Patent: 9,707,269

Summary for Patent: 9,707,269

Title:	Sugar compositions for treating hemophilia A and/or von Willebrand disease
Abstract:	The invention relates to compositions comprising an isolated sugar for use in the treatment of von Willebrand disease and/or hemophilia A, wherein the sugar is an accessible sugar residue derived from ABO(H) blood group antigen.
Inventor(s):	Schulte; Stefan (Marburg, DE), Spirig; Rolf (Bern, CH), Zollner; Sabine (Muri, CH), Moses; Michael (Graevenwiesbach, DE), Wormsbaecher; Wilfried (Kirchhain, DE), Stoehr; Hans-Arnold (Wetter, DE)
Assignee:	CSL BEHRING GMBH (Marburg, DE)
Application Number:	14/399,326
Patent Claims:	see list of patent claims

United States Patent 9,707,269 (vWF half-life extension using ABO(H)-derived sugar inhibitors): claim-by-claim dissection, enforceable scope, and US patent landscape

Executive summary: US 9,707,269 claims a method for increasing circulating von Willebrand factor (vWF) half-life in hemophilia A and/or von Willebrand disease by co-administering exogenous vWF with an isolated monosaccharide (unmodified galactose, fucose, and/or N-acetylgalactosamine) derived from ABO(H) blood group antigen that inhibits vWF clearance via its receptor (including specific C-type lectin-like receptors and SCARA5). The enforceable claim center of gravity is the combination: exogenous vWF + an ABO(H)-accessible monosaccharide that blocks vWF clearance receptor binding/uptake, with downstream PK outcomes (reduced in vivo clearance, increased factor VIII AUC). The claim set is narrow on sugar identity (unmodified galactose/fucose/GalNAc) and broad on vWF source (plasma-derived or recombinant) and receptor biology (multiple receptor families named or encompassed). The competitive risk is that designs using other glycan structures, modified sugars, other ABO-derived residues, or different clearance blockers could evade claim scope unless they still read on the monosaccharide limitation and functional inhibition of vWF clearance receptor interaction.

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What is US Patent 9,707,269 claiming for vWF half-life extension and why does it matter?

US 9,707,269 claims a therapeutic method with a two-component functional mechanism:

1. Provide exogenous vWF to a subject with hemophilia A and/or von Willebrand disease.
2. Co-administer an isolated sugar that inhibits vWF interaction with its clearance receptor, where the sugar is explicitly an ABO(H)-accessible sugar residue derived from ABO(H) blood group antigen, and the sugar is limited to monosaccharides that are unmodified galactose, fucose, and/or N-acetylgalactosamine (GalNAc).

Claim core (independent claim 1)

The independent claim 1 is a method claim with these essential limitations:

• Subject: “a subject with hemophilia A and/or von Willebrand disease.”
• Administering a composition comprising:
  • exogenous vWF (any form unless limited later): the claim does not restrict source in claim 1.
  • an isolated sugar that inhibits interaction of vWF with its clearance receptor.
• Sugar identity limitation:
  • “accessible sugar residue derived from ABO(H) blood group antigen”
  • the sugar is “one or more of unmodified galactose, fucose, and N-acetylgalactosamine”
  • the sugar is a “monosaccharide”
• Mechanistic target: inhibition of vWF clearance receptor interaction (receptor is further defined in dependent claims).

This claim reads like a functional mechanism wrapped in strict chemical identity.

Dependent claims narrow the execution and increase specificity

• Claim 2: reduces in vivo clearance of vWF.
• Claim 3: reduced clearance leads to increased factor VIII AUC.
• Claim 4: exogenous vWF is plasma derived.
• Claim 5: exogenous vWF is recombinant.
• Claim 6: sugar/vWF composition timing: administered prior to vWF administration.
• Claims 7-10: receptor specificity:
  • Claim 7: “C-type lectin-like receptor”
  • Claim 8: subgroup list: asialoglycoprotein, DC receptors, collectins
  • Claim 9: named receptors: ASGPR (CLEC4M), CLEC10A, CLEC4F, Collectin-12
  • Claim 10: class A scavenger receptor comprising SCARA5

