Details for Patent: 11,255,842

« Back to Dashboard

Which drugs does patent 11,255,842 protect, and when does it expire?

Patent 11,255,842 protects TYMLOS and is included in one NDA.

This patent has fourteen patent family members in twelve countries.

Summary for Patent: 11,255,842

Title:	Methods for detecting neutralizing antibodies to parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP) analog
Abstract:	The present disclosure is directed to methods (e.g., in vitro methods) for detecting the presence of neutralizing antibodies to PTH or PTHrP analog in a sample. The in vitro method comprises the steps of obtaining a sample from a subject; contacting the sample with a cell; measuring cyclic adenosine monophosphate (cAMP) levels; and detecting the presence of neutralizing antibodies when cAMP levels are reduced relative to a negative control sample without neutralizing antibodies. An in vitro method of detecting the presence of neutralizing antibodies in a sample from a subject treated with Abaloparatide, is also provided. Further provided herein is a kit for carrying out the methods described herein comprising components required to carry out the obtaining, contacting, measuring and detecting steps and instructions for use.
Inventor(s):	Heidi K. Chandler
Assignee:	Radius Health Inc
Application Number:	US17/369,163
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,255,842
Patent Claim Types: see list of patent claims	Use; Device;

United States Patent 11,255,842: Abaloparatide Neutralizing-Antibody Assay Scope and Patent Landscape

U.S. Patent No. 11,255,842 protects a cell-based assay for detecting neutralizing antibodies generated against abaloparatide, the active ingredient in Tymlos. The independent claims cover: obtaining a treated subject’s sample, exposing abaloparatide-responsive cells to that sample, measuring cAMP signaling, and identifying neutralizing antibodies through reduced cAMP levels. Dependent claims narrow the method to UMR-106 cells, serum-starvation, PDE inhibition, abaloparatide preincubation, electrochemiluminescence, and defined assay concentrations. The patent also covers a kit and treatment-adjustment decisions based on the assay result. [1]

The patent is technically important as a biomarker and immunogenicity-testing patent, but it does not claim abaloparatide itself, Tymlos, a peptide composition, or a conventional pharmaceutical formulation. Its primary commercial risk is directed to laboratories, sponsors, contract research organizations, and diagnostic-kit suppliers that use the claimed functional assay.

What does U.S. Patent 11,255,842 claim?

Independent method claim

Claim 1 requires all of the following elements:

Claim element	Scope
Subject sample	A sample obtained from a subject treated with abaloparatide
Biological system	A cell or population of cells containing an abaloparatide receptor
Exposure step	Contacting the sample with the cells
Readout	Measuring intracellular cAMP
Detection principle	Reduced cAMP indicates neutralizing antibodies

The claim is functional rather than limited entirely to one cell line or one instrument. A laboratory may fall within claim 1 even if it uses a different receptor-bearing cell type, provided the cell system responds to abaloparatide and the assay uses cAMP reduction to identify neutralization.

The claim does not expressly require:

• UMR-106 cells;
• human serum;
• a competitive immunoassay;
• an electrochemiluminescent platform;
• a phosphodiesterase inhibitor;
• preincubation with abaloparatide;
• a particular abaloparatide concentration; or
• a kit.

Those features appear in dependent claims.

Functional mechanism

Abaloparatide activates the parathyroid hormone 1 receptor, or PTH1R, which stimulates cAMP signaling. Neutralizing antibodies can reduce effective abaloparatide activity. The assay therefore measures a biological consequence of antibody neutralization rather than merely detecting antibody binding.

A binding-antibody assay that identifies antibodies against abaloparatide without measuring functional inhibition would generally not satisfy the complete limitations of claim 1. Conversely, a cell-based neutralizing-antibody assay that uses a different quantitative cAMP readout may present a closer infringement question.

What do the dependent claims add?

Competitive immunoassay and electrochemiluminescence

Claims 2 and 3 narrow the cAMP measurement to a competitive immunoassay and, in claim 3, an electrochemiluminescent detection method. These limitations materially reduce the scope compared with claim 1.

A laboratory using a noncompetitive assay, luminescence, fluorescence, radiometric detection, or a different cAMP platform may avoid claims 2 and 3. It could still implicate claim 1 if the broader method limitations are met.

