use layers of the Cubicin patent estate.
Daptomycin competition is an ANDA generic issue, not a conventional biosimilar issue.
Current freedom-to-operate analysis must examine later daptomycin formulation, manufacturing and method patents separately.

FAQs

Is RE39071 still enforceable against a daptomycin manufacturer?

No. RE39071 expired on September 24, 2018, so it no longer provides an enforceable US patent exclusion right.

Does RE39071 cover all daptomycin products?

No. The patent contains specific structural, compositional, impurity, process and dosing limitations. A product must satisfy the relevant limitations of an asserted claim.

Is a product with less than 2.5% related compounds automatically outside RE39071?

No. The less-than-or-equal-to-2.5% threshold is one limitation in narrower claims. Other claim elements, including the identity of the compounds and the formula 3 cyclic peptide, must also be considered.

Can a manufacturer use a pH between 4 and 6 to avoid claim 29?

A process using a pH between 4 and 6 would not literally satisfy the recited pH condition of claim 29. The remaining composition claims and other daptomycin patents would require separate analysis.

Does FDA approval of generic daptomycin prove that the generic did not infringe RE39071?

No. FDA approval and patent infringement are separate issues. Approval can follow a Paragraph IV certification, a patent settlement, patent expiration or other regulatory resolution without a judicial determination that every asserted claim is invalid or not infringed.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations (Orange Book).
U.S. Patent and Trademark Office. (2007). United States Reissue Patent No. RE39,071, Antibiotic compositions.
Cubist Pharmaceuticals, Inc. v. Hospira, Inc., 805 F.3d 1112 (Fed. Cir. 2015).
U.S. Food and Drug Administration. (2003). Cubicin (daptomycin for injection) prescribing information.
Federal Trade Commission. (2013). Pay-for-delay: How drug company pay-offs cost consumers billions.
Merck & Co., Inc. (2015). Annual report and acquisition disclosures regarding Cubist Pharmaceuticals.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	1749388	⤷ Start Trial
Australia	613640	⤷ Start Trial
Bulgaria	47349	⤷ Start Trial
Canada	1315229	⤷ Start Trial
European Patent Office	0294990	⤷ Start Trial
Hungary	201120	⤷ Start Trial
Hungary	T47154	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE39071

Summary for Patent: RE39071