Details for Patent: 9,624,250

Which drugs does patent 9,624,250 protect, and when does it expire?

Patent 9,624,250 protects SIVEXTRO and is included in two NDAs.

This patent has forty-one patent family members in twenty-eight countries.

Summary for Patent: 9,624,250

Title:	Forms of R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate
Abstract:	A crystalline form of crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, methods of making the crystalline form and pharmaceutical compositions comprising the crystalline form are useful antibiotics. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the crystalline form may be used in antibiotics.
Inventor(s):	Katharina Reichenbacher, Robert J. Duguid, Jacqueline A. Ware, Douglas Phillipson
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US14/959,412
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 9,624,250: Tedizolid Phosphate Crystal, Formulation, Process and Use-Claim Analysis

US Patent 9,624,250 protects selected crystalline particles of tedizolid phosphate, related pharmaceutical compositions, sodium-salt lyophilized injectable products, crystallization processes, and antibacterial uses. Its core protection is narrower than a basic compound patent: infringement generally turns on the claimed crystalline form, impurity or co-component profile, particle-size limitation, manufacturing route, or use of the resulting product.

The patent concerns tedizolid phosphate, the active pharmaceutical ingredient in Sivextro, approved by the FDA in 2014 for acute bacterial skin and skin-structure infections caused by susceptible Gram-positive organisms, including MRSA [1].

What drug does US Patent 9,624,250 protect?

US 9,624,250 covers crystalline tedizolid phosphate rather than the fundamental tedizolid molecular scaffold.

Tedizolid phosphate is the phosphate prodrug of tedizolid. The claimed chemical name is:

(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

The patent’s commercial relevance arises from the relationship between:

• The crystalline solid form of tedizolid phosphate.
• The disodium phosphate salt used in injectable formulations.
• Particle size and solid-state purity.
• Acid-mediated conversion to the claimed crystalline particles.
• Lyophilized powders for injection.
• Treatment of infections caused by MRSA and vancomycin-resistant Enterococci.
• Oral and parenteral pharmaceutical compositions.

The patent does not appear, from the supplied claims, to claim all forms of tedizolid, all salts of tedizolid phosphate, or every use of tedizolid as a broad composition-of-matter patent would.

What are the independent claims in US 9,624,250?

The principal independent claims are claims 1, 7, 8, 10, 13, 15 and 24.

Claim	Subject matter	Practical scope
1	Crystalline particles containing at least about 96 wt% tedizolid phosphate and defined PXRD peaks	Core solid-state claim
7	Pharmaceutical composition containing the particles of claim 1	Product formulation claim
8	Reaction mixture containing the particles and a base	Intermediate or preparation-state claim
10	Lyophilisate of the reaction mixture with specified disodium-phosphate chemistry	Injectable formulation claim
13	Treatment of bacterial infection using claim 7 composition	Method-of-use claim
15	Lyophilized injectable powder made by converting the dihydrogen phosphate with sodium hydroxide and lyophilizing	Process-defined product claim
24	Pharmaceutical composition containing particles made by contacting a salt with acid solution	Acid-conversion process claim

The chemical structures and Markush members omitted from the supplied text are material to the exact scope of claims 1-5 and 10-12. The broad claim architecture can be analyzed, but the missing structures prevent a complete element-by-element construction of those dependent claims.

What does claim 1 cover?

Claim 1 is the principal crystalline-form claim. It requires all of the following:

1. Crystalline particles.
2. At least about 96% by weight of the specified tedizolid phosphate compound.
3. An X-ray powder diffraction pattern containing peaks at approximately:
   • 14.7°
   • 15.2°
   • 16.6°
   • 20.3°
   • 26.8°
   • 28.2°
4. A remainder containing at least one compound from a specified group.

The PXRD limitations are central. A product containing tedizolid phosphate but lacking the claimed diffraction pattern should not literally meet claim 1. Conversely, a generic or follow-on manufacturer could face risk if its solid exhibits the same required peaks, even if it uses a different crystallization solvent or manufacturing sequence.

The "at least about 96% by weight" limitation creates an additional purity threshold. It may exclude lower-purity mixtures, amorphous material, or products with materially higher levels of related substances. The word "about" creates interpretive flexibility and potential litigation over the acceptable analytical margin.

The remainder limitation is also important. Claims 1-5 appear to define specific residual compounds or related substances. Those chemical lists are absent from the supplied text. They may operate as impurity-profile limitations rather than broad excipient limitations.

How do claims 2 through 6 narrow the crystalline-form protection?

