Details for Patent: 11,680,942

Which drugs does patent 11,680,942 protect, and when does it expire?

Patent 11,680,942 protects TYMLOS and is included in one NDA.

This patent has fourteen patent family members in twelve countries.

Summary for Patent: 11,680,942

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:	US17/571,312
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,680,942
Patent Claim Types: see list of patent claims	Use; Device;

United States Patent 11,680,942: Claim Scope, Abaloparatide Neutralizing-Antibody Assay, and Patent Landscape

U.S. Patent No. 11,680,942 protects a cell-based bioassay for detecting neutralizing antibodies against abaloparatide in serum. The core claim requires preincubation of serum with abaloparatide, exposure to rat UMR-106 cells, measurement of cAMP through a competitive electrochemiluminescent immunoassay, and identification of neutralizing antibodies from reduced cAMP activity. The patent is directed to immunogenicity testing and assay kits, not to abaloparatide composition, formulation, treatment, or generic drug manufacture.

The principal infringement risk is concentrated in assays that reproduce the full combination of UMR-106 cells, abaloparatide preincubation, cAMP measurement, and electrochemiluminescent detection.

What does U.S. Patent 11,680,942 protect?

The patent protects an in vitro method and a related kit for detecting functional, or neutralizing, antibodies to abaloparatide. Unlike a binding-antibody assay, the claimed method measures whether antibodies interfere with abaloparatide's biological activity.

Abaloparatide activates the parathyroid hormone 1 receptor, or PTH1R, on responsive cells. PTH1R activation stimulates adenylate cyclase and increases intracellular cAMP. Neutralizing antibodies reduce this signal by preventing abaloparatide from activating the receptor.

The patent's independent method claim requires all of the following elements:

Required element	Claim requirement
Sample	Serum from a subject treated with abaloparatide
Preincubation	Serum is preincubated with a predetermined amount of abaloparatide
Preincubation time	At least 30 minutes
Cell system	Rat epithelial UMR-106 cell or cell population
Cell exposure	Preincubated serum is contacted with the cells and incubated
Readout	cAMP measurement
Detection platform	Competitive immunoassay using electrochemiluminescent detection
Positive interpretation	Reduced cAMP compared with a negative control lacking neutralizing antibodies

Each limitation matters. A test using a different cell line, a different detection technology, or a nonfunctional antibody-binding endpoint would not literally satisfy the complete method claim.

How broad is independent claim 1?

Claim 1 is technically specific but commercially meaningful. It is narrower than a general claim to detecting anti-abaloparatide antibodies because it requires a defined biological assay architecture.

The claim does not appear limited to a particular:

• Patient disease;
• Dose of abaloparatide administered;
• Serum volume;
• Specific type of neutralizing antibody;
• Commercial instrument used for electrochemiluminescence;
• Particular cAMP antibody or calibration reagent;
• Exact incubation temperature, except where dependent claims add conditions.

The claim does require UMR-106 cells. This is a major narrowing limitation. A competitor using osteoblast-like cells, HEK293 cells engineered to express PTH1R, CHO cells, or another receptor-bearing cell line would have a noninfringement position based on the express cell limitation, subject to doctrine-of-equivalents analysis.

The claim also requires electrochemiluminescent detection. A competitor using ELISA, time-resolved fluorescence, luminescence, mass spectrometry, radiometric detection, or a direct fluorescent assay would not literally meet that limitation.

What do dependent claims 2 through 10 add?

The dependent claims define operating parameters that narrow the patented assay and provide potential fallback positions during validity or infringement disputes.

Claim	Added limitation	Commercial significance
2	Approximately 40 µL of cells at approximately 10^6 cells/mL; room temperature; 1 to 2 hours	Captures a defined assay format and cell-loading condition
3	Abaloparatide concentration of 100 to 500 pg/mL	Covers a low-concentration assay window
4	Abaloparatide concentration of 600 pg/mL	Protects a specific assay concentration
5	Cell lysis before cAMP measurement	Ties the readout to intracellular cAMP recovery
6	Lysis buffer at room temperature for approximately 5 to 30 minutes	Narrows the lysis procedure
7	Cell-permeable cAMP-specific phosphodiesterase inhibitor	Stabilizes intracellular cAMP and improves signal
8	4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone	Identifies a specific PDE inhibitor, commonly known as rolipram
9	Serum starvation for 4 to 48 hours	Reduces basal signaling and improves assay sensitivity
10	Serum starvation subranges from 4 to 24, 4 to 16, 4 to 12, or 6 to 12 hours	Creates narrower dependent-claim positions
11	Serum from a human subject	Limits the source to human clinical samples

Claims 3 and 4 create separate concentration positions. A method using 600 pg/mL may satisfy claim 4 even though it falls outside the express 100 to 500 pg/mL range in claim 3.