Serum incubation and abaloparatide preincubation

Claim 4 requires incubation of the cells with serum. Claims 5 and 6 require preincubation of the serum sample with a predetermined amount of abaloparatide PH for at least 30 minutes.

These claims target a competition format in which circulating neutralizing antibodies are exposed to a defined amount of abaloparatide before cell contact. The preincubation step can improve assay standardization by ensuring that the antibody challenge is measured against a known drug concentration.

Claims 11 and 12 further specify abaloparatide concentrations ranging from at least 100 pg/mL through at least 500 pg/mL, with approximately 600 pg/mL expressly identified.

PDE inhibition

Claims 8 and 9 require prior incubation with a cell-permeable cAMP-specific phosphodiesterase inhibitor. Claim 9 identifies 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone, commonly associated with the PDE4 inhibitor rolipram.

This limitation is directed to signal preservation. By inhibiting cAMP degradation, the assay can increase the detectable difference between active abaloparatide signaling and neutralization by patient antibodies.

A competing assay that does not use a PDE inhibitor may avoid claims 8 and 9 while remaining exposed to broader claim 1.

UMR-106 cells and serum starvation

Claim 13 specifies the rat osteoblast-like epithelial cell line UMR-106. Claim 14 adds serum starvation. Claim 15 defines starvation periods ranging from approximately four to 48 hours, including preferred ranges of six to 12 hours.

These claims provide narrower, protocol-level protection. They are easier to design around than claim 1 because a developer could use another PTH1R-expressing cell line, a recombinant cell system, primary cells, or a cell-free signaling platform, subject to the remaining claim limitations.

Human serum and treatment decisions

Claims 16 and 17 narrow the sample to a human sample and human serum. Claims 18 and 20 extend the claimed method into clinical management:

• discontinuing abaloparatide treatment when neutralizing antibodies are detected; or
• increasing or decreasing the abaloparatide dose when neutralizing antibodies are detected.

These claims may create additional infringement exposure for a sponsor or clinical laboratory if the assay is tied to treatment decisions. They also raise claim-construction issues because the claims combine laboratory testing with a downstream clinical action.

How strong is the patent estate for abaloparatide neutralizing-antibody testing?

The estate represented by Patent 11,255,842 is strongest against a specific functional assay architecture:

1. patient serum from an abaloparatide-treated subject;
2. abaloparatide-responsive cells;
3. cAMP as the biological readout;
4. reduced cAMP as the neutralization signal;
5. optional preincubation with abaloparatide;
6. optional PDE inhibition; and
7. a defined UMR-106 or electrochemiluminescent implementation.

The broadest practical risk comes from claim 1. Its cell and receptor language is not limited to UMR-106 cells, the Multi-Array platform, or one concentration of abaloparatide.

The estate is weaker against:

• anti-drug antibody binding assays;
• assays measuring antibody titer without functional neutralization;
• assays using a non-cAMP signaling endpoint;
• assays using a cell-free receptor-binding system;
• assays that measure calcium, reporter-gene activity, or another downstream pathway;
• assays using a different drug challenge format; and
• clinical decisions based on an independently generated laboratory result.

The central validity issues would likely involve written description, enablement, anticipation, and obviousness. The specification would need to support the breadth of “a receptor for abaloparatide” and the use of different receptor-bearing cells. Prior-art searches would focus on PTH1R functional bioassays, cAMP-based neutralizing-antibody assays, immunogenicity testing for peptide therapeutics, and prior use of UMR-106 cells.

What is the patent expiration date?

Patent 11,255,842 issued on April 26, 2022. A U.S. utility patent generally runs for 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, and other statutory adjustments. [1][4]

The exact expiration date cannot be established from the claim text alone. The critical date is the effective nonprovisional or international filing date shown in the USPTO patent record, not the grant date. The patent is not a short-term regulatory-exclusivity right. Its enforceable term depends on the recorded USPTO term calculation.

The patent’s subject matter also differs from FDA exclusivity for Tymlos. FDA regulatory exclusivity and patent protection are separate rights. A product may lose FDA exclusivity while remaining covered by a patent, or retain patent protection that does not prevent an otherwise approvable application from being filed.