Claims 2 through 5 add progressively narrower residual-compound requirements. Their commercial value depends on the omitted chemical structures.

Claim 6 adds a particle-size requirement:

• Median volume diameter of at least about 1.0 micrometer.

This limitation may distinguish the claimed material from milled, micronized, nanocrystalline, or precipitation-derived tedizolid phosphate. Particle size can affect filtration, suspension behavior, dissolution, bulk density, injectability, and lyophilization performance.

A product with the same PXRD pattern but a median volume diameter below approximately 1.0 micrometer may avoid claim 6 while remaining within claim 1. A product with a larger particle size but a different crystal form may avoid both claims.

What formulations are protected by US 9,624,250?

Oral pharmaceutical compositions

Claim 7 covers a pharmaceutical composition containing the claim 1 crystalline particles and a pharmaceutically acceptable carrier, excipient or diluent.

Claim 14 narrows claim 7 to an oral dosage form. Potential commercial embodiments include tablets, capsules, powders, granules and oral suspensions, although the claim language supplied does not limit the formulation to a specific excipient system.

The formulation claim is dependent on the crystalline-particle limitation. A composition containing a different tedizolid phosphate form may fall outside claim 7.

Lyophilized injectable products

Claims 10 through 12 address a lyophilisate made from a reaction mixture containing the crystalline material and a base. Claim 9 identifies sodium hydroxide as one base.

Claim 15 separately covers a lyophilized powder for injection made by:

1. Mixing the dihydrogen phosphate compound with sodium hydroxide solution.
2. Forming the disodium salt.
3. Lyophilizing the resulting solution.

Claim 16 covers use of that powder to treat bacterial infection.

This creates two related but distinct enforcement routes:

• Composition claims directed to the lyophilized product.
• Process and product-by-process claims directed to how the injectable powder is made.

What is the scope of the antibacterial method claims?

Claims 13, 16 and 19 through 23 address treatment of bacterial infections.

The relevant narrowing sequence is:

Claim	Limitation
13	Administering claim 7 pharmaceutical composition to treat bacterial infection
16	Administering claim 15 lyophilized powder
17	Infection results from a Gram-positive bacterium
18	MRSA or VRE
19	Claim 13 limited to Gram-positive infection
20	MRSA or VRE
21	1 mg to 500 mg of tedizolid phosphate
22	5 mg to 200 mg
23	About 200 mg

Claims 21-23 are dose-specific. They may be relevant to a product using the claimed crystalline composition at a 200 mg dose, which corresponds to the commercial strength associated with Sivextro therapy.

The method claims are narrower than an unrestricted claim to treating bacterial infections because they depend on the specific formulation or crystalline material. They also include specific pathogen and dosage limitations in the dependent claims.

When does US Patent 9,624,250 expire?

The patent’s nominal expiration is expected to fall in late 2032, based on a 2012 priority framework and the standard 20-year patent term measured from the relevant nonprovisional filing date. The exact enforceable date depends on the patent’s priority chain and any patent-term adjustment recorded by the USPTO.

Event	Date or status
Subject matter	Tedizolid phosphate crystalline particles and related products
U.S. patent	9,624,250
Issue date	April 18, 2017
Nominal term	Expected to extend into 2032
FDA approval of Sivextro	June 20, 2014
NME exclusivity	Generally expired in 2019
QIDP-related extension	The product received qualified infectious disease product treatment, extending regulatory exclusivity beyond the ordinary NME period
Patent-term extension	No extension should be assumed without confirmation in the current USPTO and Orange Book records

Regulatory exclusivity and patent term are separate. FDA exclusivity can block approval of an ANDA or 505(b)(2) application even after a patent expires. Conversely, patent protection can continue after regulatory exclusivity ends.

What is the Orange Book status of US 9,624,250?

The supplied claim text does not establish the patent’s current Orange Book listing status, use code, or delisting history. Patent 9,624,250 is relevant to the Sivextro patent landscape because it covers commercial crystalline, formulation and injectable-product subject matter, but an Orange Book listing must be determined from the current FDA Approved Drug Products with Therapeutic Equivalence Evaluations database [2].

For an ANDA applicant, the critical questions are:

• Whether 9,624,250 is listed against the relevant Sivextro dosage form.
• Whether the listing covers oral tedizolid phosphate, injectable tedizolid phosphate, or both.
• Whether FDA assigns a use code to the method claims.
• Whether the listed claims are composition, formulation or method-of-use claims.
• Whether the patent has been removed, expired or disclaimed.

A Paragraph IV certification would create a potentially material litigation event if the patent remains listed and unexpired.

