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United States Patent 7,655,428: What Do the Claims Really Cover, and Where Is the Landscape Crowded?

United States Patent 7,655,428 (“US7655428”) claims immunoassay methods for detecting latent protein C in patient-derived bodily fluids using monoclonal antibodies that bind latent protein C while minimizing cross-reactivity with activated protein C. The claim set is built around a specific antibody competition format and specific antibody variable regions (heavy chain SEQ ID NO:6; light chain SEQ ID NO:7), then broadened through assay modality (sandwich vs competitive), signal generation (electrochemical or optical), sample type (blood, serum, plasma), and performance windows (1 to 5 μg/mL; selectivity vs active protein C at multiple fold-improvement thresholds).

The patent’s enforceable core sits in the antibody specificity and competition framing in Claim 1. Downstream claims then attempt to capture variations in assay format and signal readout that are common in immunoassay platforms, with added constraints tying sensitivity to latent protein C peptides and suppressing signal from activated protein C.

How Broad Are Claim 1 and the Antibody-Specific Core?

Claim 1 is a narrow antibody-method claim with a functional specificity limit

Claim 1 requires all of the following:

Method type: immunoassay method for detection of latent protein C in a patient bodily-fluid sample.
Antibody: monoclonal antibody that:
- specifically binds latent protein C
- does not significantly cross-react with activated protein C
Competition element: the antibody “competes with” an antibody with:
- heavy chain variable region sequence SEQ ID NO:6
- light chain variable region sequence SEQ ID NO:7
Detection & quantification:
- detect amount of antibody bound to latent protein C
- calculate latent protein C concentration based on bound antibody amount

This is not a generic “latent vs active protein C assay” claim. It is engineered around a particular competitive antibody relationship and a specific variable-region identity for the competing reference antibody.

Key enforceability implication: the “competes with” requirement can narrow infringement

Even if a product uses an antibody that binds latent protein C and ignores active protein C, it may still avoid infringement if the antibody does not satisfy the competition construct against the specific reference antibody with SEQ ID NO:6 and SEQ ID NO:7. In practice, “competes with” is often litigated through competition binding assays (e.g., displacement curves, epitope binning).

What the claim does cover even if assay formats differ is the antibody-property requirement: the antibody must behave as a latent-selective binder with minimal active cross-reactivity.

What Do Dependent Claims Add, and Where Do They Create Potential Design-Arounds?

Clinical framing and sample scope (Claims 2, 3, 13)

Claim 2: patient is human
Claim 3: patient has or is suspected of systemic inflammatory response syndrome (SIRS)
Claim 13: sample is blood, serum, or plasma

These additions are not antibody-specific, but they can matter for enforcement if accused methods are used in non-human contexts or alternate clinical syndromes. Most labs, however, will use serum/plasma and humans, so these are usually not meaningful design-around levers by themselves.

Assay format breadth (Claims 4 to 8)

Claim 4: sandwich immunoassay method
Claim 5: sandwich configuration using:
- first antibody on a solid phase
- second antibody on a signal development element
- one or both antibodies sensitive for latent relative to activated
- signal indicates protein bound by both antibodies
Claim 6: competitive immunoassay method
Claim 7: latent protein C conjugated to solid phase plus an antibody on signal element (latent-selective antibody)
Claim 8: latent protein C conjugated to signal element plus antibody on solid phase (latent-selective antibody)

Landscape implication: immunoassay format (sandwich/competitive) is broadly used across protein quantification. The differentiator in this patent is not format alone; it is latent-selective antibody behavior and (for Claim 1) competition against the SEQ ID reference antibody.

A sophisticated design-around strategy would target:

replacing the antibody with one that binds latent but has some cross-reactivity with activated protein C, or
using antibodies that do not satisfy the competition relationship.

Signal generation options (Claims 9 to 12)

Claim 9: electrochemical signal
Claim 10: antibody-based biosensor
Claim 11: optical signal
Claim 12: fluorometer

These are typical detection modes. By themselves, they usually do not avoid infringement if the method otherwise meets the antibody and assay requirements.

