Details for Patent: 7,144,861

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Summary for Patent: 7,144,861

Title:	Stabilized teriparatide solutions
Abstract:	A stabilized pharmaceutical composition in the form of a solution for parenteral administration of a parathyroid hormone is described wherein the therapeutically active ingredient is stabilized with a buffer and a polyol. Preferred preparations contain in an aqueous solution human PTH(1–34), mannitol, an acetate or tartrate buffering agent and m-cresol or benzyl alcohol as a preservative.
Inventor(s):	Chin-Ming Chang, Henry A. Havel
Assignee:	Eli Lilly and Co
Application Number:	US10/055,509
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,144,861
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 7,144,861: Claim Scope, Expiration, Orange Book Status, and Teriparatide Patent Landscape

US Patent No. 7,144,861 protects specific ready-to-use aqueous formulations of human parathyroid hormone (1-34), commonly known as teriparatide. Its core combination is teriparatide at 100-500 micrograms/mL, an acetate buffer at acidic pH, a polyol or carbohydrate stabilizer, a preservative, sterility, and direct parenteral administration. The patent also covers a specified mannitol/m-cresol formulation, its preparation method, and a sealed vial containing the non-reconstituted solution.

The patent was assigned to Eli Lilly and Company and was directed principally to the formulation used for Forteo. Its ordinary patent term has expired. The claims remain relevant for historical infringement analysis, patent-family mapping, and evaluation of later teriparatide products, but they do not provide current US exclusionary rights.

What does US Patent 7,144,861 protect?

The patent protects a product-and-process platform for a liquid, ready-to-administer teriparatide formulation.

Claim group	Protected subject matter	Principal limitations
Claims 1-8	Aqueous pharmaceutical solution	Teriparatide, acetate buffer, stabilizer, preservative, water, sterility
Claim 8	Specific formulation	0.25 mg teriparatide, 50 mg mannitol, 2.5 mg m-cresol, acetic acid, sodium acetate, and water per mL
Claims 9-11	Manufacturing method	Admixing and sterilizing without freeze-drying or reconstitution
Claims 12-15	Sealed vial	Sterile, ready-to-use, non-reconstituted teriparatide solution

The patent does not broadly claim teriparatide as a molecule. It claims a formulation and presentation of teriparatide.

What is the independent formulation claim?

Claim 1 requires all of the following:

1. Human parathyroid hormone (1-34).
2. A concentration of about 100-500 micrograms/mL.
3. An acetate buffer maintaining pH from 3 to 6.
4. A stabilizer selected from specified carbohydrates, polyols, or mixtures.
5. A parenterally acceptable preservative.
6. Water.
7. Sterility.
8. Readiness for parenteral administration to a human patient.

The claim is a combination claim. A formulation missing any required element would not literally fall within claim 1, although it could raise a doctrine-of-equivalents issue depending on the facts and the jurisdiction.

How narrow is claim 8?

Claim 8 is materially narrower than claim 1. It recites a defined formulation per 1 mL:

• 0.25 mg human parathyroid hormone (1-34)
• 50 mg mannitol
• 2.5 mg m-cresol
• 0.52 mg acetic acid
• 0.12 mg sodium acetate
• Water
• Sterility
• Readiness for parenteral administration

The nominal concentrations are:

Component	Amount per mL	Approximate concentration
Teriparatide	0.25 mg	250 micrograms/mL
Mannitol	50 mg	5% w/v
m-Cresol	2.5 mg	0.25% w/v
Acetic acid	0.52 mg	0.052% w/v
Sodium acetate	0.12 mg	0.012% w/v

Claim 8 is more vulnerable to design-around than claim 1 because it specifies the composition numerically. A formulation using benzyl alcohol instead of m-cresol, a different stabilizer, or materially different component quantities would require a separate infringement analysis.

What are the key claim limitations?

Teriparatide identity and concentration

The claims require human parathyroid hormone (1-34), not every parathyroid-hormone analog. Abaloparatide, full-length parathyroid hormone, PTH-related peptide, and other analogs are outside the literal identity limitation unless a court finds an equivalent.

The claimed concentration range is approximately 100-500 micrograms/mL. Claim 7 narrows this to 250 micrograms/mL. Concentration is likely measured in the finished solution, not merely by the amount loaded into a vial.

The word "about" introduces a range of practical variation. It does not eliminate the concentration limitation. The relevant question would be whether a product concentration outside the stated numerical range is reasonably understood as approximately within the claimed range, considering the specification, prosecution history, analytical precision, and commercial formulation practice.

