United States Patent 9,480,742: Claim-Scoped Antibody Method Claims Targeting Anti-ActRIIa Signaling

US Patent 9,480,742 contains a claim set centered on administering an anti-ActRIIa antibody to promote bone formation and/or improve bone parameters by antagonizing an activin-ActRIIa signaling pathway. The independent claim structure is method-of-treatment oriented, with dependent claims narrowing to antibody format (monoclonal; humanized/fully human) and to combination therapy with established bone-active agents. Dependent claims expand the clinical perimeter to osteoporosis subtypes and cancer-associated bone loss and bone pathology (bone metastases, multiple myeloma, Paget’s disease).

This landscape analysis treats the claims as enforceable technology around (i) the biologic target and mechanism (ActRIIa antagonism), (ii) the therapeutic modality (anti-ActRIIa antibodies), and (iii) the method framing (bone growth, density, strength; bone-disorder contexts). The key questions for freedom-to-operate and valuation are: which parts are already crowded by prior art; which limitations meaningfully narrow claim scope; and whether downstream “design-around” options exist that avoid literal claim coverage while still achieving clinical results.

What exactly do the claims cover, in enforceable terms?

Core independent claim scope (Claim 1 and Claim 9)

Claim 1 is a method claim with three technical pillars:

Administration element: administering to a subject an “effective amount” of an anti-ActRIIa antibody.
Functional mechanism: the antibody antagonizes an activin-ActRIIa signaling pathway.
Outcome frame: the method is for “promoting bone growth, increasing bone density, or increasing bone strength.”

Claim 9 is a complementary method claim framed as treatment of a bone-related disorder associated with low bone density or decreased bone strength, again using the same therapeutic construct: an anti-ActRIIa antibody antagonizing an activin-ActRIIa signaling pathway.

Practical effect: the claims are drafted to capture any anti-ActRIIa antibody that functionally antagonizes activin-ActRIIa signaling when used for bone outcomes, including in specific disorder contexts in dependent claims.

Key dependent claim narrowing (Claims 2-3, 10-11)

Claim 2 / Claim 10: specifies monoclonal antibody.
Claim 3 / Claim 11: specifies humanized or fully human antibody.

Practical effect: these dependent claims create layered coverage, but they are not substitutes for Claim 1 and Claim 9. They add fallback positions that can matter if prior art attacks the broader “anti-ActRIIa antibody” phrasing.

Combination therapy perimeter (Claims 7-8, 12-13)

Claim 7 / Claim 12: adds a second bone-active agent.
Claim 8 / Claim 13: restricts the second agent to a defined list:
- bisphosphonate
- estrogen
- selective estrogen-receptor modulator
- parathyroid hormone
- calcitonin
- calcium supplement
- vitamin D supplement

Practical effect: if a competitor runs an anti-ActRIIa antibody program as monotherapy, these dependent claims are not directly invoked. If the competitor uses one of these listed agents in combination, these dependents create sharper infringement hooks.

Disorder-specific claims (Claims 14-23)

Claim 9 is broadened by dependents to cover specific indications:

Osteoporosis subtypes:
- Claim 14: primary osteoporosis
- Claim 15: post-menopausal osteoporosis
- Claim 16: secondary osteoporosis
- Claim 17: hypogonadal bone loss
Cancer-associated bone loss / bone disease:
- Claim 18: cancer associated with bone loss
- Claim 19: recipient of cancer treatment regimen associated with bone loss
- Claim 20: bone metastases
- Claim 21: multiple myeloma
- Claim 23: cancer associated with bone metastases
Other bone disorder:
- Claim 22: Paget’s disease

Practical effect: this set aims to prevent a competitor from limiting infringement exposure by selecting an alternative bone indication within the osteoporosis and oncology-bone space.

What is the claim “center of gravity” that matters for prior art and design-around?

1) Target and mechanism limitation: “anti-ActRIIa antibody” antagonizing “activin-ActRIIa signaling”

The most important constraint is not the clinical endpoint. It is the requirement that the administered biologic is an anti-ActRIIa antibody and that it functionally antagonizes activin-ActRIIa signaling.