Performance characteristics tied to specific latent protein C sequence window (Claims 14 to 18)

The patent ties detectable signal capability to latent protein C having a sequence “depicted by residues 43-461 of SEQ ID NO:1,” with concentration and selectivity thresholds.

Claim 14: detectable signal when latent protein C (residues 43-461 of SEQ ID NO:1) is 1 to 5 μg/mL
Claim 15: detectable signal from 3 μg/mL latent protein C that is at least 5-fold greater than signal from equimolar active protein C
Claim 16: at least 10-fold greater (from 3 μg/mL latent)
Claim 17: at least 25-fold greater (from 3 μg/mL latent)
Claim 18: combines 5-fold relative performance at 3 μg/mL and also concentration window 1 to 5 μg/mL

Critical take: these are not universal assay characteristics; they are numerical thresholds that depend on assay conditions, antibody affinities, calibration curve logic, conjugation chemistry, and detection instrumentation. If an accused assay yields different fold selectivity (for example 2x or 4x), it may not satisfy these dependent claim limits, even if it satisfies Claim 1’s antibody specificity in theory.

Enforcement strategy likely used by the patentee: assert independent Claim 1 as the anchor, then pile on dependent claims where assay performance meets the numerical ranges.

Chelators and tested sample context (Claim 19)

Claim 19: sample contains a chelating agent

This reads like a stabilization or interference-control constraint. Design-around would avoid chelator incorporation if it is not required to maintain assay performance.

Antibody humanization and equivalence (Claim 20)

Claim 20: antibody is human, humanized, chimeric, or veneered

This widens coverage beyond fully murine monoclonals. It also signals that the patent expects commercial antibodies to be engineered for human use, which affects both licensing and infringement risk for diagnostics built around human-compatible monoclonals.

Activated protein C context (Claims 21 to 23)

Claim 21: activated protein C is endogenous to patient
Claim 22: activated protein C has been administered as a pharmaceutical preparation
Claim 23: preparation is drotrecogin alfa

This is a targeted clinical scenario. Drotrecogin alfa (rhAPC) is a known recombinant activated protein C product; the patent implies use where active protein C already exists at measurable levels, making latent-only discrimination valuable.

Where Is the Patent Likely Strongest, and Where Does It Look Vulnerable?

Strongest areas

Antibody specificity + minimal cross-reactivity
The explicit “does not significantly cross-react with activated protein C” requirement anchors the patent’s novelty around discriminating latent vs activated forms.
Competition requirement against an antibody defined by SEQ ID NO:6 and SEQ ID NO:7
This can be powerful if the reference antibody is itself broadly used in the field or if competitors are forced to use the same epitope bin to achieve selectivity.
Performance thresholds in dependent claims
Numerical selectivity (5x/10x/25x over equimolar active protein C) can provide an additional filter for infringement when evidence shows a particular assay yields sufficient discrimination.

Vulnerable areas / likely design-arounds

“Competes with” as a potential technical boundary
If competitors develop monoclonals that bind latent and are low-cross-reactive but bind a different epitope (not competing with the SEQ ID reference antibody), they can avoid Claim 1 while still achieving practical latent detection.
Dependent claim reliance on assay-achieved performance
Dependent performance thresholds can be missed if the accused assay uses different calibration logic or yields different fold-selectivity.
Chelator and biosensor-specific constraints
Claims like Claim 19 and Claim 10 can be avoided by different sample preparation or readout architectures.

How Does the Claim Language Map to Typical Diagnostic Platform Variants?

Sandwich vs competitive formats

Sandwich (Claims 4-5) requires two antibodies that both capture/bind the target complex. The latent-selectivity constraint must hold for at least one antibody (or both).
Competitive (Claims 6-8) uses labeled latent protein C and a latent-selective antibody that competes for binding.

Competitors can choose the format that best matches their antibody pair strategy. The patent’s format flexibility raises potential infringement exposure if the antibody specificity is met.

Signal modality

Electrochemical and optical readouts are both covered. If the patent covers the antibody-method core (Claim 1), platform change usually does not eliminate infringement risk.

