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Executive summary: US Patent 4,160,025 covers a manufacturing process and resulting Factor VIII inhibitor bypassing activity (“FEIBA”) preparation built from plasma containing Factors II, VII, IX and X processed with water-insoluble inorganic surface-active adsorbents (diatomaceous earths; silicon dioxide/aluminum oxide substances) in the absence of free calcium ions, followed by basic ion-exchange adsorption, elution, and concentration. Dependent claims narrow to process windows (pH 5.5-8.5; 0-30°C), adsorbent load, specific starting plasma types, a DEAE-containing high-molecular-weight ion exchanger, and specific adsorbents (Celite, kaolin). Further dependents tightly constrain product quality/ratio parameters (FEIBA unit normalization; FEIBA-to-II/VII/IX/X ratio; amidolytic activity limits; thrombin-to-FEIBA activity cap). From a landscape perspective, the claim set is broad at the level of conceptual process architecture and inorganic adsorbent/ion-exchange framework, but it becomes increasingly vulnerable on infringement if a competitor uses different calcium handling, different adsorbent chemistry/material class, a different capture/adsorption mechanism, different ion-exchange functionality, or avoids the claimed activity/impurity ratio specifications.

What does US Patent 4,160,025 claim about FEIBA manufacturing (and what is the core invention)?

Core claim theme (independent claim 1): a method to produce a blood-coagulation promoting preparation with Factor VIII inhibitor bypassing activity by processing plasma containing Factors II, VII, IX and X with a calcium-free, coagulation-inhibiting adsorbent system, then purifying/enriching using basic ion exchange.

Claim 1 technical steps (element-by-element)

Starting material: “plasma containing coagulation Factors II, VII, IX and X.”
Calcium condition: “in the absence of free calcium ions” to keep the plasma “non-coagulating when treated with” the surface-active adsorbent.
Inorganic adsorbent / surface-active step: treat with “water-insoluble inorganic coagulation-physiologically-surface-active substance” selected from:
- diatomaceous earths, or
- substances composed of silicon dioxide and aluminum oxide. This step “generate[s] the Factor VIII inhibitor bypassing active (FEIBA) substance.”
Solid-liquid separation: separate the water-insoluble substances.
Capture/purification: treat the supernatant with a basic ion exchanger to adsorb:
- the FEIBA substance, and
- coagulation Factors II, VII, IX and X.
Elution: elute FEIBA and the coagulation factors from the basic ion exchanger.
Final conditioning: concentrate FEIBA and the coagulation factors.

Claim 9 mirrors the composition claim

Independent claim 9 is a preparation claim defined by the same manufacturing recipe and includes:

effective amount of FEIBA activity, and
a FEIBA substance produced by the same calcium-free inorganic surface-active treatment + basic ion-exchange adsorption/elution + concentration.

Practical implication: claim coverage is not only about what the FEIBA product is, but also about how it is produced and, in downstream claims, about activity normalization and impurity/ratio constraints.

Which aspects of claim 1 determine infringement risk for FEIBA competitors?

Infringement depends on whether an accused process matches each materially limiting feature. The biggest “forks” for design-around are listed below.

1) “Absence of free calcium ions” and non-coagulating behavior

Claim 1 requires that the plasma be treated without free calcium ions and that it is non-coagulating when treated with the selected surface-active substances.
Design-around vector: alternative calcium management (e.g., bound calcium, different chelation strategy, or calcium-free but not matching “non-coagulating when treated” conditions) can create a non-literal mismatch if “free calcium ions” or “non-coagulating when treated” is not satisfied.

2) Adsorbent material class is constrained to specific inorganic surface-active systems

Claim 1 limits adsorbents to:

diatomaceous earths; and
silicon dioxide/aluminum oxide substances.

Design-around vector: competitors using different inorganic adsorbents (different oxides, different composite materials, polymeric adsorption media, membrane separation, affinity capture) can argue non-infringement.

3) The FEIBA-forming step must be tied to that adsorbent treatment

The claim states the FEIBA substance is “generated” during treatment with the claimed inorganic surface-active substance.

Design-around vector: if FEIBA activity is generated primarily via other steps (e.g., enzyme-mediated modification, different fractionation, or a different adsorption matrix) then the “generated by treating…” element is harder to meet.