That is a common vulnerability in litigation: prior art often discloses ActRIIa-pathway modulation for bone disorders. If earlier documents disclose antibodies (or antibody-like biologics) that inhibit ActRIIa ligands/signaling to increase bone mass, the novelty may collapse unless the patent claims a specific antibody class, epitope, sequence, binding kinetics, or assay-defined antagonist behavior.

2) Modality type: antibody format

The independent claims do not require monoclonality or humanization. Those are introduced via dependents. If the patent owner’s commercial product is a humanized or fully human monoclonal, dependents become valuable in post-prior-art narrowing. But enforceable breadth in Claim 1/9 still reads on non-humanized monoclonals and potentially non-monoclonal anti-ActRIIa antibody formats, depending on claim construction and prosecution history.

3) Combination-agent list

The enumerated combination agents are a strong drafting signal. This list can also be used defensively by accused infringers to argue “no listed second bone-active agent” when the combination differs.

4) Indication breadth

The indication language is broad enough to cover most osteoporosis and oncology-bone applications. That breadth increases infringement surface area but also heightens prior-art risk because osteoporosis and bone-metastasis bone loss are heavily studied.

How strong is the claim set versus typical novelty/obviousness pressure points?

Novelty risk: “anti-ActRIIa antibody for bone” is likely already known

A rational reading of the claim set suggests the invention is not the mere use of an ActRIIa antagonistic pathway approach. The novelty would have to rest on one or more of the following:

a specific class of anti-ActRIIa antibodies,
a specific mechanistic interpretation tied to “activin-ActRIIa” vs broader ActRII family signaling,
or specific clinical effect framing and/or dosing strategy.

Absent such details (the claims provided do not include sequence/epitope/dose/assay thresholds), novelty may depend on the patent’s specification and how it defines “anti-ActRIIa antibody” and “antagonizes” in functional terms.

Obviousness risk: ActRIIa-targeted biology is a known translational axis

If earlier disclosures teach bone mass improvement via inhibition of ActRIIa signaling, then claiming a method that administers an anti-ActRIIa antibody to improve bone density/strength is the kind of predictable “molecular-to-clinic” adaptation that can trigger obviousness arguments. Dependents specifying humanized/fully human monoclonals can reduce this risk only if prior art lacks that exact modality or functional performance.

Indication-specific dependents may not save non-novel core method claims

Claims 14-23 likely face a standard argument: even if specific subtypes (e.g., hypogonadal bone loss, Paget’s disease, multiple myeloma) were not individually tested with the claimed antibody, the broader method already predicts bone outcomes if the mechanism is established. That makes the core limitation (anti-ActRIIa antibody antagonizing activin-ActRIIa signaling) the primary battleground.

Where is the landscape most crowded: mechanism-first versus antibody-first?

Mechanism-first crowding

The language “activin-ActRIIa signaling” implies a focus on the activin axis engaging ActRIIa receptors. If the prior art includes inhibition of this axis (or ActRIIa broadly) for bone remodeling, then the landscape is crowded at the mechanism level.

Antibody-first crowding

Even if the prior art uses ligand traps, soluble receptors, peptides, or non-antibody biologics, Claim 1/9 are specific to antibodies. So crowding depends on whether earlier documents also disclose antibody formats targeting ActRIIa and using functional antagonism language tied to activin signaling.

Combination crowding

Combination use with osteoporosis standard-of-care (bisphosphonates, estrogen/SERM, PTH, calcitonin, calcium, vitamin D) is common. If earlier documents combine bone agents with an ActRIIa pathway antagonist, then Claims 7-8 and 12-13 face added vulnerability.

What would likely be the strongest design-around levers for a competitor?

1) Avoid “anti-ActRIIa antibody”

A competitor can aim for:

biologics that target a different receptor (e.g., related signaling components) without being anti-ActRIIa, or
strategies that use non-antibody modalities.

If their mechanism still affects bone outcomes, they may still be clinically competitive, but they reduce direct literal infringement risk if “anti-ActRIIa antibody” is strictly construed.

2) Avoid “antagonizes activin-ActRIIa signaling”

If a competitor’s candidate blocks ActRIIa-mediated signaling but not specifically via the activin-ActRIIa pathway, the mechanism limitation may become a litigation focal point. Claim language is functional, so assay definitions matter.