What is the Orange Book status of Patent 11,255,842?

Patent 11,255,842 is a diagnostic method patent and would not ordinarily qualify as an Orange Book-listed patent for an abaloparatide drug product. The Orange Book lists patents submitted by a new drug application holder that claim the approved drug substance, drug product, or an approved method of use. [2][3]

The claims here are directed to detecting neutralizing antibodies and making treatment decisions. They do not claim:

• abaloparatide as a chemical composition;
• the Tymlos pen;
• a pharmaceutical formulation;
• a dosage regimen for osteoporosis independent of antibody testing; or
• a manufacturing process for abaloparatide.

Accordingly, the patent should be treated as a separate diagnostic and clinical-testing right rather than as a conventional Orange Book barrier to an abaloparatide ANDA.

Are Paragraph IV challenges relevant?

A Paragraph IV certification is ordinarily used when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. [2] Because Patent 11,255,842 is not, based on its claim type, a conventional product or method-of-use patent for the approved abaloparatide product, it is not the principal patent that would determine generic entry for Tymlos.

A generic applicant could market an abaloparatide product without practicing the claimed diagnostic method. Manufacturing and selling abaloparatide does not, by itself, satisfy the steps of obtaining a treated subject’s serum, contacting receptor-bearing cells, measuring cAMP, and detecting reduced signaling.

A Paragraph IV dispute could arise if the patent were listed or asserted against an ANDA applicant’s proposed labeling or testing activities, but the supplied claim set does not create an automatic product-level barrier.

What generic entry risks exist?

Drug-product entry

The patent presents limited direct risk to a generic abaloparatide manufacturer. A generic applicant can seek approval for the drug product without using the claimed neutralizing-antibody assay.

The principal barriers to generic entry would instead involve:

• composition-of-matter patents;
• formulation patents;
• device patents;
• manufacturing-process patents;
• method-of-use patents;
• regulatory exclusivity; and
• any patent litigation involving the commercial product.

Patent 11,255,842 does not by itself prevent an ANDA applicant from making, importing, or selling abaloparatide.

Diagnostic and clinical-trial use

The risk is higher for:

• a sponsor conducting immunogenicity studies;
• a CRO running a neutralizing-antibody assay;
• a diagnostic company selling an assay kit;
• a laboratory using UMR-106 cells and cAMP measurement; or
• a healthcare system using the assay to alter treatment.

Claim 19 is directed to a kit containing components and instructions for performing the claimed method. A kit supplier could face exposure even if the purchaser performs the assay.

Which companies are likely to face competitive exposure?

The relevant competitive field includes four groups:

Group	Potential activity	Exposure under Patent 11,255,842
Abaloparatide sponsor or licensee	Clinical immunogenicity testing and postmarketing monitoring	Potentially high if the claimed assay is used
CROs	Assay development and validation	Potentially high if they perform the method for clients
Diagnostic companies	Kits and assay platforms	High for claim 19 and method claims
Generic manufacturers	Product development and ANDA filing	Low unless they use or promote the claimed assay

The claims do not directly target competing anabolic osteoporosis drugs such as teriparatide or romosozumab unless an assay uses abaloparatide and satisfies the claim limitations. A neutralizing-antibody assay for another drug would generally fall outside the literal scope.

What design-around strategies are available?

Potential design-around approaches include:

1. Use a binding-antibody assay without a functional cAMP endpoint.
2. Measure a different intracellular signaling marker.
3. Use a cell-free receptor-binding assay.
4. Use a different biological pathway or reporter system.
5. Avoid the claimed abaloparatide preincubation protocol.
6. Avoid the specified PDE inhibitor.
7. Use a non-UMR-106 cell system where the broader claim is not otherwise met.
8. Separate laboratory testing from dose-adjustment instructions.
9. Use a different kit architecture and independently developed instructions.

Design-around analysis must assess claim 1 first. Avoiding dependent-claim features does not avoid infringement if the alternative still satisfies every limitation of claim 1.

What litigation and licensing issues affect the patent?

The supplied record identifies no settlement, license, or litigation terms. The patent’s commercial value would most likely arise through:

• a license to the abaloparatide sponsor;
• a CRO testing agreement;
• a diagnostic-platform license;
• a covenant not to sue for clinical-trial use; or
• an assay-validation collaboration.