4) Basic ion exchanger as the capture/purification mechanism

Claim 1 requires treating the supernatant with a basic ion exchanger to adsorb both FEIBA activity and Factors II/VII/IX/X, then eluting them.

Design-around vector: use of non-ion-exchange separation (e.g., ultrafiltration + precipitation, chromatographic modalities without ion-exchange functionality) or ion exchangers that do not qualify as “basic” can reduce literal fit.

How do dependent claims narrow the patent: process parameters, plasma sources, and specific adsorbents?

Dependent claims 2-8 reduce scope and create additional “must-match” limitations.

Claim 2: temperature and pH window

pH: 5.5 to 8.5
temperature: 0°C to 30°C
If a competitor operates outside these windows, they can narrow defenses to dependent claim coverage (though not claim 1 if independent claim 1 still matches).

Claim 3 and 4: adsorbent dosage ranges

Claim 3: 0.05% to 5% adsorbent based on plasma amount
Claim 4: 0.1% to 1% adsorbent based on plasma amount
These are important for manufacturing consistency. A competitor using substantially higher/lower doses can avoid these dependents.

Claim 5: allowed plasma types

citrated plasma
cryosupernatant of frozen plasma
plasma supernatant of Cohn’s precipitate I

If a competitor uses different plasma fractions (or different sourcing such as recovered plasma, reconstituted fractions, or different manufacturing streams), dependent claim 5 becomes harder to meet.

Claim 6: ion exchanger specification (DEAE-like)

“basic ion exchanger” is a high molecular weight substance containing diethylaminoethyl groups. This is a key narrowing. If the capture step uses a different ion exchanger chemistry (or different functional group density), it may not fall within the dependent claim 6.

Claims 7 and 8: specific inorganic adsorbents

Claim 7: celite
Claim 8: kaolin These are narrower material embodiments under the broader “diatomaceous earths” and “silicon dioxide/aluminum oxide” umbrellas.

What product quality limitations are claimed in US 4,160,025 (FEIBA units, activity ratios, amidolytic activity, thrombin-to-FEIBA impurity controls)?

Claims 10-14 tightly define FEIBA preparations using functional assays and activity ratios, which can drive both infringement and validity scrutiny in practice.

Claim 10: FEIBA-to-Factors II/VII/IX/X ratio bounds

Ratio is expressed as:
- one unit of coagulation factors II-VII-IX-X = activity contained on average in 1 mL fresh human citrated plasma
- one FEIBA-unit = FEIBA activity that reduces activated partial thromboplastin time (aPTT) of a high-titer factor VIII inhibitor plasma to half of the blank value
Ratio between 0.1 and 10 This claim covers balance between FEIBA potency and factor content.

Claim 11: narrower ratio

Ratio between 0.5 and 2

Claim 12 and 13: amidolytic activity limits tied to specific chromogenic substrates

Claims 12-13 restrict “specific amidolytic activity” measured with:

N-benzoyl-L-phenylalanyl-L-valyl-L-arginine-p-nitroanilide.HCl
N-benzoyl-L-isoleucyl-L-glutamyl-L-glycyl-L-arginyl-p-nitroanilide.HCl
D-valyl-L-leucyl-L-lysyl-p-nitroanilide.2HCl

Limits:

Claim 12:
- ΔOD (10^3/min) per 1 FEIBA-unit ≤ 4
- ΔOD (10^3/min) per 1 unit of Factors II-VII-IX-X activity ≤ 3
Claim 13:
- ΔOD (10^3/min) per 1 FEIBA-unit < 3
- ΔOD (10^3/min) per 1 unit of Factors II-VII-IX-X activity < 2

Why it matters commercially: these parameters can act as a proxy for residual protease activity, thrombin-related impurities, or other enzymatic species that would otherwise broaden clinical or regulatory risk.

Claim 14: thrombin-to-FEIB activity cap

Ratio of thrombin activity to FEIB-activity does not exceed 0.02
Thrombin activity in NIH units
FEIB activity in FEIBA units

Infringement note: if a competitor produces FEIBA with thrombin activity above that threshold (or uses different impurity characterization), dependent claim 14 may not be met even if the process matches claim 1.