3) Avoid listed combination agents

If the competitor uses a combination that omits the enumerated second bone-active agent list, the dependents that require that exact set are harder to reach.

4) Use non-covered indications

The claims cover a wide set of bone outcomes and disorders, especially osteoporosis and oncology-bone disease. A narrow, non-overlapping indication could reduce infringement risk, but given the claim breadth, this is less reliable than mechanism or modality design-around.

Claim-by-claim infringement surface: what typically triggers exposure

Most direct triggers (claims 1 and 9)

Any regimen where an anti-ActRIIa antibody is administered to patients for:
- increased bone density,
- increased bone strength, or
- promoting bone growth.

Additional triggers

If the anti-ActRIIa antibody is explicitly monoclonal and/or humanized/fully human, Claims 2-3 and 10-11 are more accessible as fallback positions.
If the regimen includes one of the listed agents, Claims 7-8 and 12-13 expand exposure.
If development includes any of the enumerated indications (primary/post-menopausal/secondary osteoporosis; hypogonadal bone loss; Paget’s; multiple myeloma; bone metastases), Claims 14-23 become directly relevant.

What does the patent landscape likely look like around this technology?

Even without the full citation list here, the claim drafting points to a landscape where multiple players converge on:

ActRIIa inhibition for bone mass gains,
antibody or antibody-like biologics that neutralize ActRIIa pathway signaling,
osteoporosis and cancer-bone indications,
and combination regimens with standard osteoporosis drugs.

From an investor or R&D portfolio lens, that implies high competition at the mechanism level. In such settings, patents usually succeed when they are drafted with:

antibody-specific attributes (sequence, epitope),
assay-defined functional thresholds,
dosing regimen specifics,
or method distinctions that are not obvious from mechanism alone.

The claims as provided are mechanism-and-modality broad, suggesting that the value hinges on how the specification and prosecution history define and distinguish “anti-ActRIIa antibody” and “antagonizes activin-ActRIIa signaling,” and on whether earlier documents disclose the same antibody class and functional effects.

Key Takeaways

Claims 1 and 9 are the core: any anti-ActRIIa antibody that antagonizes activin-ActRIIa signaling and improves bone growth/density/strength can fall within scope.
Dependent claims add practical fallback coverage: monoclonal/humanized or fully human formats; combination therapy with a defined list of osteoporosis agents; and broad osteoporosis and oncology-bone indications.
The main litigation risk is mechanism and modality crowding: if prior art already teaches ActRIIa antagonism via activin-ActRIIa signaling for bone outcomes using antibodies, novelty and obviousness pressure increases.
Design-around most likely targets the target/modality or the mechanism framing: avoid anti-ActRIIa antibodies, avoid activin-ActRIIa antagonism as defined, or avoid the specific combination-agent list.
Valuation hinges on specification-level differentiators: if the claims are broad, enforceability tends to depend on whether the patent’s description and prosecution record define distinguishing functional or structural antibody properties.

FAQs

Does Claim 1 cover non-monoclonal antibody formats?
Yes, Claim 1 does not require monoclonality; monoclonal is introduced in dependent Claim 2.
Can a regimen avoid Claims 7-8 and 12-13 by using different co-therapies?
Yes, those dependents require the second bone-active agent to be selected from the enumerated list.
Are oncology indications automatically covered if the cancer is associated with bone loss?
Yes. Claims 18-19 and 23 cover cancers associated with bone loss and cancers associated with bone metastases.
What is the most important limitation for infringement: antibody type or indication?
The antibody-mechanism limitation is the core: an anti-ActRIIa antibody antagonizing activin-ActRIIa signaling. Indication breadth expands exposure but does not replace the mechanism requirement.
Which dependent claims are most likely to matter in enforcement if prior art challenges the breadth?
Claims 2-3 and 10-11 (monoclonal and humanized/fully human) and Claims 7-8 and 12-13 (combination with enumerated bone-active agents) provide narrower fallback angles.

References (APA)

[1] United States Patent 9,480,742.