Claim 8 is especially narrow. Use of a different phosphodiesterase inhibitor could avoid claim 8, although it would remain relevant to claim 7 if the inhibitor is cell permeable and cAMP-specific.

What does claim 12 protect?

Claim 12 protects a kit for carrying out the claim 1 method. The kit must include components required for obtaining, preincubating, contacting, measuring, and detecting, together with instructions for use.

The kit claim raises two practical issues.

First, a kit must be configured for the claimed assay rather than merely being a generic research kit. Components that support the required UMR-106-cell assay, abaloparatide preincubation, cAMP measurement, and electrochemiluminescent detection create greater exposure.

Second, kit infringement may be assessed separately from performance of the assay. Sale of a complete kit with instructions directing users to perform the patented method can create inducement or contributory-infringement issues even when the seller does not perform the assay itself.

What technical steps are required to practice the patented assay?

A practical workflow based on the claims is:

1. Obtain serum from an abaloparatide-treated subject.
2. Add abaloparatide to the serum.
3. Preincubate the mixture for at least 30 minutes.
4. Add the mixture to UMR-106 cells.
5. Incubate the cells with the mixture.
6. Lyse the cells if the assay follows claims 5 and 6.
7. Measure cAMP with a competitive immunoassay using electrochemiluminescence.
8. Compare the result with a negative control.
9. Identify neutralizing antibodies when cAMP is reduced relative to the control.

The assay is a functional neutralization assay. It does not merely determine whether antibodies bind abaloparatide. The biological endpoint is loss of receptor-mediated cAMP signaling.

How does the patent differ from a binding-antibody assay?

A binding-antibody assay generally measures antibody recognition of abaloparatide using labeled drug or an immobilized antigen. It can detect antibodies that bind the peptide even if they do not block receptor activation.

Patent 11,680,942 requires a functional cellular response. This distinction affects both scientific utility and infringement analysis.

Attribute	Patent 11,680,942	Binding-antibody assay
Biological endpoint	Reduced cAMP signaling	Antibody-drug binding
Cell requirement	UMR-106 cells	Often no cells
Neutralization measured	Yes	Not necessarily
Detection method	Competitive ECL immunoassay	Variable
Receptor signaling	Required in practice	Not required
Typical use	Functional immunogenicity characterization	Screening and antibody incidence

A sponsor that uses a binding assay followed by a separate functional assay may need to evaluate the functional assay independently. The binding assay alone would not contain the full combination of claim 1.

What patent landscape surrounds abaloparatide?

The relevant patent landscape has four distinct layers.

Abaloparatide composition patents

These patents cover the peptide sequence, analogs, salts, chemical forms, or related PTH-related protein compounds. They are the most directly relevant to product exclusivity and generic entry.

Formulation and delivery patents

These patents may cover injectable formulations, excipients, concentration ranges, stability, prefilled pens, cartridges, or administration systems. A generic or 505(b)(2) applicant may need to address these patents separately from composition patents.

Method-of-treatment patents

These patents can cover osteoporosis treatment, dosing schedules, treatment duration, patient selection, sequential therapy, or fracture-risk populations. Their practical value depends on FDA labeling and the scope of the proposed generic label.

Immunogenicity and assay patents

Patent 11,680,942 falls into this category. It protects a testing method rather than the therapeutic product. Its commercial value is concentrated in clinical development, postmarketing surveillance, contract laboratory testing, and kit supply.

The assay patent therefore sits at the edge of the abaloparatide product estate. It does not, based on the provided claims, prevent a competitor from making abaloparatide, selling a formulation, or conducting osteoporosis treatment. It can affect how a company validates and commercializes a neutralizing-antibody test.