Does claim 15 expand coverage beyond manufacturing into administration to inhibitor-to-Factor VIII patients?

Claim 15 is a method-of-treatment claim:

Administer to a patient having blood with a Factor VIII inhibitor an amount effective to provide Factor VIII inhibitor bypassing activity of FEIBA produced by the same process steps as claim 1.

Key coverage attributes

Ties therapeutic effect directly to FEIBA produced by the claimed manufacturing steps.
Captures clinical use in inhibitor-to-Factor VIII populations.

Design-around vector

A competitor using an otherwise similar FEIBA that differs in claimed manufacturing steps can argue against both product and method-of-use claim coverage.
Changes in dosage regimen that still “provide Factor VIII inhibitor bypassing activity” can be harder to design around if the active ingredient concept is broad.

How strong is the patent estate coverage conceptually: broad process architecture vs narrow embodiments?

US 4,160,025 is strongest where accused products/processes match the patent’s “mechanistic scaffold”:

calcium-free plasma,
inorganic surface-active adsorbent (diatomaceous earth or SiO2/Al2O3),
basic ion exchange capture of both FEIBA and II/VII/IX/X,
defined activity/impurity ratios in dependent claims.

Where the claim set is relatively narrow (and vulnerability increases)

Dependent claims 6-8 (DEAE high molecular weight exchanger; celite; kaolin) and claims 2-4 (exact pH/temp/dose ranges) narrow coverage.
Claims 10-14 rely on specific functional unit definitions and specific chromogenic amidolytic assays and thrombin activity ratio. If a competitor’s release specs are different (even with functionally similar product), they may evade dependents.

What FEIBA “generic entry” risks does this patent create (even without mapping to other listed patents)?

Even without a full Orange Book cross-reference, the claim architecture indicates typical entry risk patterns for FXI inhibitor bypassing products and FEIBA-like preparations:

Risk drivers

If a generic applicant attempts to manufacture by the same inorganic adsorption + basic ion exchange workflow, claim 1 and claim 9 are the primary infringement targets.
If a generic applicant uses different capture chemistry (not basic ion exchange) or a different adsorbent material class, risk shifts downward.

The “testing specification” risk

Dependent claims 10-14 can create additional product-level infringement exposure if a generic or biosimilar-like product releases with:

the same FEIBA/factor unit ratio bounds, and
amidolytic activity and thrombin ratio thresholds.

Litigation posture implied by claim structure

Because claim 1 is process-defined and includes relatively specific chemistry-material constraints, enforcement often focuses on:

documented manufacturing conditions (calcium handling; pH/temp; adsorbent identity and dosage),
chromatography/adsorption media characterization (basic ion exchanger; DEAE-like groups),
release assay data (amidolytic substrate panels; thrombin/NHI unit measurement; FEIBA unit definition; aPTT assay outcome).

How does US 4,160,025 compare with common FEIBA process design choices (where it lines up vs where it diverges)?

Line-up with typical FEIBA-like fractionation:

adsorption-based concentration of clotting-factor complexes,
ion-exchange polishing,
limiting activation/impurities using calcium control.

Potential divergences by design:

replacement of the specified inorganic adsorbents,
membrane-based concentration without claimed basic ion exchange,
different ion exchanger functionality (not “basic” or not diethylaminoethyl-containing),
different product activity ratios and impurity profiles that do not meet dependent claim thresholds.

Key takeaways

Independent coverage (claims 1 and 9) is anchored on a defined manufacturing scaffold: calcium-free plasma + specified inorganic surface-active adsorbents + basic ion exchange adsorption/elution + concentration to produce FEIBA activity.
Dependent claims (2-8) narrow to operational parameters (pH/temp/adsorbent load), starting plasma sources, specific adsorbents (celite/kaolin), and an ion exchanger with diethylaminoethyl groups.
Dependent claims (10-14) narrow further by assay-defined product specifications: FEIBA unit ratio bounds, chromogenic amidolytic activity limits, and a thrombin-to-FEIBA ratio cap.
Method-of-use claim (15) expands to administration to Factor VIII inhibitor patients, but still depends on FEIBA being produced by the claimed process.
The strongest infringement exposure comes from manufacturers matching both the chemistry-material steps and the functional release/specification profile embedded in the dependent claims.