Patent Landscape: What the Claim Set Suggests About Prior Art and Coexistence

You provided only the claim text. Without the actual patent specification, prosecution history, cited references, and family data, a full landscape cannot be grounded to named patents, assignees, or document-specific claim charts. Under the constraints of producing complete and accurate landscape content, no further patent-identifying analysis can be generated from the claim text alone.

What can be inferred strictly from the claim structure is the likely landscape fault line:

Most likely crowded patent territory

Protein C immunoassays distinguishing latent vs activated species.
Monoclonal antibodies against protein C forms with minimized cross-reactivity.
Electrochemical and optical immunosensor formats for protein biomarker quantification.
Clinical use cases involving SIRS and recombinant activated protein C exposure (drotrecogin alfa).

Least crowded or more strategically protected territory

Antibodies that satisfy competition against a reference antibody defined by SEQ ID NO:6/SEQ ID NO:7.
Methods engineered to hit specific fold-discrimination thresholds (5x/10x/25x) between latent and active protein C at specified concentrations.

Operational Claim-to-Action: What a Competitor Must Do to Avoid the Core

Based on Claim 1 language, design-around tactics must address at least one of these gating elements:

Remove the latent-selective specificity standard
- Ensure measurable cross-reactivity with activated protein C that is not “not significant.”
  (This is a direct attack on Claim 1’s functional limitation.)
Change the competitive epitope relationship
- Use monoclonal antibodies that bind latent protein C but do not compete with the specific SEQ ID NO:6/SEQ ID NO:7 reference antibody.
Avoid hitting dependent performance windows
- Engineer calibration conditions so fold-selectivity versus active protein C does not meet the dependent thresholds (5x/10x/25x) and/or concentration-response constraints.
Avoid dependent structural limitations
- If pursuing narrower freedom-to-operate, avoid formats that match dependent claim structure (sandwich/competitive conjugate placements), and avoid chelator use if the method follows Claim 19.

Key Takeaways

US7655428 is anchored in antibody behavior, not just an immunoassay concept: the method requires a monoclonal antibody that binds latent protein C and does not significantly cross-react with activated protein C.
Claim 1 adds a competition requirement against a specific reference antibody defined by SEQ ID NO:6 (heavy variable) and SEQ ID NO:7 (light variable), which can be the central design-around lever.
Dependent claims broaden platform and clinical context (human; SIRS; sandwich/competitive; electrochemical/optical; blood/serum/plasma; drotrecogin alfa exposure) but also add numerical performance thresholds that may be harder to meet outside the patentee’s assay conditions.
The landscape implication from the claim set is that latent-vs-active discrimination is the contested axis, and the strongest protection is likely in antibody epitope/competition control plus demonstrated selectivity.

FAQs

What is the key novelty element of US7655428’s claims?
The immunoassay requires a monoclonal antibody that specifically binds latent protein C while not significantly cross-reacting with activated protein C, plus a competition relationship tied to SEQ ID NO:6 and SEQ ID NO:7.
Does the patent cover both sandwich and competitive immunoassays?
Yes. Claims cover sandwich (Claims 4-5) and competitive formats (Claims 6-8), with latent-selective antibodies or conjugates.
Do the claims cover different signal readouts?
Yes. They cover electrochemical signals and antibody-based biosensors (Claims 9-10), and optical signals including fluorometer readouts (Claims 11-12).
What do the fold-improvement limits mean?
Dependent claims require that at a specified latent protein C concentration (notably 3 μg/mL), the signal is at least 5x, 10x, or 25x greater than equimolar activated protein C.
Where does drotrecogin alfa enter the claim set?
Through dependent claims that define scenarios where activated protein C has been administered, with Claim 23 specifying drotrecogin alfa.

References

[1] United States Patent 7,655,428 (US7655428), claim set as provided in prompt.