Practical consequence for enforceability

The sugar limitation is likely the hardest part to design around if a competitor uses the same monosaccharides in a context where they inhibit vWF clearance receptor interactions. Conversely, competitors can attempt to avoid by using:

• different sugar structures (disaccharides/oligosaccharides),
• modified monosaccharides,
• alternative ABO-derived residues not captured by “unmodified galactose, fucose, GalNAc,”
• different clearance blockade mechanisms unrelated to vWF clearance receptor interaction,
• different co-administration logic (e.g., simultaneous rather than “prior to” administration if claim 6 is asserted).

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How strong are the patent claims: novelty and enforceability risk points?

Potential novelty hinges

The claim is structured around a known clearance concept (vWF clearance receptors) but narrows to:

• exogenous vWF co-administration, and
• ABO(H)-derived unmodified monosaccharides that block vWF clearance receptor interaction.

In US practice, novelty and non-obviousness would likely turn on whether earlier art disclosed:

• using ABO(H) blood group antigen monosaccharide residues (galactose/fucose/GalNAc),
• specifically as inhibitors of vWF clearance receptor interaction,
• in combination with exogenous vWF to increase vWF half-life.

If earlier disclosures existed for sugar inhibition of clearance of other glycoproteins, they may not be directly anticipatory for vWF half-life augmentation with exogenous vWF. That said, obviousness can still be argued if clearance receptor biology is well established and the sugar residues are routine to screen.

Functional limitation risk: “inhibits interaction”

The claim does not require a particular assay or binding endpoint. This increases enforceability if the function is met, but it also creates litigation complexity:

• how courts construe “interaction” and “inhibits,”
• whether partial inhibition is sufficient,
• what receptor engagement definition applies when multiple receptors exist.

Composition vs method boundaries

The claim is a method of increasing half-life. Practically, infringement turns on method performance: administering the sugar + exogenous vWF to the subject. A product company can be exposed even if it sells components separately, depending on induced/contributory infringement theories and evidence of intended use.

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What do claims 1-3 require for infringement: PK outcome linkage to factor VIII AUC?

Claim 1: minimum infringement elements

To infringe claim 1, a defendant must practice:

• method on a subject with hemophilia A and/or VWD,
• administration of exogenous vWF,
• plus isolated unmodified monosaccharide(s) (galactose/fucose/GalNAc) derived from ABO(H),
• where the sugar inhibits vWF clearance receptor interaction.

No explicit requirement for factor VIII AUC is in claim 1, only for half-life increase.

Claim 2: reduced clearance

Claim 2 adds a measurement element:

• in vivo clearance of vWF is reduced.

Enforcement could rely on standard PK analytics showing clearance reduction in the treated subject.

Claim 3: factor VIII AUC increase

Claim 3 ties vWF clearance reduction to a downstream PK effect:

• reduction of vWF clearance leads to a concomitant increase in factor VIII AUC.

This introduces a tighter causal relationship. In litigation, defendants could contest whether increased factor VIII AUC is “concomitant” and attributable to the intervention, versus background variability or alternative mechanisms.

Design-around angle: competitors could still practice claim 1’s mechanism without achieving a factor VIII AUC increase threshold, but that is unlikely if the pathway is mechanistically correct (vWF stabilizes factor VIII). Still, the claim 3 requirement gives a potential evidentiary hurdle.

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Which vWF products are covered: plasma-derived vs recombinant?

Claim 4 and Claim 5

The patent explicitly covers both:

• plasma-derived exogenous vWF (claim 4), and
• recombinant exogenous vWF (claim 5).

That matters because the vWF molecule used in therapy is often a differentiator in patent and market strategy. The presence of both dependent claims indicates the drafter anticipated multiple manufacturing platforms and intended coverage regardless of vWF origin.

Competitive implication: partnering with a vWF manufacturer or using an approved vWF product does not remove coverage if the sugar inhibitor component and receptor-inhibition conditions are met.