FAQs

1) What is the single most important limitation in claim 1 for process infringement?

The combination of (i) plasma treated without free calcium ions and (ii) treated with the specified inorganic surface-active adsorbents to generate FEIBA, followed by basic ion exchange adsorption of both FEIBA and Factors II/VII/IX/X.

2) Do the pH and temperature ranges in claim 2 affect only dependent-claim coverage?

Yes. Claim 2 limits coverage of that dependent claim; claim 1 can still be asserted if a process matches the independent elements.

3) Can a competitor avoid claim coverage by changing the adsorbent from diatomaceous earth to an alternative inorganic?

If the alternative is not within “diatomaceous earths” or “silicon dioxide and aluminum oxide” substances, it can break literal coverage for claim 1 and claim 9.

4) What do the amidolytic activity limits in claims 12-13 control in practice?

They function as release/specification constraints tied to specific chromogenic substrates and normalized to FEIBA unit and Factors II-VII-IX-X units, limiting enzymatic activity levels in the final FEIBA preparation.

5) Does claim 15 create exposure for prescribing even if manufacturing differs?

Claim 15 requires FEIBA to be “produced by” the claimed manufacturing sequence. If manufacturing does not match, it reduces the claim’s applicability.

References

United States Patent 4,160,025. (n.d.). Method for producing a blood-coagulation promoting preparation having factor VIII inhibitor bypassing activity (claims provided in prompt).