Title:	Latent protein C assays and their uses for diagnosis and/or prognosis in systemic inflammatory response syndromes
Abstract:	The present invention relates to methods and compositions for measuring latent protein C in test samples, particularly patient samples. The methods and compositions described are sensitive for latent protein C, relative to activated protein C.
Inventor(s):	Valkirs; Gunars E. (Escondido, CA), Buechler; Joseph A. (Carlsbad, CA), Lee; Seok-Won (San Diego, CA), Veeramallu; Uday Kumar (San Diego, CA)
Assignee:	Biosite, Inc. (Waltham, MA)
Application Number:	11/614,836
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	United States Patent 7,655,428: What Do the Claims Really Cover, and Where Is the Landscape Crowded? United States Patent 7,655,428 (“US7655428”) claims immunoassay methods for detecting latent protein C in patient-derived bodily fluids using monoclonal antibodies that bind latent protein C while minimizing cross-reactivity with activated protein C. The claim set is built around a specific antibody competition format and specific antibody variable regions (heavy chain SEQ ID NO:6; light chain SEQ ID NO:7), then broadened through assay modality (sandwich vs competitive), signal generation (electrochemical or optical), sample type (blood, serum, plasma), and performance windows (1 to 5 μg/mL; selectivity vs active protein C at multiple fold-improvement thresholds). The patent’s enforceable core sits in the antibody specificity and competition framing in Claim 1. Downstream claims then attempt to capture variations in assay format and signal readout that are common in immunoassay platforms, with added constraints tying sensitivity to latent protein C peptides and suppressing signal from activated protein C. How Broad Are Claim 1 and the Antibody-Specific Core? Claim 1 is a narrow antibody-method claim with a functional specificity limit Claim 1 requires all of the following: Method type: immunoassay method for detection of latent protein C in a patient bodily-fluid sample. Antibody: monoclonal antibody that: specifically binds latent protein C does not significantly cross-react with activated protein C Competition element: the antibody “competes with” an antibody with: heavy chain variable region sequence SEQ ID NO:6 light chain variable region sequence SEQ ID NO:7 Detection & quantification: detect amount of antibody bound to latent protein C calculate latent protein C concentration based on bound antibody amount This is not a generic “latent vs active protein C assay” claim. It is engineered around a particular competitive antibody relationship and a specific variable-region identity for the competing reference antibody. Key enforceability implication: the “competes with” requirement can narrow infringement Even if a product uses an antibody that binds latent protein C and ignores active protein C, it may still avoid infringement if the antibody does not satisfy the competition construct against the specific reference antibody with SEQ ID NO:6 and SEQ ID NO:7. In practice, “competes with” is often litigated through competition binding assays (e.g., displacement curves, epitope binning). What the claim does cover even if assay formats differ is the antibody-property requirement: the antibody must behave as a latent-selective binder with minimal active cross-reactivity. What Do Dependent Claims Add, and Where Do They Create Potential Design-Arounds? Clinical framing and sample scope (Claims 2, 3, 13) Claim 2: patient is human Claim 3: patient has or is suspected of systemic inflammatory response syndrome (SIRS) Claim 13: sample is blood, serum, or plasma These additions are not antibody-specific, but they can matter for enforcement if accused methods are used in non-human contexts or alternate clinical syndromes. Most labs, however, will use serum/plasma and humans, so these are usually not meaningful design-around levers by themselves. Assay format breadth (Claims 4 to 8) Claim 4: sandwich immunoassay method Claim 5: sandwich configuration using: first antibody on a solid phase second antibody on a signal development element one or both antibodies sensitive for latent relative to activated signal indicates protein bound by both antibodies Claim 6: competitive immunoassay method Claim 7: latent protein C conjugated to solid phase plus an antibody on signal element (latent-selective antibody) Claim 8: latent protein C conjugated to signal element plus antibody on solid phase (latent-selective antibody) Landscape implication: immunoassay format (sandwich/competitive) is broadly used across protein quantification. The differentiator in this patent is not format alone; it is latent-selective antibody behavior and (for Claim 1) competition against the SEQ ID reference antibody. A sophisticated design-around strategy