What Paragraph IV challenges and generic entry risks exist?

Tedizolid is a small molecule, so the principal generic pathway is an ANDA rather than a biosimilar application.

A generic applicant could pursue several strategies:

Form-specific design-around

The applicant could attempt to use:

• An amorphous form.
• A different polymorph.
• A hydrate or solvate not exhibiting the claimed PXRD pattern.
• A particle-size distribution below the claim 6 threshold.
• A different impurity profile.
• A different salt or neutral form, if pharmaceutically viable.

The key risk is that a different manufacturing route may still produce the same claimed crystal form. Process variation alone does not necessarily avoid a product claim.

Process design-around

For claim 15, a manufacturer could avoid the sodium-hydroxide conversion and lyophilization sequence. That would not automatically avoid claims 1, 7 or 10 if the resulting product independently meets their structural and analytical limitations.

Method-of-use certification

A generic applicant may use a section viii statement to carve out patented uses if the approved label and patent use code allow a lawful skinny-label strategy. That strategy is more difficult where the composition itself is patented and the commercial product cannot reasonably be sold without practicing the patented formulation claim.

How strong is the patent estate for tedizolid phosphate?

The estate is strongest against a manufacturer that reproduces the commercial solid form or injectable process. It is weaker against a technically differentiated product.

Risk factor	Assessment
Crystal-form specificity	Stronger than a broad formulation claim if PXRD reproducibility is clear
Purity threshold	Creates a measurable infringement limitation but may produce claim-construction disputes
PXRD peaks	Usually testable through routine analytical comparison
Particle-size limitation	Potentially useful but sensitive to measurement method and sampling
Oral composition claim	Depends entirely on use of the claimed crystal
Injectable process claim	Strong against the specified sodium-hydroxide and lyophilization route
Method claims	Narrow because they depend on the claimed product or formulation
Missing Markush structures	Prevents complete assessment of dependent-claim breadth
Biosimilar exposure	Not applicable because tedizolid is a small molecule
Manufacturing barrier	Moderate; solid-form control and impurity management may be more significant than synthetic complexity

Potential validity challenges could focus on anticipation or obviousness based on prior crystalline forms, routine salt conversion, predictable lyophilization, or routine selection of particle size. The patentee would likely argue that the claimed PXRD pattern, purity profile, residual compounds and injectable performance define a non-routine solid-state product.

What patent litigation affects Sivextro and tedizolid?

A complete litigation assessment requires the current PACER and USPTO records. The supplied materials identify no complaint, ANDA notice letter, settlement, consent judgment or license agreement involving 9,624,250.

The practical litigation triggers are:

• Paragraph IV certification against the patent.
• A generic product exhibiting the claimed PXRD pattern.
• Use of the sodium-hydroxide conversion and lyophilization process.
• Commercial sale of an oral formulation containing the claimed crystal.
• A 200 mg product labeled for MRSA or other covered Gram-positive infections.

No settlement terms or license rights can be inferred from the claims themselves.

Which companies compete with tedizolid?

Tedizolid competes primarily in Gram-positive and acute bacterial skin-infection markets.

Product	Active ingredient	Manufacturer or commercial sponsor	Relevance
Sivextro	Tedizolid phosphate	Merck	Originator product
Zyvox	Linezolid	Pfizer	Established oxazolidinone competitor
Vancomycin	Vancomycin	Multiple manufacturers	Hospital standard for serious Gram-positive infections
Dalvance	Dalbavancin	AbbVie	Long-acting intravenous therapy
Orbactiv	Oritavancin	Melinta	Long-acting intravenous therapy
Nuzyra	Omadacycline	Paratek	Broad-spectrum alternative
Fetroja and other agents	Various	Multiple manufacturers	Indication- and setting-specific competition

Tedizolid’s commercial differentiation includes once-daily dosing and a shorter treatment course in the approved acute bacterial skin and skin-structure infection indication. Linezolid remains the most direct oxazolidinone comparator.

How does US 9,624,250 compare with a basic tedizolid compound patent?

Patent type	Typical scope	Relevance to 9,624,250
Compound patent	Tedizolid chemical structure and analogs	Broader molecular protection
Salt patent	Tedizolid phosphate or disodium salt	Covers chemical form rather than a particular crystal
Crystal patent	PXRD-defined crystalline material	Focus of 9,624,250
Formulation patent	Tablet, injectable, excipient system or stability profile	Claims 7 and 10-15 overlap this category
Process patent	Salt conversion, crystallization or lyophilization	Claims 8, 15 and 24-27
Method patent	Treatment of defined infections or dosing regimens	Claims 13 and 16-23

A basic compound patent generally presents the largest theoretical barrier but may expire earlier. A later crystal or formulation patent can extend practical market protection if the approved product uses the claimed form and a generic cannot launch without reproducing it.