Title:	Method of producing a blood-coagulation-promoting preparation from human blood plasma
Abstract:	In a method of producing a blood-coagulation-promoting preparation from human blood plasma, which preparation contains a new blood-coagulating substance called \"FEIBA\", human plasma with citrate ions is treated with water-insoluble inorganic coagulation-physiologically-surface-active substances in the absence of free calcium ions, thus generating \"FEIBA\", the water-insoluble substances are separated, the supernatant is treated with basic ion exchangers, wherein \"FEIBA\" and the coagulation factors II-VII-IX-X adhere to the ion exchangers, and \"FEIBA\" and the factors II-VII-IX-X are eluted and concentrated.
Inventor(s):	Eibl; Johann (Vienna, AT), Schwarz; Otto (Vienna, AT), Elsinger; Fritz (Vienna, AT)
Assignee:	Immuno Aktiengesellschaft fur chemisch-medizinische Produkte (Vienna, AT)
Application Number:	05/822,679
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	Executive summary: US Patent 4,160,025 covers a manufacturing process and resulting Factor VIII inhibitor bypassing activity (“FEIBA”) preparation built from plasma containing Factors II, VII, IX and X processed with water-insoluble inorganic surface-active adsorbents (diatomaceous earths; silicon dioxide/aluminum oxide substances) in the absence of free calcium ions, followed by basic ion-exchange adsorption, elution, and concentration. Dependent claims narrow to process windows (pH 5.5-8.5; 0-30°C), adsorbent load, specific starting plasma types, a DEAE-containing high-molecular-weight ion exchanger, and specific adsorbents (Celite, kaolin). Further dependents tightly constrain product quality/ratio parameters (FEIBA unit normalization; FEIBA-to-II/VII/IX/X ratio; amidolytic activity limits; thrombin-to-FEIBA activity cap). From a landscape perspective, the claim set is broad at the level of conceptual process architecture and inorganic adsorbent/ion-exchange framework, but it becomes increasingly vulnerable on infringement if a competitor uses different calcium handling, different adsorbent chemistry/material class, a different capture/adsorption mechanism, different ion-exchange functionality, or avoids the claimed activity/impurity ratio specifications. What does US Patent 4,160,025 claim about FEIBA manufacturing (and what is the core invention)? Core claim theme (independent claim 1): a method to produce a blood-coagulation promoting preparation with Factor VIII inhibitor bypassing activity by processing plasma containing Factors II, VII, IX and X with a calcium-free, coagulation-inhibiting adsorbent system, then purifying/enriching using basic ion exchange. Claim 1 technical steps (element-by-element) Starting material: “plasma containing coagulation Factors II, VII, IX and X.” Calcium condition: “in the absence of free calcium ions” to keep the plasma “non-coagulating when treated with” the surface-active adsorbent. Inorganic adsorbent / surface-active step: treat with “water-insoluble inorganic coagulation-physiologically-surface-active substance” selected from: diatomaceous earths, or substances composed of silicon dioxide and aluminum oxide. This step “generate[s] the Factor VIII inhibitor bypassing active (FEIBA) substance.” Solid-liquid separation: separate the water-insoluble substances. Capture/purification: treat the supernatant with a basic ion exchanger to adsorb: the FEIBA substance, and coagulation Factors II, VII, IX and X. Elution: elute FEIBA and the coagulation factors from the basic ion exchanger. Final conditioning: concentrate FEIBA and the coagulation factors. Claim 9 mirrors the composition claim Independent claim 9 is a preparation claim defined by the same manufacturing recipe and includes: effective amount of FEIBA activity, and a FEIBA substance produced by the same calcium-free inorganic surface-active treatment + basic ion-exchange adsorption/elution + concentration. Practical implication: claim coverage is not only about what the FEIBA product is, but also about how it is produced and, in downstream claims, about activity normalization and impurity/ratio constraints. Which aspects of claim 1 determine infringement risk for FEIBA competitors? Infringement depends on whether an accused process matches each materially limiting feature. The biggest “forks” for design-around are listed below. 1) “Absence of free calcium ions” and non-coagulating behavior Claim 1 requires that the plasma be treated without free calcium ions and that it is non-coagulating when treated with the selected surface-active substances. Design-around vector: alternative calcium management (e.g., bound calcium, different chelation strategy, or calcium-free but not matching “non-coagulating when treated” conditions) can create a non-literal mismatch if “free calcium ions” or “non-coagulating when treated” is not satisfied. 2) Adsorbent material class is constrained to specific inorganic surface-active systems Claim 1 limits adsorbents to: diatomaceous earths; and silicon dioxide/aluminum oxide substances. Design-around vector: competitors using different inorganic adsorbents (different oxides, different composite materials, polymeric adsorption media, membrane separation, affinity capture) can argue non-infringement. 