would target: replacing the antibody with one that binds latent but has some cross-reactivity with activated protein C, or using antibodies that do not satisfy the competition relationship. Signal generation options (Claims 9 to 12) Claim 9: electrochemical signal Claim 10: antibody-based biosensor Claim 11: optical signal Claim 12: fluorometer These are typical detection modes. By themselves, they usually do not avoid infringement if the method otherwise meets the antibody and assay requirements. Performance characteristics tied to specific latent protein C sequence window (Claims 14 to 18) The patent ties detectable signal capability to latent protein C having a sequence “depicted by residues 43-461 of SEQ ID NO:1,” with concentration and selectivity thresholds. Claim 14: detectable signal when latent protein C (residues 43-461 of SEQ ID NO:1) is 1 to 5 μg/mL Claim 15: detectable signal from 3 μg/mL latent protein C that is at least 5-fold greater than signal from equimolar active protein C Claim 16: at least 10-fold greater (from 3 μg/mL latent) Claim 17: at least 25-fold greater (from 3 μg/mL latent) Claim 18: combines 5-fold relative performance at 3 μg/mL and also concentration window 1 to 5 μg/mL Critical take: these are not universal assay characteristics; they are numerical thresholds that depend on assay conditions, antibody affinities, calibration curve logic, conjugation chemistry, and detection instrumentation. If an accused assay yields different fold selectivity (for example 2x or 4x), it may not satisfy these dependent claim limits, even if it satisfies Claim 1’s antibody specificity in theory. Enforcement strategy likely used by the patentee: assert independent Claim 1 as the anchor, then pile on dependent claims where assay performance meets the numerical ranges. Chelators and tested sample context (Claim 19) Claim 19: sample contains a chelating agent This reads like a stabilization or interference-control constraint. Design-around would avoid chelator incorporation if it is not required to maintain assay performance. Antibody humanization and equivalence (Claim 20) Claim 20: antibody is human, humanized, chimeric, or veneered This widens coverage beyond fully murine monoclonals. It also signals that the patent expects commercial antibodies to be engineered for human use, which affects both licensing and infringement risk for diagnostics built around human-compatible monoclonals. Activated protein C context (Claims 21 to 23) Claim 21: activated protein C is endogenous to patient Claim 22: activated protein C has been administered as a pharmaceutical preparation Claim 23: preparation is drotrecogin alfa This is a targeted clinical scenario. Drotrecogin alfa (rhAPC) is a known recombinant activated protein C product; the patent implies use where active protein C already exists at measurable levels, making latent-only discrimination valuable. Where Is the Patent Likely Strongest, and Where Does It Look Vulnerable? Strongest areas Antibody specificity + minimal cross-reactivity The explicit “does not significantly cross-react with activated protein C” requirement anchors the patent’s novelty around discriminating latent vs activated forms. Competition requirement against an antibody defined by SEQ ID NO:6 and SEQ ID NO:7 This can be powerful if the reference antibody is itself broadly used in the field or if competitors are forced to use the same epitope bin to achieve selectivity. Performance thresholds in dependent claims Numerical selectivity (5x/10x/25x over equimolar active protein C) can provide an additional filter for infringement when evidence shows a particular assay yields sufficient discrimination. Vulnerable areas / likely design-arounds “Competes with” as a potential technical boundary If competitors develop monoclonals that bind latent and are low-cross-reactive but bind a different epitope (not competing with the SEQ ID reference antibody), they can avoid Claim 1 while still achieving practical latent detection. Dependent claim reliance on assay-achieved performance Dependent performance thresholds can be missed if the accused assay uses different calibration logic or yields different fold-selectivity. Chelator and biosensor-specific constraints Claims like Claim 19 and Claim 10 can be avoided by different sample preparation or readout architectures. How Does the Claim Language Map to Typical Diagnostic Platform Variants? Sandwich vs competitive formats Sandwich (Claims 4-5) requires two antibodies that both capture/bind the target complex. The latent-selectivity constraint must hold for at least one antibody (or both). Competitive (Claims 6-8) uses labeled latent protein C and a latent-selective antibody that competes for binding. Competitors can choose the format that best matches their antibody pair strategy. The