What are the key freedom-to-operate issues?

A generic or licensee should test the following before launch:

1. PXRD identity against the six listed peaks.
2. Tedizolid phosphate assay and the 96 wt% threshold.
3. Residual-compound profile under claims 1-5.
4. Median volume diameter under claim 6.
5. Use of sodium hydroxide in injectable manufacture.
6. Lyophilization of the resulting disodium salt solution.
7. Acid treatment using HCl with ethanol or tetrahydrofuran.
8. Whether the final product is oral, injectable or both.
9. Label language covering MRSA, VRE or other Gram-positive infections.
10. Current patent listing and any ANDA litigation.

Analytical testing should use validated PXRD methods, defined peak-matching tolerances and a documented particle-size methodology. Infringement may depend on test conditions, polymorph conversion during processing and whether the accused product is assessed before or after formulation.

Key Takeaways

• US 9,624,250 is principally a tedizolid phosphate solid-state and product patent.
• Claim 1 requires at least about 96 wt% of the specified compound plus a defined PXRD peak pattern.
• Claim 6 adds a median volume diameter of at least about 1.0 micrometer.
• Claims 7 and 14 cover pharmaceutical compositions, including oral dosage forms.
• Claims 10 and 15 target lyophilized injectable products and sodium-hydroxide conversion processes.
• Claims 13 and 19-23 cover treatment of bacterial infections, including MRSA and VRE, with specified dose ranges.
• Claims 24-27 cover acid-mediated preparation of the crystalline particles.
• The nominal patent term is expected to extend into 2032, subject to the recorded priority chain and patent-term adjustment.
• Generic risk is highest where the proposed product reproduces the commercial tedizolid phosphate crystal or injectable manufacturing route.
• Tedizolid is a small molecule; biosimilar rules do not apply.
• The supplied claim text omits chemical structures in several Markush limitations, preventing complete construction of claims 1-5 and 10-12.

FAQs

Does US 9,624,250 cover tedizolid itself?

No. The supplied claims focus on a crystalline tedizolid phosphate material and related formulations, processes and uses. They do not read as a simple unrestricted claim to every form of tedizolid.

Can a generic avoid US 9,624,250 by using a different solvent?

Not necessarily. A different solvent or crystallization sequence may still produce particles with the claimed PXRD pattern, purity and residual-compound profile. Product claims are not avoided solely by changing the manufacturing solvent.

Does the patent cover intravenous Sivextro?

It may cover certain lyophilized injectable tedizolid phosphate products and the sodium-hydroxide conversion process used to make them. Coverage depends on whether the commercial product satisfies every limitation of the applicable claims.

Is a 200 mg tedizolid product specifically claimed?

Yes. Claim 23 narrows the treatment method to administration of about 200 mg of the specified tedizolid phosphate compound, subject to the dependencies of claims 21 and 22.

Are MRSA and VRE both within the claimed treatment scope?

Yes. Claims 18 and 20 expressly identify methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci as covered Gram-positive infections.

References

1. U.S. Food and Drug Administration. (2014). Sivextro (tedizolid phosphate) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205435s000lbl.pdf

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files

3. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,624,250, crystalline particles and pharmaceutical compositions comprising the same. https://patents.google.com/patent/US9624250B2

4. U.S. Food and Drug Administration. (2012). Guidance for industry: 180-day exclusivity: questions and answers. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/180-day-exclusivity-questions-and-answers

5. U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. https://www.uspto.gov/patents/laws/patent-term-adjustment-patent-term-extension-prioritization-examination-recovery-act.

Drugs Protected by US Patent 9,624,250

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cubist Pharms Llc	SIVEXTRO	tedizolid phosphate	POWDER;INTRAVENOUS	205436-001	Jun 20, 2014		RX	Yes	Yes			Y	Y		METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA
Cubist Pharms Llc	SIVEXTRO	tedizolid phosphate	TABLET;ORAL	205435-001	Jun 20, 2014		RX	Yes	Yes			Y	Y		METHOD OF TREATING ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI) CAUSED BY DESIGNATED SUSCEPTIBLE BACTERIA

International Family Members for US Patent 9,624,250

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	2987
Australia	2010210627
Brazil	PI1008829
Canada	2751392
Chile	2011001855