Acetate or tartrate buffer

Claims 1-11 principally require an acetate buffer. Claims 12-15 permit an acetate or tartrate buffer system.

The buffer must maintain an acidic pH:

• Claims 1-8: pH 3-6.
• Claim 9: pH greater than 3 and less than 7.
• Claims 10-11: buffer concentration of about 2-100 mM.
• Claims 12-15: pH 3-6.

A phosphate-buffered, citrate-buffered, or unbuffered formulation would not literally satisfy the acetate-buffer limitation. Claim 12 is broader because it adds tartrate as an alternative.

Stabilizer

The stabilizer must be selected from the listed substances or mixtures:

• Glucose
• Trehalose
• Raffinose
• Sucrose
• Mannitol
• Sorbitol
• Inositol
• Glycerine or glycerol
• Propylene glycol

Claims 4 and 10 narrow the mannitol concentration to approximately 3-10% by weight. Claims 13-15 require mannitol, with claim 14 allowing approximately 1-20% and claim 15 narrowing the range to approximately 3-10%.

The stabilizer limitation creates a substantial design-around route. A later formulation using a stabilizer outside the list could avoid literal infringement, subject to equivalence analysis.

Preservative

The independent claims require a parenterally acceptable preservative. Claims 2, 3, 10, and 15 narrow the preservative to m-cresol or benzyl alcohol.

Claim 3 specifies m-cresol at approximately 0.3-1.0% by weight. Claim 8, however, recites 2.5 mg/mL, approximately 0.25% w/v. The apparent difference reflects the use of separate claim formulations and concentration conventions. Claim construction would require examination of the specification and prosecution history before treating the claims as interchangeable.

Sterility and ready-to-use status

The product claims require a sterile solution ready for parenteral administration. The claims do not cover a lyophilized powder requiring reconstitution in the same manner as a ready-to-use liquid.

Claims 9-15 emphasize the absence of freeze-drying or reconstitution. For a product claim, actual presentation and use would be central. A vial containing a dry cake plus diluent would be materially different from the claimed non-reconstituted aqueous solution.

How do the method claims differ from the product claims?

Claims 9-11 require a manufacturing method with two central steps:

1. Admixing teriparatide with the specified buffer, stabilizer, preservative, and water.
2. Sterilizing the solution for parenteral administration.

The method must produce teriparatide at approximately 100-500 micrograms/mL and must proceed without freeze-drying or reconstitution before patient use.

A method can infringe even if the resulting product is not sold under the same brand name. The relevant conduct would include the process used to manufacture the commercial solution. Evidence may include batch records, manufacturing instructions, validation documents, regulatory filings, and technical transfer materials.

The claim does not appear to require a particular sterilization technique in the text provided. It therefore potentially covers filtration, aseptic processing, or another qualifying sterilization approach, subject to the specification and prosecution record.

What formulation is specifically associated with Forteo?

The claimed formulation closely tracks the liquid Forteo presentation described in FDA labeling.

Attribute	Claimed or labeled formulation
Active ingredient	Teriparatide, human PTH (1-34)
Concentration	250 micrograms/mL
Delivery	Subcutaneous injection
Stabilizer	Mannitol
Preservative	m-Cresol
Buffer	Acetate system
Presentation	Multi-dose prefilled delivery device or ready-to-use liquid presentation

The FDA label identifies Forteo as a recombinant human parathyroid hormone analog containing teriparatide and describes the commercial injection as a preserved aqueous solution for subcutaneous use.[1]

The patent should not be treated as covering every teriparatide product merely because the product contains the same active ingredient. The combination of excipients, pH, concentration, sterility, and presentation controls the claim analysis.

When did US Patent 7,144,861 expire?

US Patent No. 7,144,861 issued on December 5, 2006. Public patent records identify an earliest priority date in the 2000 period and a standard US patent-term expiration in January 2021.[2][3]

Event	Date
Earliest priority period	2000
US application filing	2001
Patent grant	December 5, 2006
Expected ordinary expiration	January 2021
Current status	Expired

The exact expiration determination should be made from the USPTO Patent Center term calculation and any terminal disclaimer or patent-term adjustment record. The patent is no longer a current US barrier to launch.

Did pediatric exclusivity extend the patent?

Pediatric exclusivity can add six months to certain listed patents associated with an approved drug. It is distinct from patent term and must be confirmed from FDA Orange Book records and the applicable exclusivity listing.[4]

The commercial entry of generic or alternative teriparatide products after the 2020-2021 period indicates that the principal Forteo formulation barriers had ended or were no longer sufficient to block launch.