patent’s format flexibility raises potential infringement exposure if the antibody specificity is met. Signal modality Electrochemical and optical readouts are both covered. If the patent covers the antibody-method core (Claim 1), platform change usually does not eliminate infringement risk. Patent Landscape: What the Claim Set Suggests About Prior Art and Coexistence You provided only the claim text. Without the actual patent specification, prosecution history, cited references, and family data, a full landscape cannot be grounded to named patents, assignees, or document-specific claim charts. Under the constraints of producing complete and accurate landscape content, no further patent-identifying analysis can be generated from the claim text alone. What can be inferred strictly from the claim structure is the likely landscape fault line: Most likely crowded patent territory Protein C immunoassays distinguishing latent vs activated species. Monoclonal antibodies against protein C forms with minimized cross-reactivity. Electrochemical and optical immunosensor formats for protein biomarker quantification. Clinical use cases involving SIRS and recombinant activated protein C exposure (drotrecogin alfa). Least crowded or more strategically protected territory Antibodies that satisfy competition against a reference antibody defined by SEQ ID NO:6/SEQ ID NO:7. Methods engineered to hit specific fold-discrimination thresholds (5x/10x/25x) between latent and active protein C at specified concentrations. Operational Claim-to-Action: What a Competitor Must Do to Avoid the Core Based on Claim 1 language, design-around tactics must address at least one of these gating elements: Remove the latent-selective specificity standard Ensure measurable cross-reactivity with activated protein C that is not “not significant.” (This is a direct attack on Claim 1’s functional limitation.) Change the competitive epitope relationship Use monoclonal antibodies that bind latent protein C but do not compete with the specific SEQ ID NO:6/SEQ ID NO:7 reference antibody. Avoid hitting dependent performance windows Engineer calibration conditions so fold-selectivity versus active protein C does not meet the dependent thresholds (5x/10x/25x) and/or concentration-response constraints. Avoid dependent structural limitations If pursuing narrower freedom-to-operate, avoid formats that match dependent claim structure (sandwich/competitive conjugate placements), and avoid chelator use if the method follows Claim 19. Key Takeaways US7655428 is anchored in antibody behavior, not just an immunoassay concept: the method requires a monoclonal antibody that binds latent protein C and does not significantly cross-react with activated protein C. Claim 1 adds a competition requirement against a specific reference antibody defined by SEQ ID NO:6 (heavy variable) and SEQ ID NO:7 (light variable), which can be the central design-around lever. Dependent claims broaden platform and clinical context (human; SIRS; sandwich/competitive; electrochemical/optical; blood/serum/plasma; drotrecogin alfa exposure) but also add numerical performance thresholds that may be harder to meet outside the patentee’s assay conditions. The landscape implication from the claim set is that latent-vs-active discrimination is the contested axis, and the strongest protection is likely in antibody epitope/competition control plus demonstrated selectivity. FAQs What is the key novelty element of US7655428’s claims? The immunoassay requires a monoclonal antibody that specifically binds latent protein C while not significantly cross-reacting with activated protein C, plus a competition relationship tied to SEQ ID NO:6 and SEQ ID NO:7. Does the patent cover both sandwich and competitive immunoassays? Yes. Claims cover sandwich (Claims 4-5) and competitive formats (Claims 6-8), with latent-selective antibodies or conjugates. Do the claims cover different signal readouts? Yes. They cover electrochemical signals and antibody-based biosensors (Claims 9-10), and optical signals including fluorometer readouts (Claims 11-12). What do the fold-improvement limits mean? Dependent claims require that at a specified latent protein C concentration (notably 3 μg/mL), the signal is at least 5x, 10x, or 25x greater than equimolar activated protein C. Where does drotrecogin alfa enter the claim set? Through dependent claims that define scenarios where activated protein C has been administered, with Claim 23 specifying drotrecogin alfa. References [1] United States Patent 7,655,428 (US7655428), claim set as provided in prompt. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	XIGRIS	drotrecogin alfa	Injection	125029	November 21, 2001	7,655,428	2026-12-21
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 7,655,428

Summary for Patent: 7,655,428