What is the FDA and Orange Book relevance?

Tymlos, the abaloparatide product marketed by Radius Health, received FDA approval for postmenopausal women with osteoporosis at high risk for fracture. The product is an injectable peptide drug administered subcutaneously.[2]

Patent 11,680,942 is unlikely to be the principal Orange Book patent for Tymlos because its claims cover an immunogenicity assay rather than the drug substance, drug product, formulation, delivery device, or method of use. Orange Book listing generally focuses on patents that claim the approved drug or an approved method of using it.[3]

The patent may still have regulatory relevance in:

• Clinical immunogenicity studies;
• Validation of neutralizing-antibody assays;
• Biologics and peptide-drug comparability packages;
• Postmarketing safety surveillance;
• Contract research organization testing;
• Analytical kit supply.

Abaloparatide is a chemically defined peptide drug, not a monoclonal antibody or other conventional biologic. A follow-on applicant would generally evaluate an ANDA or 505(b)(2) pathway rather than a biosimilar application. Biosimilar risk is therefore limited for this patent. The principal regulatory risk is assay-method freedom to operate, not biosimilar substitution.

When does U.S. Patent 11,680,942 expire?

A U.S. utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments.[4]

The grant date, June 27, 2023, does not determine the expiration date. The relevant term must be calculated from the patent's priority and application data in the USPTO record. A patent-term adjustment can extend the nominal term, while a terminal disclaimer can shorten it.

The assay patent's remaining term should be evaluated separately from any composition, formulation, or method-of-treatment patent covering Tymlos. Its expiration will not necessarily coincide with the expiration of the core abaloparatide product patents.

Which companies are most exposed to the patent?

The likely exposure is operational rather than product-launch exposure.

Company type	Exposure
Radius Health or successor product owner	Ownership, licensing, and enforcement of the assay estate
Contract research organizations	Performance of neutralizing-antibody assays
Generic or 505(b)(2) developers	Use of the assay in development or immunogenicity work
Diagnostic-kit suppliers	Sale of kits configured for the claimed method
Academic laboratories	Research use, depending on commercial purpose and jurisdiction
Competing peptide developers	Possible use of the platform for abaloparatide-specific testing

A company can avoid substantial risk by using a different cell line or a different detection platform. That design-around strategy may preserve the scientific objective while avoiding the express combination in claim 1.

What patent litigation or Paragraph IV challenges affect the patent?

The provided claims do not establish a Paragraph IV certification, infringement action, settlement, or license involving U.S. Patent 11,680,942. Paragraph IV challenges ordinarily arise in an ANDA applicant's certification against patents listed for the reference drug in the Orange Book. A diagnostic assay patent would not ordinarily be the central patent asserted against a generic abaloparatide product unless it is listed and relevant to an approved use or product claim.

The more likely dispute types are:

• Patent infringement involving a commercial neutralizing-antibody assay;
• Ownership or inventorship disputes;
• Validity challenges based on prior cell-based cAMP assays;
• Written-description or enablement challenges;
• Obviousness challenges based on known PTH1R signaling assays;
• Contract disputes involving licensed assay technology.

No settlement terms or active litigation status can be inferred from the claim text alone.

How strong is the patent estate for commercial enforcement?

The patent has meaningful specificity but a relatively narrow literal scope.

Strengths

• It claims a functional neutralizing-antibody assay rather than a generic antibody-binding test.
• It identifies UMR-106 cells.
• It specifies electrochemiluminescent cAMP detection.
• It includes operational fallback claims covering cell density, timing, concentration, lysis, PDE inhibition, and serum starvation.
• It includes a kit claim that may reach commercial assay packages.

Weaknesses

• The UMR-106 limitation creates a clear design-around route.
• The electrochemiluminescence limitation excludes many alternative readouts.
• Cell-based cAMP assays and PTH-related protein signaling assays may provide prior-art material for validity challenges.
• The claim language referring to measuring cAMP "in the serum sample" after cellular exposure may create claim-construction issues because cAMP is ordinarily measured intracellularly or in a cell lysate.
• The patent does not appear to claim the abaloparatide molecule itself, its formulation, its delivery device, or its therapeutic use.