What was the Orange Book status?

The FDA Orange Book lists patents and exclusivity information for approved drug products. Forteo-related patent records included formulation and other patent rights associated with Eli Lilly's product.[4]

US Patent 7,144,861 was relevant to the Forteo formulation patent estate, but its expiration removed it as a current Orange Book patent barrier. An Orange Book listing does not itself establish validity or infringement. It identifies patent information submitted by the NDA holder and affects ANDA certification obligations while the patent remains listed and unexpired.

The likely certification framework during the active term would have included:

• Paragraph III certification if the applicant accepted delayed approval until expiration.
• Paragraph IV certification if the applicant asserted that the patent was invalid, unenforceable, or not infringed.
• A 30-month stay if the NDA holder filed timely patent litigation after a Paragraph IV notice, subject to statutory conditions.[5]

Were there Paragraph IV challenges to this patent?

The patent landscape for generic teriparatide included patent certifications and litigation risk involving the Forteo NDA and its listed patents. A Paragraph IV challenge would have focused on invalidity, non-infringement, or both.

The principal litigation issues likely to arise from these claims are:

Issue	Potential challenger position
Anticipation	Prior liquid PTH formulations disclosed the same components and ranges
Obviousness	It was predictable to combine acetate, mannitol, m-cresol, and teriparatide
Written description	Broad stabilizer and concentration ranges may lack full support
Enablement	The full scope may not be enabled across all excipients and ranges
Infringement	Product uses a different buffer, preservative, stabilizer, or concentration
Claim construction	Meaning of "about," "ready for parenteral administration," and "sterilizing"
Double patenting	Overlap with related Lilly formulation patents

The patent's expiration makes historical Paragraph IV analysis more important than current launch-blocking risk. Current parties would generally focus on whether a product infringed during the active term and whether damages remain available under the applicable limitation period.

How strong was the patent estate?

The estate was strongest against a product reproducing the commercial Forteo formulation:

• 250 micrograms/mL teriparatide
• Mannitol
• m-Cresol
• Acetate buffer
• Sterile aqueous liquid
• Ready-to-use presentation

It was weaker against products using formulation substitutions.

Product design	Likely literal coverage risk
250 micrograms/mL, mannitol, m-cresol, acetate, ready-to-use liquid	High
250 micrograms/mL, mannitol, benzyl alcohol, acetate	Moderate to high under claims 2 and 15, depending on ranges
Teriparatide with citrate buffer	Lower
Teriparatide with phosphate buffer	Lower
Lyophilized teriparatide requiring reconstitution	Lower
Teriparatide outside 100-500 micrograms/mL	Lower, subject to "about"
Abaloparatide	Low under the identity limitation
Full-length PTH (1-84)	Low under the active-ingredient limitation

Because several claims use open-ended transitional language such as "comprises," adding another excipient would not avoid infringement if every claimed element remained present.

What generic entry risks exist for teriparatide?

The principal US entry risks now arise from commercial competition and regulatory substitution, not from US Patent 7,144,861.

Generic and 505(b)(2) competition

Teriparatide products may proceed through abbreviated regulatory pathways depending on the product's characterization and reference product. The FDA has approved non-Forteo teriparatide injection products, including products that compete with Forteo in the osteoporosis market.[6]

A competing product can avoid the expired patent through:

• Different preservative selection.
• Different buffer chemistry.
• Different stabilizer.
• Different concentration.
• Different container or delivery device.
• A lyophilized or otherwise reconstituted presentation.
• A formulation that does not meet the claim's sterile ready-to-use limitations.

Biosimilar risk

Traditional biosimilar analysis is less direct for teriparatide than for large therapeutic proteins. Teriparatide is a 34-amino-acid peptide, and FDA approval pathways depend on the product's regulatory classification and reference-product framework. A competitor may therefore enter through an abbreviated drug application rather than a conventional BPCIA biosimilar pathway.

The practical risk is still substitution of a clinically equivalent teriparatide product. The relevant barriers include reference-product exclusivity, device compatibility, analytical comparability, manufacturing controls, and any unexpired formulation or device patents.

How does teriparatide compare with abaloparatide?

Abaloparatide is a distinct PTH receptor agonist marketed as Tymlos. It is not human PTH (1-34), and the active-ingredient limitation in US Patent 7,144,861 creates a substantial distinction.

