Patent: 10,245,348

Summary for Patent: 10,245,348

Title:	Process for making dry and stable hemostatic compositions
Abstract:	Described is a process for making a dry and stable hemostatic composition, said process comprising a) providing a first component comprising a dry preparation of a coagulation inducing agent, b) providing a second component comprising a dry preparation of a biocompatible polymer suitable for use in hemostasis, c) providing said first component and said second component in a combined form in a final container, c1) either by filling said first component and said second component into said final container so as to obtain a dry mixture in said final container, c2) or by providing said first component or said second component in said final container and adding said second component or said first component so as to obtain a combination of said first component with said second component in said final container, d) finishing the final container to a storable pharmaceutical device containing said first component and said second component in a combined form as a dry and stable hemostatic composition.
Inventor(s):	Goessl; Andreas (Vienna, AT), Osawa; Atsushi Edward (San Francisco, CA), Reich; Cary J. (Los Gatos, CA)
Assignee:	Baxter International Inc. (Deerfield, IL) Baxter Healthcare SA (Glattpark (Opfikon), CH)
Application Number:	14/804,084
Patent Claims:	see list of patent claims

United States Patent 10,245,348 (Claims 1-22): What the Patent Actually Covers and Where It Sits in the US Hemostat Dry-Formulation Landscape

What does US 10,245,348 claim, in operational terms?

US 10,245,348 claims a process for making a dry and stable hemostatic composition built around a lyophilized thrombin that is compacted and then combined inside the same container with a dry biocompatible polymer suitable for hemostasis. It ends with “finishing the container” into a storable pharmaceutical device.

Core independent claim (Claim 1)

Claim 1 is structurally a container-based manufacturing sequence:

1. Lyophilize an aqueous preparation of thrombin in a container to form:
   • First component: dry preparation of thrombin in-container
2. Compact the first component in the container after lyophilization
3. Add a second component after lyophilization:
   • Second component: dry preparation of a biocompatible polymer suitable for hemostasis
4. Mix first and second components in-container to obtain:
   • a dry mixture of thrombin + polymer in the container
5. Finish the container to create a storable pharmaceutical device containing the combined dry components

Claim 1 also implicitly ties the product outcome to the process: the device contains the two dry components in combined form and is storable.

Claim 2-22: scope expansions

The dependent claims narrow or broaden by specifying implementation details:

• Container form (Claim 2, 22): syringe, vial, tube; and specifically “container is one syringe” (Claim 22)
• Aseptic addition (Claim 3): adding second component under aseptic conditions
• Terminal sterilization method (Claim 4): ethylene oxide or ionizing irradiation
• Diluent-combination device (Claim 5): finished together with a diluent container for reconstitution
• Thrombin source (Claims 6-8): human, recombinant human, or bovine
• Polymer chemotypes (very broad) (Claims 9-12):
  • proteins (e.g., gelatin, soluble collagen, albumin, hemoglobin, fibrinogen, fibrin, casein, fibronectin, elastin, keratin, laminin)
  • polysaccharides (e.g., glycosaminoglycans, starch derivatives, cellulose derivatives, hemicellulose derivatives, xylan, agarose, alginate, chitosan)
  • polymer classes (e.g., polyacrylates, polymethacrylates, polyacrylamides, polyvinyl resins, polylactide-glycolides, polycaprolactones, polyoxyethylenes)
  • structural variants: crosslinked polysaccharide, crosslinked protein, crosslinked non-biologic polymer
• Physical form (Claim 13): particulate material
• Specific cross-linked gelatin (Claim 14)
• Radiation/EO sterilization stabilization (Claim 15):
  • stabilizer to inhibit polymer modification when exposed to sterilizing radiation
  • selected from ascorbic acid / sodium ascorbate / other ascorbate salts / antioxidant
• Delivery method (Claim 16): deliver hemostatic composition produced by Claim 1 to target site
• Reconstitution to hydrogel (Claim 17): contact with diluent to obtain hydrogel form
• Layering/granular assembly (Claim 18):
  • polymer in granular form
  • second component added by filling polymer “on top of” lyophilized thrombin
• Vacuum compaction (Claim 19): compact first component under vacuum
• Layering after compaction (Claim 20): fill granular polymer on top of compacted thrombin
• Second compaction step (Claim 21): compact second component after adding

Practical claim “center of gravity”

Across Claim 1 and its dependents, the novelty focus is not merely “dry thrombin + polymer.” It is the in-container, in-process assembly: lyophilize thrombin in the container, compact it, add a dry polymer after lyophilization, mix in-container, and finish into a storable device (often with diluent).

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What specific technical elements are claimed (and which are likely to drive patentability)?

The claim set contains multiple axes that will control novelty and enforceability.