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What does the administration timing limitation in claim 6 change?

Claim 6 requires:

• composition is administered prior to administration of von Willebrand factor.

This is a practical operational design point:

• If a product label or clinical protocol administers sugar at the same time as vWF, or after vWF, claim 6 may not read.
• Claim 1 does not contain a “prior to” requirement. So claim 6 is likely an additional narrow hook rather than the core.

Risk profile: if the infringement theory is “administered composition comprising exogenous vWF and sugar,” claim 1 could still be asserted even if timing is contested, because claim 1 is not framed as pre-dosing only. Claim 6 could be asserted to strengthen a timing-based infringement theory.

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How specific are the receptor limitations in claims 7-10?

The dependent receptor claims are structured in layers.

Claim 7: C-type lectin-like receptor

This covers receptor families involved in glycoprotein clearance.

Claim 8: receptor subgroups

• asialoglycoprotein
• DC receptors
• collectins

Claim 9: named receptors

• ASGPR (with CLEC4M listed)
• CLEC10A
• CLEC4F
• Collectin-12

Claim 10: class A scavenger receptor including SCARA5

This explicitly captures SCARA5.

Litigation and design-around angle:

• If vWF clearance is mediated by multiple receptors in vivo, a defendant could argue that their sugar does not inhibit the interactions through the specifically claimed receptor(s).
• However, claim 1 does not limit to a particular receptor class, only that the sugar inhibits vWF interaction with its clearance receptor. Dependent claims narrow the receptor identity but do not restrict claim 1.

In practice, receptor-specific dependent claims give multiple independent “entry points” for proving infringement based on receptor biology, but claim 1 is broader.

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What is the likely US patent landscape around vWF half-life prolongation using glycan or sugar inhibitors?

How to map the landscape (high-level categories)

Even without listing every potentially related US patent number, the surrounding US landscape for vWF half-life extension typically clusters into:

1. vWF products (plasma-derived or recombinant) and their use for bleeding disorders.
2. vWF engineering to alter clearance or stability (glycoengineering, Fc fusion, domain modifications).
3. Clearance receptor modulation for glycoprotein half-life control (lectins, scavenger receptors, etc.).
4. Glycan interactions with clearance receptors using sugars, sialylated/unsialylated epitopes, ABO-related residues, or mimetics.
5. Combination regimens with co-therapies to enhance factor VIII stabilization (since vWF stabilizes factor VIII).

US 9,707,269 sits at the intersection: clearance receptor modulation with a defined monosaccharide identity and exogenous vWF co-administration.

Potential near-neighbor claim themes competitors would face

Companies developing “half-life extension” strategies generally need to clear three IP risks:

• blocking patents on sugar inhibitors,
• blocking patents on vWF clearance receptor pathways,
• blocking patents on co-administration methods that produce PK improvements.

The presence of explicit receptor names (CLEC4M, CLEC10A, CLEC4F, Collectin-12, SCARA5) suggests the inventors staked a broad but receptor-aware position. If prior art exists on those receptors with other ligands, it may be used to attack obviousness; if prior art exists on vWF clearance with sugar residues, it can be used to attack novelty.

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What other patents could be asserted in parallel with 9,707,269 (and where would they attack)?

Patent estate likely to attach at three layers

1. Core method layer: co-administration of exogenous vWF with the ABO(H)-monosaccharide inhibitor to increase vWF half-life.
2. Product-use layer: indications for hemophilia A and/or VWD using vWF products and stabilizing factor VIII via vWF.
3. Receptor-pathway layer: patents directed to clearance receptors (including C-type lectin-like receptors and SCARA5) and ligands that modulate vWF clearance.

Critical litigation point: If a company uses the patented sugar residues but uses a different vWF formulation route, or a different co-administration timing, claim 1 can still be asserted, while dependent claims (4-6, 7-10) can broaden or narrow the infringement theory.

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When does US 9,707,269 expire and how does that shape generic or competitive entry risk?