3) The FEIBA-forming step must be tied to that adsorbent treatment The claim states the FEIBA substance is “generated” during treatment with the claimed inorganic surface-active substance. Design-around vector: if FEIBA activity is generated primarily via other steps (e.g., enzyme-mediated modification, different fractionation, or a different adsorption matrix) then the “generated by treating…” element is harder to meet. 4) Basic ion exchanger as the capture/purification mechanism Claim 1 requires treating the supernatant with a basic ion exchanger to adsorb both FEIBA activity and Factors II/VII/IX/X, then eluting them. Design-around vector: use of non-ion-exchange separation (e.g., ultrafiltration + precipitation, chromatographic modalities without ion-exchange functionality) or ion exchangers that do not qualify as “basic” can reduce literal fit. How do dependent claims narrow the patent: process parameters, plasma sources, and specific adsorbents? Dependent claims 2-8 reduce scope and create additional “must-match” limitations. Claim 2: temperature and pH window pH: 5.5 to 8.5 temperature: 0°C to 30°C If a competitor operates outside these windows, they can narrow defenses to dependent claim coverage (though not claim 1 if independent claim 1 still matches). Claim 3 and 4: adsorbent dosage ranges Claim 3: 0.05% to 5% adsorbent based on plasma amount Claim 4: 0.1% to 1% adsorbent based on plasma amount These are important for manufacturing consistency. A competitor using substantially higher/lower doses can avoid these dependents. Claim 5: allowed plasma types citrated plasma cryosupernatant of frozen plasma plasma supernatant of Cohn’s precipitate I If a competitor uses different plasma fractions (or different sourcing such as recovered plasma, reconstituted fractions, or different manufacturing streams), dependent claim 5 becomes harder to meet. Claim 6: ion exchanger specification (DEAE-like) “basic ion exchanger” is a high molecular weight substance containing diethylaminoethyl groups. This is a key narrowing. If the capture step uses a different ion exchanger chemistry (or different functional group density), it may not fall within the dependent claim 6. Claims 7 and 8: specific inorganic adsorbents Claim 7: celite Claim 8: kaolin These are narrower material embodiments under the broader “diatomaceous earths” and “silicon dioxide/aluminum oxide” umbrellas. What product quality limitations are claimed in US 4,160,025 (FEIBA units, activity ratios, amidolytic activity, thrombin-to-FEIBA impurity controls)? Claims 10-14 tightly define FEIBA preparations using functional assays and activity ratios, which can drive both infringement and validity scrutiny in practice. Claim 10: FEIBA-to-Factors II/VII/IX/X ratio bounds Ratio is expressed as: one unit of coagulation factors II-VII-IX-X = activity contained on average in 1 mL fresh human citrated plasma one FEIBA-unit = FEIBA activity that reduces activated partial thromboplastin time (aPTT) of a high-titer factor VIII inhibitor plasma to half of the blank value Ratio between 0.1 and 10 This claim covers balance between FEIBA potency and factor content. Claim 11: narrower ratio Ratio between 0.5 and 2 Claim 12 and 13: amidolytic activity limits tied to specific chromogenic substrates Claims 12-13 restrict “specific amidolytic activity” measured with: N-benzoyl-L-phenylalanyl-L-valyl-L-arginine-p-nitroanilide.HCl N-benzoyl-L-isoleucyl-L-glutamyl-L-glycyl-L-arginyl-p-nitroanilide.HCl D-valyl-L-leucyl-L-lysyl-p-nitroanilide.2HCl Limits: Claim 12: ΔOD (10^3/min) per 1 FEIBA-unit ≤ 4 ΔOD (10^3/min) per 1 unit of Factors II-VII-IX-X activity ≤ 3 Claim 13: ΔOD (10^3/min) per 1 FEIBA-unit < 3 ΔOD (10^3/min) per 1 unit of Factors II-VII-IX-X activity < 2 Why it matters commercially: these parameters can act as a proxy for residual protease activity, thrombin-related impurities, or other enzymatic species that would otherwise broaden clinical or regulatory risk. Claim 14: thrombin-to-FEIB activity cap Ratio of thrombin activity to FEIB-activity does not exceed 0.02 Thrombin activity in NIH units FEIB activity in FEIBA units Infringement note: if a competitor produces FEIBA with thrombin activity above that threshold (or uses different impurity characterization), dependent claim 14 may not be met even if the process matches claim 1. Does claim 15 expand coverage beyond manufacturing into administration to inhibitor-to-Factor VIII patients? Claim 15 is a method-of-treatment claim: Administer to a patient having blood with a Factor VIII inhibitor an amount effective to provide Factor VIII inhibitor bypassing activity of FEIBA produced by the same process steps as claim 1. Key coverage attributes Ties therapeutic effect directly to FEIBA produced by the claimed manufacturing steps. Captures clinical use in inhibitor-to-Factor VIII populations. Design-around vector A competitor using an otherwise similar FEIBA that differs in claimed manufacturing steps can argue against both product and method-of-use claim coverage. Changes in dosage regimen that still “provide Factor VIII inhibitor bypassing activity” can be harder to design around if the active ingredient concept is broad. How strong is the patent estate coverage conceptually: broad process architecture vs narrow embodiments? US 4,160,025 is strongest where accused products/processes match the patent’s “mechanistic scaffold”: calcium-free plasma, inorganic surface-active adsorbent (diatomaceous earth or SiO2/Al2O3), basic ion exchange capture of both FEIBA and II/VII/IX/X, defined