A. In-container lyophilization + post-lyophilization mechanical compaction

• Lyophilization occurs in the container
• After lyophilization, the thrombin cake is compacted
• Compaction can be under vacuum (Claim 19)
• Compaction may extend to the polymer after addition (Claim 21)

This is a manufacturing workflow that competitors can avoid by using:

• separate lyophilized components removed and remixed outside the container, or
• no compaction step,
• or packaging formats that do not support the claimed sequence.

B. Dry polymer as the second component, added after lyophilization

Claim 1 requires:

• Second component is dry and is added after lyophilization
• mixing occurs in-container as a dry mixture

This can be a key differentiator versus systems that:

• blend thrombin with polymer while thrombin is still aqueous,
• lyophilize the combined formulation together (co-lyophilization),
• or formulate as wet admixture requiring immediate use.

C. Broad polymer identity but constrained by “suitable for hemostasis”

Claim 9-12 cast a wide net across:

• protein and polysaccharide classes,
• synthetic polymers,
• crosslinked forms.

Enforcement will likely turn on whether the defendant’s polymer is used “suitable for hemostasis” in the claimed device. That phrase can be argued as a functional limitation tied to use in hemostasis.

D. Sterilization compatibility and stabilizer (radiation modification inhibitor)

Claim 15 adds a crystallized technical limitation:

• if polymer modification under sterilizing radiation is inhibited,
• stabilizer is ascorbic acid/ascorbate salt/antioxidant.

This provides a narrower foothold for validity and infringement where sterilization is part of the claimed manufacturing route.

E. Device integration: diluent container and hydrogel reconstitution

Claims 5 and 17 tie the finished device to a delivery and reconstitution pathway:

• container is finished with a diluent container
• upon contacting the dry components with diluent, the composition forms a hydrogel

This can distinguish against dry powders intended for direct topical placement without hydrogel transformation.

F. Container types and aseptic addition

• syringe/vial/tube (Claims 2, 22)
• aseptic adding (Claim 3)

These are narrow but can matter for procedural infringement.

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Where does this patent sit in the US hemostatic dry thrombin / polymer device landscape?

The claim theme aligns with a known commercial and academic problem: thrombin stability and controlled formation of a hemostatic matrix after reconstitution. Multiple hemostatic products in the US market use thrombin and absorbable polymers or gels, including gelatin-based and polysaccharide-based systems. The critical distinction is the dry assembly method and in-container workflow.

Landscape interpretation (from the claims alone)

Even without looking at prosecution history, the claim structure suggests the patent aims to cover:

• a two-component kit built around lyophilized thrombin plus a dry polymer particulate/granular filler,
• combined in the delivery container (syringe or similar) to produce a storable hemostatic device,
• then reconstituted to hydrogel at the point of use.

In practice, this is positioned against three main competitor architectures:

1. Co-lyophilized thrombin+polymer where both components are dried together.
   • Avoids the “add second component after lyophilizing thrombin” structure.
2. Wet blending then lyophilization of a mixture.
   • Avoids the “dry second component added after lyophilization” limitation.
3. External reconstitution (separate mixing steps, mixers, or pre-made gels).
   • Avoids “mix in the container” and “finish container as storable pharmaceutical device containing combined form.”

This patent is most exposed where the competitor’s process does not preserve the same ordering and in-container combination steps.

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How strong are the claims as enforcement tools?

1) Claim 1 is broad on polymer identity but narrow on process ordering

• Broad: the polymer family is extensive (proteins, polysaccharides, synthetic polymers, crosslinked variants).
• Narrow: the manufacturing steps are tightly ordered (lyophilize thrombin in-container, compact, add dry polymer after lyophilization, mix in-container, finish as storable device).

That combination creates both opportunities and vulnerabilities:

• Many competitors may use thrombin + biopolymer hemostats, but fewer replicate this exact post-lyophilization in-container dry combining workflow.
• Validity risk rises if prior art discloses essentially the same process sequence with any hemostatic polymer falling within the broad genus.

2) Dependent claims add manufacturing and sterilization specifics

Claims 3-4-15 add “aseptic,” “EO or ionizing,” and “ascorbate/antioxidant stabilizer” constraints. These can strengthen enforceability for manufacturers that follow those exact controls, but they reduce coverage for those who sterilize differently or omit specified stabilizers.

3) Claims 16-17 add downstream delivery/reconstitution, but they depend on Claim 1

• If Claim 1 is designed around a patentable process, Claim 16 and 17 inherit that dependency.
• Competitors can sometimes design around by using a different process even if their end-product behavior (hydrogel formation at use) is similar.