The strongest enforcement scenario is a commercial laboratory or kit provider using substantially the claimed assay protocol. The weakest scenario is a developer using a different cell line and a non-ECL functional readout.

What generic entry risks exist?

The patent creates limited direct generic-entry risk. It does not, on the supplied claims, block manufacture or sale of abaloparatide.

Generic and 505(b)(2) developers should separate three issues:

1. Product patents covering abaloparatide or its formulation.
2. Method-of-use patents tied to the approved osteoporosis indication.
3. Analytical patents covering immunogenicity or neutralizing-antibody testing.

A generic applicant may use a noninfringing assay for development and regulatory support. If the applicant contracts with a laboratory that uses the patented assay, the commercial testing arrangement may require a license or a design-around.

What licensing and freedom-to-operate issues matter?

A license review should examine:

• Ownership of the patent and continuation applications;
• Any rights retained by inventors, research institutions, or technology suppliers;
• Rights to UMR-106 cells and related materials;
• Rights to electrochemiluminescent assay reagents and instruments;
• Use restrictions imposed by reagent or instrument licenses;
• Continuation, divisional, or foreign-family applications;
• Assignments recorded after issuance;
• Any covenant not to sue or settlement agreement.

The patent number alone does not establish whether the patent is exclusively licensed, nonexclusively licensed, or held by the original assignee.

Key Takeaways

• U.S. Patent 11,680,942 covers a functional assay for abaloparatide neutralizing antibodies.
• Claim 1 requires serum preincubation with abaloparatide for at least 30 minutes, UMR-106 cells, cAMP measurement, competitive ECL detection, and reduced cAMP relative to a negative control.
• Claims 2 through 10 add specific cell, concentration, lysis, PDE-inhibitor, and serum-starvation conditions.
• Claim 12 covers a kit configured to perform the claimed assay.
• The patent does not claim abaloparatide composition, formulation, delivery, or osteoporosis treatment based on the supplied claims.
• A different cell line or non-ECL readout is the clearest design-around path.
• The patent is more relevant to CROs, diagnostic-kit suppliers, and clinical assay laboratories than to ordinary generic drug manufacturing.
• It is unlikely to be the principal Orange Book barrier to abaloparatide generic entry.
• Expiration requires review of the patent's earliest effective nonprovisional filing date, patent-term adjustment, and any terminal disclaimer.
• No Paragraph IV challenge, litigation outcome, or settlement can be established from the claim text.

FAQs About U.S. Patent 11,680,942

Does the patent cover all tests for anti-abaloparatide antibodies?

No. It covers a defined cell-based functional assay. A binding-antibody assay or a neutralization assay using a different cell line may fall outside the literal scope of claim 1.

Can a laboratory avoid the patent by using HEK293 cells?

Potentially. Claim 1 expressly requires rat epithelial UMR-106 cells. A HEK293 assay would not literally satisfy that limitation, although the full legal analysis would include equivalents and other claims.

Is abaloparatide a biologic for biosimilar purposes?

Abaloparatide is a synthetic peptide drug regulated under an NDA pathway. A follow-on product would generally be assessed under ANDA or 505(b)(2) procedures rather than the conventional biosimilar pathway.

Does the patent block a generic Tymlos manufacturer?

Not directly based on the supplied claims. The patent targets neutralizing-antibody testing, while generic entry is principally controlled by product, formulation, device, and method-of-use patents.

What is the most important claim limitation for freedom-to-operate?

The combination of UMR-106 cells and competitive electrochemiluminescent cAMP detection is the most important practical limitation. Removing either element may provide a noninfringement strategy, subject to the doctrine of equivalents and any related continuation patents.

References

1. United States Patent and Trademark Office. (2023). U.S. Patent No. 11,680,942: Methods for detecting neutralizing antibodies to abaloparatide.

2. U.S. Food and Drug Administration. (2023). Tymlos (abaloparatide) prescribing information. Radius Health, Inc.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.

4. United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.

Drugs Protected by US Patent 11,680,942

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	11,680,942					USE FOR DETECTING NEUTRALIZING ANTIBODIES

International Family Members for US Patent 11,680,942

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
Israel	284533