Title:	Method of promoting bone growth by an anti-actriia antibody
Abstract:	In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density.
Inventor(s):	Knopf; John (Carlisle, MA), Seehra; Jasbir (Lexington, MA)
Assignee:	Acceleron Pharma Inc. (Cambridge, MA)
Application Number:	13/939,976
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	United States Patent 9,480,742: Claim-Scoped Antibody Method Claims Targeting Anti-ActRIIa Signaling US Patent 9,480,742 contains a claim set centered on administering an anti-ActRIIa antibody to promote bone formation and/or improve bone parameters by antagonizing an activin-ActRIIa signaling pathway. The independent claim structure is method-of-treatment oriented, with dependent claims narrowing to antibody format (monoclonal; humanized/fully human) and to combination therapy with established bone-active agents. Dependent claims expand the clinical perimeter to osteoporosis subtypes and cancer-associated bone loss and bone pathology (bone metastases, multiple myeloma, Paget’s disease). This landscape analysis treats the claims as enforceable technology around (i) the biologic target and mechanism (ActRIIa antagonism), (ii) the therapeutic modality (anti-ActRIIa antibodies), and (iii) the method framing (bone growth, density, strength; bone-disorder contexts). The key questions for freedom-to-operate and valuation are: which parts are already crowded by prior art; which limitations meaningfully narrow claim scope; and whether downstream “design-around” options exist that avoid literal claim coverage while still achieving clinical results. What exactly do the claims cover, in enforceable terms? Core independent claim scope (Claim 1 and Claim 9) Claim 1 is a method claim with three technical pillars: Administration element: administering to a subject an “effective amount” of an anti-ActRIIa antibody. Functional mechanism: the antibody antagonizes an activin-ActRIIa signaling pathway. Outcome frame: the method is for “promoting bone growth, increasing bone density, or increasing bone strength.” Claim 9 is a complementary method claim framed as treatment of a bone-related disorder associated with low bone density or decreased bone strength, again using the same therapeutic construct: an anti-ActRIIa antibody antagonizing an activin-ActRIIa signaling pathway. Practical effect: the claims are drafted to capture any anti-ActRIIa antibody that functionally antagonizes activin-ActRIIa signaling when used for bone outcomes, including in specific disorder contexts in dependent claims. Key dependent claim narrowing (Claims 2-3, 10-11) Claim 2 / Claim 10: specifies monoclonal antibody. Claim 3 / Claim 11: specifies humanized or fully human antibody. Practical effect: these dependent claims create layered coverage, but they are not substitutes for Claim 1 and Claim 9. They add fallback positions that can matter if prior art attacks the broader “anti-ActRIIa antibody” phrasing. Combination therapy perimeter (Claims 7-8, 12-13) Claim 7 / Claim 12: adds a second bone-active agent. Claim 8 / Claim 13: restricts the second agent to a defined list: bisphosphonate estrogen selective estrogen-receptor modulator parathyroid hormone calcitonin calcium supplement vitamin D supplement Practical effect: if a competitor runs an anti-ActRIIa antibody program as monotherapy, these dependent claims are not directly invoked. If the competitor uses one of these listed agents in combination, these dependents create sharper infringement hooks. Disorder-specific claims (Claims 14-23) Claim 9 is broadened by dependents to cover specific indications: Osteoporosis subtypes: Claim 14: primary osteoporosis Claim 15: post-menopausal osteoporosis Claim 16: secondary osteoporosis Claim 17: hypogonadal bone loss Cancer-associated bone loss / bone disease: Claim 18: cancer associated with bone loss Claim 19: recipient of cancer treatment regimen associated with bone loss Claim 20: bone metastases Claim 21: multiple myeloma Claim 23: cancer associated with bone metastases Other bone disorder: Claim 22: Paget’s disease Practical effect: this set aims to prevent a competitor from limiting infringement exposure by selecting an alternative bone indication within the osteoporosis and oncology-bone space. What is the claim “center of gravity” that matters for prior art and design-around? 1) Target and mechanism limitation: “anti-ActRIIa antibody” antagonizing “activin-ActRIIa signaling” The most important constraint is not the clinical endpoint. It is the requirement that the administered biologic is an anti-ActRIIa antibody and that it functionally antagonizes activin-ActRIIa signaling. That is a common vulnerability in litigation: prior art often discloses ActRIIa-pathway modulation for bone disorders. If earlier documents disclose antibodies (or antibody-like biologics) that inhibit ActRIIa ligands/signaling to increase bone mass, the novelty may collapse unless the patent claims a specific antibody class, epitope, sequence, binding kinetics, or assay-defined antagonist behavior. 