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Claim-by-claim criticality: what to watch for in prior art and design-arounds

Most infringement-sensitive

• Claim 1 ordering: lyophilize thrombin in container → compact → add dry polymer after lyophilization → mix → finish
• In-container mixing and “storable pharmaceutical device containing combined form”
• Dry polymer second component added after lyophilization

Most validity-sensitive (prior art likely)

• In-container lyophilization and post-lyophilization handling of thrombin
• Use of biocompatible polymers (especially gelatin/collagen/chitosan/alginate) as hemostats
• Sterilization via ethylene oxide or ionizing radiation and use of antioxidants/ascorbate stabilizers

Because Claim 9-12 are so broad, prior art that discloses any reasonable polymer genus used with thrombin in a similar dry device process can threaten novelty if it also discloses the process sequence.

Easiest design-arounds

• Avoid “compacting the first component”
• Avoid “adding second component after lyophilizing step”
• Avoid “mixing ... in the container” (mix outside the container or using a different container architecture)
• Use co-lyophilization of thrombin with polymer
• Use different sterilization method without the claimed stabilizer linkage (or avoid EO/ionizing route altogether)

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What does the claim set imply about the intended device class (commercial mapping)?

Device architecture likely captured

• Syringe or vial containing:
  • a dry thrombin cake,
  • a dry granular polymer component added atop/over the thrombin cake,
  • then mixing and reconstitution to hydrogel at use.
• Often a dual-container system: device + separate diluent container.

Functional outcome

• Dry and stable until use
• Hydrogel formation after diluent contact
• Hemostasis delivery to a target site

This points to a line of product concepts that rely on stability during storage and rapid formation of a matrix at application.

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Patent landscape risks and leverage points for investors/R&D

Risks

• Overbreadth on polymer identity: Claim 9-12 are broad genus terms. Prior art that discloses a similar in-container dry thrombin with a hemostatic polymer likely threatens validity if the process ordering is the same.
• Process claims are fact-intensive: proving infringement requires evidence of manufacturing steps (in-container lyophilization, compaction, post-lyophilization dry addition, in-container mixing, finishing into a storable device).

Leverage

• Clear procedural ordering creates enforceable hooks: competitors who keep process steps distinct (co-lyophilize, wet blend, or mix outside container) can reduce risk.
• Sterilization stabilization (Claim 15) and specific compaction conditions (Claim 19) can provide narrower but more provable infringement anchors.

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Key Takeaways

• US 10,245,348 claims an in-container, in-process assembly: lyophilized thrombin is compacted, then a dry hemostatic polymer is added and mixed in the same container, then the container is finished as a storable pharmaceutical device; reconstitution to a hydrogel is contemplated via dependent claims.
• The claims are broad on polymer selection but narrow on manufacturing sequence. That profile favors enforcement against manufacturers who match the ordering and in-container mixing workflow.
• The most effective design-arounds are to change the process ordering or the assembly mechanics: co-lyophilize, omit compaction, or mix outside the container.
• Sterilization-related dependents (EO/ionizing; ascorbate/antioxidant stabilizer) can strengthen infringement where a competitor uses that exact sterilization and stabilization scheme.

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FAQs

1) What is the single most important limitation in Claim 1?

The ordering and in-container sequence: lyophilize thrombin in the container, compact it, add a dry polymer component after lyophilization, then mix in the container to form a storable combined dry device.

2) Does Claim 1 require any specific polymer chemistry?

No. It broadly covers many hemostatic biocompatible polymers, including proteins, polysaccharides, synthetic polymer classes, and crosslinked variants, as long as they are “suitable for use in hemostasis.”

3) Can a competitor avoid infringement by co-lyophilizing thrombin with the polymer?

Yes, co-lyophilization changes the process ordering and can avoid the “adding the second component following the lyophilizing step” requirement.

4) What dependent claims add the tightest manufacturing specificity?

Claim 3 (aseptic addition), Claim 4 (EO or ionizing sterilization), Claim 15 (ascorbate/antioxidant stabilizer under radiation), Claim 19 (vacuum compaction), and Claim 18/20 (granular layering on top).

5) What downstream use does the patent cover?

It covers delivering the device’s hemostatic composition to a target site (Claim 16) and reconstituting to a hydrogel using a pharmaceutically acceptable diluent (Claim 17).

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References

1. United States Patent No. 10,245,348. “Process for Making Dry and Stable Hemostatic Compositions and Devices.” (Claims 1-22 as provided in the prompt).

Details for Patent 10,245,348

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Omrix Biopharmaceuticals Ltd	EVITHROM	thrombin, topical (human)	Solution	125247	August 27, 2007	10,245,348	2035-07-20
Omrix Biopharmaceuticals Ltd	EVITHROM	thrombin, topical (human)	For Injection	125247	September 17, 2009	10,245,348	2035-07-20