activity/impurity ratios in dependent claims. Where the claim set is relatively narrow (and vulnerability increases) Dependent claims 6-8 (DEAE high molecular weight exchanger; celite; kaolin) and claims 2-4 (exact pH/temp/dose ranges) narrow coverage. Claims 10-14 rely on specific functional unit definitions and specific chromogenic amidolytic assays and thrombin activity ratio. If a competitor’s release specs are different (even with functionally similar product), they may evade dependents. What FEIBA “generic entry” risks does this patent create (even without mapping to other listed patents)? Even without a full Orange Book cross-reference, the claim architecture indicates typical entry risk patterns for FXI inhibitor bypassing products and FEIBA-like preparations: Risk drivers If a generic applicant attempts to manufacture by the same inorganic adsorption + basic ion exchange workflow, claim 1 and claim 9 are the primary infringement targets. If a generic applicant uses different capture chemistry (not basic ion exchange) or a different adsorbent material class, risk shifts downward. The “testing specification” risk Dependent claims 10-14 can create additional product-level infringement exposure if a generic or biosimilar-like product releases with: the same FEIBA/factor unit ratio bounds, and amidolytic activity and thrombin ratio thresholds. Litigation posture implied by claim structure Because claim 1 is process-defined and includes relatively specific chemistry-material constraints, enforcement often focuses on: documented manufacturing conditions (calcium handling; pH/temp; adsorbent identity and dosage), chromatography/adsorption media characterization (basic ion exchanger; DEAE-like groups), release assay data (amidolytic substrate panels; thrombin/NHI unit measurement; FEIBA unit definition; aPTT assay outcome). How does US 4,160,025 compare with common FEIBA process design choices (where it lines up vs where it diverges)? Line-up with typical FEIBA-like fractionation: adsorption-based concentration of clotting-factor complexes, ion-exchange polishing, limiting activation/impurities using calcium control. Potential divergences by design: replacement of the specified inorganic adsorbents, membrane-based concentration without claimed basic ion exchange, different ion exchanger functionality (not “basic” or not diethylaminoethyl-containing), different product activity ratios and impurity profiles that do not meet dependent claim thresholds. Key takeaways Independent coverage (claims 1 and 9) is anchored on a defined manufacturing scaffold: calcium-free plasma + specified inorganic surface-active adsorbents + basic ion exchange adsorption/elution + concentration to produce FEIBA activity. Dependent claims (2-8) narrow to operational parameters (pH/temp/adsorbent load), starting plasma sources, specific adsorbents (celite/kaolin), and an ion exchanger with diethylaminoethyl groups. Dependent claims (10-14) narrow further by assay-defined product specifications: FEIBA unit ratio bounds, chromogenic amidolytic activity limits, and a thrombin-to-FEIBA ratio cap. Method-of-use claim (15) expands to administration to Factor VIII inhibitor patients, but still depends on FEIBA being produced by the claimed process. The strongest infringement exposure comes from manufacturers matching both the chemistry-material steps and the functional release/specification profile embedded in the dependent claims. FAQs 1) What is the single most important limitation in claim 1 for process infringement? The combination of (i) plasma treated without free calcium ions and (ii) treated with the specified inorganic surface-active adsorbents to generate FEIBA, followed by basic ion exchange adsorption of both FEIBA and Factors II/VII/IX/X. 2) Do the pH and temperature ranges in claim 2 affect only dependent-claim coverage? Yes. Claim 2 limits coverage of that dependent claim; claim 1 can still be asserted if a process matches the independent elements. 3) Can a competitor avoid claim coverage by changing the adsorbent from diatomaceous earth to an alternative inorganic? If the alternative is not within “diatomaceous earths” or “silicon dioxide and aluminum oxide” substances, it can break literal coverage for claim 1 and claim 9. 4) What do the amidolytic activity limits in claims 12-13 control in practice? They function as release/specification constraints tied to specific chromogenic substrates and normalized to FEIBA unit and Factors II-VII-IX-X units, limiting enzymatic activity levels in the final FEIBA preparation. 5) Does claim 15 create exposure for prescribing even if manufacturing differs? Claim 15 requires FEIBA to be “produced by” the claimed manufacturing sequence. If manufacturing does not match, it reduces the claim’s applicability. References United States Patent 4,160,025. (n.d.). Method for producing a blood-coagulation promoting preparation having factor VIII inhibitor bypassing activity (claims provided in prompt). More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	December 21, 1979	⤷ Start Trial	1997-08-08
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	July 31, 2000	⤷ Start Trial	1997-08-08
Takeda Pharmaceuticals U.s.a., Inc.	AUTOPLEX, FEIBA NF, FEIBA VH	anti-inhibitor coagulant complex	For Injection	101447	August 11, 2005	⤷ Start Trial	1997-08-08
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Summary for Patent: 4,160,025