2) Modality type: antibody format The independent claims do not require monoclonality or humanization. Those are introduced via dependents. If the patent owner’s commercial product is a humanized or fully human monoclonal, dependents become valuable in post-prior-art narrowing. But enforceable breadth in Claim 1/9 still reads on non-humanized monoclonals and potentially non-monoclonal anti-ActRIIa antibody formats, depending on claim construction and prosecution history. 3) Combination-agent list The enumerated combination agents are a strong drafting signal. This list can also be used defensively by accused infringers to argue “no listed second bone-active agent” when the combination differs. 4) Indication breadth The indication language is broad enough to cover most osteoporosis and oncology-bone applications. That breadth increases infringement surface area but also heightens prior-art risk because osteoporosis and bone-metastasis bone loss are heavily studied. How strong is the claim set versus typical novelty/obviousness pressure points? Novelty risk: “anti-ActRIIa antibody for bone” is likely already known A rational reading of the claim set suggests the invention is not the mere use of an ActRIIa antagonistic pathway approach. The novelty would have to rest on one or more of the following: a specific class of anti-ActRIIa antibodies, a specific mechanistic interpretation tied to “activin-ActRIIa” vs broader ActRII family signaling, or specific clinical effect framing and/or dosing strategy. Absent such details (the claims provided do not include sequence/epitope/dose/assay thresholds), novelty may depend on the patent’s specification and how it defines “anti-ActRIIa antibody” and “antagonizes” in functional terms. Obviousness risk: ActRIIa-targeted biology is a known translational axis If earlier disclosures teach bone mass improvement via inhibition of ActRIIa signaling, then claiming a method that administers an anti-ActRIIa antibody to improve bone density/strength is the kind of predictable “molecular-to-clinic” adaptation that can trigger obviousness arguments. Dependents specifying humanized/fully human monoclonals can reduce this risk only if prior art lacks that exact modality or functional performance. Indication-specific dependents may not save non-novel core method claims Claims 14-23 likely face a standard argument: even if specific subtypes (e.g., hypogonadal bone loss, Paget’s disease, multiple myeloma) were not individually tested with the claimed antibody, the broader method already predicts bone outcomes if the mechanism is established. That makes the core limitation (anti-ActRIIa antibody antagonizing activin-ActRIIa signaling) the primary battleground. Where is the landscape most crowded: mechanism-first versus antibody-first? Mechanism-first crowding The language “activin-ActRIIa signaling” implies a focus on the activin axis engaging ActRIIa receptors. If the prior art includes inhibition of this axis (or ActRIIa broadly) for bone remodeling, then the landscape is crowded at the mechanism level. Antibody-first crowding Even if the prior art uses ligand traps, soluble receptors, peptides, or non-antibody biologics, Claim 1/9 are specific to antibodies. So crowding depends on whether earlier documents also disclose antibody formats targeting ActRIIa and using functional antagonism language tied to activin signaling. Combination crowding Combination use with osteoporosis standard-of-care (bisphosphonates, estrogen/SERM, PTH, calcitonin, calcium, vitamin D) is common. If earlier documents combine bone agents with an ActRIIa pathway antagonist, then Claims 7-8 and 12-13 face added vulnerability. What would likely be the strongest design-around levers for a competitor? 1) Avoid “anti-ActRIIa antibody” A competitor can aim for: biologics that target a different receptor (e.g., related signaling components) without being anti-ActRIIa, or strategies that use non-antibody modalities. If their mechanism still affects bone outcomes, they may still be clinically competitive, but they reduce direct literal infringement risk if “anti-ActRIIa antibody” is strictly construed. 2) Avoid “antagonizes activin-ActRIIa signaling” If a competitor’s candidate blocks ActRIIa-mediated signaling but not specifically via the activin-ActRIIa pathway, the mechanism limitation may become a litigation focal point. Claim language is functional, so assay definitions matter. 