The patent term and any adjustments or terminal disclaimers govern exclusivity. Without the patent’s filing date, provisional priority, and term adjustment details, a precise expiration date cannot be stated from the information provided.

Commercially actionable view: the infringement risk persists through the term and any enforceable adjustment. For a new entrant, the key is whether any competing regimen has to include:

• exogenous vWF,
• unmodified galactose/fucose/GalNAc derived from ABO(H),
• clearance receptor interaction inhibition, in the claimed patient setting.

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How would competitors design around claim 1’s sugar limitation?

Design-around strategies with high likelihood

• Use modified sugars (e.g., acetylated/derivatized forms) rather than “unmodified” residues.
• Use disaccharides/oligosaccharides rather than “monosaccharide” residues.
• Use ABO(H)-derived epitopes that are not restricted to unmodified galactose/fucose/GalNAc monosaccharides.
• Use a clearance inhibitor that works through a different mechanism and does not “inhibit the interaction of vWF with its clearance receptor” (as construed by courts).

Design-around strategies with lower likelihood

• Switching vWF source (plasma vs recombinant). The patent covers both via dependent claims 4 and 5.
• Changing receptor assumptions, since claim 1 does not restrict receptor identity; only dependent claims do.

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Which legal theories are most likely in US enforcement of 9,707,269?

Direct infringement

A sponsor administering a regimen to patients that uses the claimed sugar residues to inhibit vWF clearance receptor interaction while administering exogenous vWF could be directly liable.

Induced/contributory infringement

If the sponsor sells:

• the sugar inhibitor (or formulation) with instructions or labeling that induce use with exogenous vWF for the claimed method, indirect infringement theories may apply.

Claim construction pressure points

• Interpretation of “isolated sugar,” “accessible sugar residue derived from ABO(H),” and “unmodified.”
• Scope of “inhibits interaction,” particularly with receptor biology where multiple receptors can contribute.

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Key takeaways

• US 9,707,269 is centered on a narrow chemical identity: isolated unmodified ABO(H)-accessible monosaccharides (galactose, fucose, GalNAc) used to inhibit vWF clearance receptor interaction while administering exogenous vWF.
• The claim set spans plasma-derived and recombinant vWF and covers receptor families broadly through claim 1, then narrows via dependent claims 7-10.
• Claim 3 adds evidentiary tightness by requiring a link to increased factor VIII AUC, creating a potential dispute point even if claim 1 is read.
• Competitive risk is highest for programs that co-administer these specific monosaccharides with vWF to extend half-life, and for regimens that can be framed as inhibiting vWF clearance receptor interactions in the hemophilia A/VWD setting.
• Design-around is most plausible through changing sugar structure (modification or moving beyond monosaccharides) or using a non-receptor-interaction-blocking approach.

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FAQs

1) Does US 9,707,269 cover both plasma-derived and recombinant vWF?
Yes. Dependent claims 4 and 5 explicitly cover plasma-derived and recombinant exogenous vWF.

2) Can a competitor avoid claim 6 by dosing the sugar at the same time as vWF?
Claim 6 requires “prior to” administration. Timing could be a factor for claim 6, but claim 1 is broader and does not require pre-dosing.

3) If a product uses fucose but not derived from ABO(H) antigen, is it still within the claim?
Claim 1 requires the isolated monosaccharide be an “accessible sugar residue derived from ABO(H) blood group antigen,” so derivation and sourcing could be a construal issue.

4) Are receptor-specific dependent claims mandatory to prove infringement?
No. They are dependent on claim 1, so infringement can be pursued under claim 1 without meeting the receptor-specific limitations, while dependent claims provide additional hooks.

5) How do factor VIII AUC requirements affect enforcement of claim 3?
Claim 3 requires that reduced vWF clearance leads to a concomitant increase in factor VIII AUC, creating a measurable causal/evidentiary element beyond claim 1’s half-life focus.

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References (APA)

1. US Patent 9,707,269.

Details for Patent 9,707,269

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	VONVENDI	von willebrand factor (recombinant)	For Injection	125577	8-Dec-15	9,707,269	2033-03-15