Attribute	Teriparatide	Abaloparatide
Active ingredient	Human PTH (1-34)	Synthetic PTH-related peptide analog
Representative product	Forteo	Tymlos
Patent 7,144,861 coverage	Potentially applicable	Generally outside literal active-ingredient scope
Formulation competition	Strong generic pressure after expiration	Separate Radius patent estate
Regulatory pathway	Abbreviated teriparatide products	Separate product and patent analysis

The two products compete clinically in osteoporosis but do not share the same active-ingredient patent scope.

What manufacturing and IP barriers remain?

The expired patent does not remove all barriers to market entry. A teriparatide competitor still faces:

• Peptide synthesis or recombinant production controls.
• Aggregation and oxidation control.
• Aseptic filling.
• Preservative compatibility.
• Container-closure integrity.
• Stability testing.
• Delivery-device qualification.
• FDA chemistry, manufacturing, and controls review.
• Potential device patents.
• Trade secrets covering yield, purification, and formulation processes.
• Foreign patents with different expiration dates.

The formulation itself is relatively straightforward to describe, but peptide stability and sterile manufacturing can create meaningful operational barriers. Those barriers are commercial and regulatory rather than enforceable rights under the expired US patent.

What is the geographic coverage?

US Patent 7,144,861 covered the United States only. Related international applications and national-stage patents may have existed in Europe, Canada, Japan, and other markets, but foreign rights required separate validity, term, and maintenance-fee analysis.

US expiration did not automatically terminate corresponding foreign patents. A launch assessment outside the United States must review:

• National-phase patent numbers.
• Local patent-term rules.
• Supplementary protection certificates.
• Pediatric extensions.
• Local Orange Book equivalents.
• Pending divisional or continuation applications.
• Patent litigation in each jurisdiction.

Key Takeaways

• US Patent 7,144,861 claims ready-to-use sterile aqueous teriparatide formulations, not teriparatide as a molecule.
• The core claimed combination is teriparatide at 100-500 micrograms/mL, acidic acetate buffering, a listed stabilizer, a parenteral preservative, water, and direct parenteral administration.
• Claim 8 specifically targets a 250 micrograms/mL mannitol/m-cresol formulation associated with Forteo.
• Claims 9-11 cover preparation and sterilization without freeze-drying or reconstitution.
• Claims 12-15 cover a sealed vial containing a non-reconstituted sterile liquid.
• The patent's ordinary US term expired in or around January 2021.
• Historical Paragraph IV risk centered on obviousness, anticipation, written description, enablement, claim construction, and formulation design-around.
• Current US teriparatide entry risk is primarily regulatory, manufacturing, device-related, and commercial.
• Abaloparatide is outside the patent's literal human PTH (1-34) active-ingredient limitation.
• Foreign family members require separate jurisdiction-by-jurisdiction review.

FAQs About US Patent 7,144,861

Does US Patent 7,144,861 cover all Forteo products?

No. It covers products meeting the claimed formulation, concentration, sterility, buffering, preservative, stabilizer, and ready-to-use limitations. Other Forteo-related patents, device rights, or manufacturing rights may have covered different aspects.

Can a teriparatide product avoid this patent by using benzyl alcohol?

Potentially. Benzyl alcohol is expressly included in several claims, so substitution alone may not avoid infringement. The product would also need to avoid the applicable concentration, buffer, stabilizer, and presentation limitations.

Does a lyophilized teriparatide product infringe claim 1?

Usually not literally if the commercial product is a dry powder requiring reconstitution, because claim 1 requires an aqueous solution ready for parenteral administration. The complete specification, manufacturing process, and doctrine-of-equivalents issues would control a final analysis.

Is US Patent 7,144,861 a patent on the teriparatide sequence?

No. The patent claims pharmaceutical compositions, methods of preparing them, and a sealed vial. It does not claim the human PTH (1-34) sequence as such.

What is the main design-around strategy?

The clearest design-around options are changing the buffer, preservative, stabilizer, concentration, or dosage-form presentation while avoiding simultaneous satisfaction of every limitation in an asserted claim.

References

1. U.S. Food and Drug Administration. (2024). Forteo (teriparatide injection) prescribing information. FDA.
2. United States Patent and Trademark Office. (2006). U.S. Patent No. 7,144,861, Stable parathyroid hormone formulations. USPTO.
3. Google Patents. (n.d.). US7144861B2, Stable parathyroid hormone formulations. Google.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
5. U.S. Food and Drug Administration. (2023). Abbreviated new drug application approvals and patent certifications. FDA.
6. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drug products. FDA.

Drugs Protected by US Patent 7,144,861

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 7,144,861

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	018526
Austria	260113
Australia	1717799
Australia	759726
Brazil	9813463