A license would be particularly relevant if the patent owner controls the validated immunogenicity assay used in clinical development or regulatory submissions. Patent ownership alone does not establish that the patent owner controls all neutralizing-antibody testing methods.

The main litigation questions would be whether an accused assay uses a cAMP-based functional neutralization readout and whether the accused cells contain a receptor capable of responding to abaloparatide. Expert testimony would likely address assay operation, receptor biology, signal inhibition, and whether reduced cAMP is caused by neutralizing antibodies rather than nonspecific serum effects.

How does this patent compare with abaloparatide product patents?

Patent 11,255,842 is an ancillary patent with a different economic function from a composition or formulation patent.

Patent category	Typical protected subject matter	Effect on generic entry
Composition patent	Abaloparatide molecule or peptide analog	Direct product barrier
Formulation patent	Vehicle, concentration, stability, delivery system	May require formulation design-around
Device patent	Injection pen or delivery mechanism	May affect device substitution
Method-of-use patent	Osteoporosis treatment regimen	Label and carve-out issues
Diagnostic patent	Neutralizing-antibody assay	Primarily affects testing and monitoring
Manufacturing patent	Peptide synthesis or purification	May affect process selection

The ’842 patent is narrow in commercial target but potentially valuable in a regulated clinical-development setting because validated immunogenicity assays can become embedded in trial protocols, pharmacovigilance programs, and regulatory submissions.

Key Takeaways

• U.S. Patent 11,255,842 covers a functional cell-based assay for neutralizing antibodies to abaloparatide.
• Claim 1 is the principal risk because it is not limited to UMR-106 cells, one instrument, or one cAMP assay format.
• Dependent claims protect specific implementations using competitive immunoassay, electrochemiluminescence, abaloparatide preincubation, rolipram, UMR-106 cells, and serum starvation.
• Claim 19 covers a kit for carrying out the assay.
• Claims 18 and 20 extend the method into treatment discontinuation and dose adjustment.
• The patent does not claim abaloparatide, Tymlos, a drug formulation, or a manufacturing process.
• It is not the principal patent barrier to generic abaloparatide entry and is not the type of patent ordinarily associated with Orange Book product listings.
• The highest infringement risk is for assay developers, CROs, diagnostic-kit suppliers, and sponsors using the claimed cAMP-based method.
• The exact patent expiration date depends on the effective filing date, patent-term adjustment, and any terminal disclaimer recorded by the USPTO.

FAQs

Can a generic company sell abaloparatide without infringing Patent 11,255,842?

Yes, product sale alone does not practice the claimed diagnostic steps. Risk increases if the company uses or supplies the claimed assay.

Does a neutralizing-antibody binding assay infringe this patent?

Not necessarily. The claims require a functional assay involving abaloparatide-responsive cells and cAMP measurement, not merely antibody binding.

Is UMR-106 required for every claim?

No. UMR-106 appears in dependent claims 13 through 15. Claim 1 covers a broader class of cells containing a receptor for abaloparatide.

Does claim 19 cover a general abaloparatide test kit?

No. The kit must include components required to perform the method of claim 1 and instructions for use. A kit using a different assay principle may fall outside the claim.

Can a company avoid the patent by measuring calcium instead of cAMP?

That may avoid the express cAMP limitation, provided the alternative assay does not otherwise satisfy the claim through an equivalent process. The infringement analysis would depend on the exact assay design and claim interpretation.

References

1. United States Patent and Trademark Office. (2022). U.S. Patent No. 11,255,842: Methods for detecting neutralizing antibodies to abaloparatide.
2. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2023). Approved drug product list, Orange Book.
4. United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance.

Drugs Protected by US Patent 11,255,842

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Radius	TYMLOS	abaloparatide	SOLUTION;SUBCUTANEOUS	208743-001	Apr 28, 2017		RX	Yes	Yes	11,255,842					USE FOR DETECTING NEUTRALIZING ANTIBODIES

International Family Members for US Patent 11,255,842

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020207653
Brazil	112021011566
Canada	3122231
China	113286818
Colombia	2021007715
European Patent Office	3908605