3) Avoid listed combination agents If the competitor uses a combination that omits the enumerated second bone-active agent list, the dependents that require that exact set are harder to reach. 4) Use non-covered indications The claims cover a wide set of bone outcomes and disorders, especially osteoporosis and oncology-bone disease. A narrow, non-overlapping indication could reduce infringement risk, but given the claim breadth, this is less reliable than mechanism or modality design-around. Claim-by-claim infringement surface: what typically triggers exposure Most direct triggers (claims 1 and 9) Any regimen where an anti-ActRIIa antibody is administered to patients for: increased bone density, increased bone strength, or promoting bone growth. Additional triggers If the anti-ActRIIa antibody is explicitly monoclonal and/or humanized/fully human, Claims 2-3 and 10-11 are more accessible as fallback positions. If the regimen includes one of the listed agents, Claims 7-8 and 12-13 expand exposure. If development includes any of the enumerated indications (primary/post-menopausal/secondary osteoporosis; hypogonadal bone loss; Paget’s; multiple myeloma; bone metastases), Claims 14-23 become directly relevant. What does the patent landscape likely look like around this technology? Even without the full citation list here, the claim drafting points to a landscape where multiple players converge on: ActRIIa inhibition for bone mass gains, antibody or antibody-like biologics that neutralize ActRIIa pathway signaling, osteoporosis and cancer-bone indications, and combination regimens with standard osteoporosis drugs. From an investor or R&D portfolio lens, that implies high competition at the mechanism level. In such settings, patents usually succeed when they are drafted with: antibody-specific attributes (sequence, epitope), assay-defined functional thresholds, dosing regimen specifics, or method distinctions that are not obvious from mechanism alone. The claims as provided are mechanism-and-modality broad, suggesting that the value hinges on how the specification and prosecution history define and distinguish “anti-ActRIIa antibody” and “antagonizes activin-ActRIIa signaling,” and on whether earlier documents disclose the same antibody class and functional effects. Key Takeaways Claims 1 and 9 are the core: any anti-ActRIIa antibody that antagonizes activin-ActRIIa signaling and improves bone growth/density/strength can fall within scope. Dependent claims add practical fallback coverage: monoclonal/humanized or fully human formats; combination therapy with a defined list of osteoporosis agents; and broad osteoporosis and oncology-bone indications. The main litigation risk is mechanism and modality crowding: if prior art already teaches ActRIIa antagonism via activin-ActRIIa signaling for bone outcomes using antibodies, novelty and obviousness pressure increases. Design-around most likely targets the target/modality or the mechanism framing: avoid anti-ActRIIa antibodies, avoid activin-ActRIIa antagonism as defined, or avoid the specific combination-agent list. Valuation hinges on specification-level differentiators: if the claims are broad, enforceability tends to depend on whether the patent’s description and prosecution record define distinguishing functional or structural antibody properties. FAQs Does Claim 1 cover non-monoclonal antibody formats? Yes, Claim 1 does not require monoclonality; monoclonal is introduced in dependent Claim 2. Can a regimen avoid Claims 7-8 and 12-13 by using different co-therapies? Yes, those dependents require the second bone-active agent to be selected from the enumerated list. Are oncology indications automatically covered if the cancer is associated with bone loss? Yes. Claims 18-19 and 23 cover cancers associated with bone loss and cancers associated with bone metastases. What is the most important limitation for infringement: antibody type or indication? The antibody-mechanism limitation is the core: an anti-ActRIIa antibody antagonizing activin-ActRIIa signaling. Indication breadth expands exposure but does not replace the mechanism requirement. Which dependent claims are most likely to matter in enforcement if prior art challenges the breadth? Claims 2-3 and 10-11 (monoclonal and humanized/fully human) and Claims 7-8 and 12-13 (combination with enumerated bone-active agents) provide narrower fallback angles. References (APA) [1] United States Patent 9,480,742. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	NATPARA	parathyroid hormone	For Injection	125511	January 23, 2015	⤷ Start Trial	2033-07-11
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 9,480,742

Summary for Patent: 9,480,742