United States Patent 4,450,103: Claims, Technical Scope, and US Landscape Pressure-Test
What does US 4,450,103 actually claim?
US Patent 4,450,103 claims process technology for producing and recovering unglycosylated human IFN-β (interferon beta), including two distinct but related claim groups:
1) Direct extraction from an aqueous intermediate (independent claim 1 and dependent variants)
- Starts with an aqueous medium containing unglycosylated human IFN-β
- Contacts that aqueous medium with an organic extractant defined by a general structural formula (R = hydrogen or methyl)
- Forms aqueous and organic phases
- Variants narrow solubilizer type (anionic surfactant) and operating conditions (ionic strength, phase-separation facilitation)
- Dependent claims specify 2-butanol as the extractant and include an isolation step (back-extraction/precipitation conceptually)
2) Recovery from fermentation/bioprocess material (independent claim 9 and downstream narrowing to E. coli)
- Uses cell disruption (explicitly pressure cycling in claim 13)
- Solubilizes unglycosylated IFN-β using a surfactant that forms an extractable complex
- Extracts the complex using the same organic extractant class (R = H or methyl)
- Isolates the IFN-β from the organic phase (with a specific precipitation route in dependent claims)
Claim set summary (what is and is not in scope)
| Claim cluster |
Key elements that define infringement-relevant scope |
Most specific narrowing terms |
| Claim 1 (extraction from aqueous medium) |
aqueous IFN-β intermediate + organic extractant of defined formula (R = H or methyl) + two-phase formation |
solubilizing agent is anionic surfactant; ionic strength range; extractant = 2-butanol; isolation from extractant |
| Claim 9 (recovery from transformed microorganism) |
disrupt cells → solubilize IFN-β into aqueous medium with extractable-complex-forming solubilizer → extract with organic extractant → isolate from extract |
bacterium/E. coli; concentration; pressure cycling; pH maintenance; SDS/Laurate specific ratios |
| Claim 29 (method locked to transformed E. coli workflow) |
fermentation concentration → pressure cycling → solid/liquid separation → suspend cells/disruptate at specified protein and pH → solubilize with SDS at defined ratio → extract with 2-butanol with immiscibility conditions → phase separation → precipitate by pH drop |
protein concentration 2–15 mg/mL, pH 7–8; SDS:protein 1:1 to 1:5; precipitation pH below 5; immiscibility by ionic strength |
What are the core technical “levers” that constrain the patent’s reach?
Across claim 1/9/29, the practical claim boundaries are controlled by four technical levers.
1) The target is specific: “unglycosylated human IFN-β”
This is not a generic interferon recovery. It requires the product form to be unglycosylated and human IFN-β.
2) Solubilizing agent must be anionic surfactant that forms an extractable complex
- Claim 2 requires “anionic surface active agent.”
- Claim 3 specifies sodium dodecyl sulfate (SDS) or sodium laurate.
- Claim 17 specifies anionic classes: “alkali metal alkyl sulfate” or “alkali metal salt of a fatty acid” with 10 to 14 carbons.
- Claims 20–21 and 28–29 lock SDS ratios.
Infringement impact: A competitor using a neutral solubilizer, cationic detergent, chaotrope, or different complexing mechanism is structurally outside the claim language.
3) Organic extractant is defined by formula (R = H or methyl) and is exemplified as 2-butanol
- Claim 7: extractant is 2-butanol.
- Claim 25 reiterates 2-butanol.
- Claim 29 locks extraction to 2-butanol and imposes immiscibility maintenance via ionic strength.
Infringement impact: The independent claims use a formula definition, but the written dependent claims strongly anchor commercial embodiments to 2-butanol. If an implementation uses a different alcohol (e.g., n-butanol, isopropanol, tert-butanol), the fight becomes claim construction around the formula definition plus “equivalents” (not stated here) and whether that alcohol matches the defined R substitution.
4) Aqueous ionic strength and pH ranges are explicit
- Claim 5: ionic strength 0.05 to 0.15
- Claim 6: sodium chloride provides the ionic strength
- Claim 19: pH 7 to 8
- Claim 15: pH maintains the surfactant in solution
- Claims 26–27 and 29: precipitation via pH below ~5
Infringement impact: A process that avoids those ionic strength bands or uses a pH profile that never crosses those thresholds can steer around dependent claim limitations, though it may still hit the broader independent claim if those conditions are not required in the independent claim.
How narrow is the independent claim scope vs dependent claim funneling?
Claim 1 (broadest in the “extraction from aqueous intermediate” group)
Claim 1 requires:
- Unglycosylated human IFN-β in aqueous medium
- Solubilized with an “appropriate solubilizing agent”
- Contact with organic extractant of defined formula (R = H or methyl)
- Formation of aqueous and organic phases
But claim 1 does not expressly limit:
- the solubilizing agent type in the text you provided (it later narrows in claims 2–3)
- exact ionic strength
- pH
- extractant being 2-butanol (that appears in claim 7)
So claim 1’s independent reach is “aqueous intermediate + specified organic extractant class + two-phase formation,” with solubilization presumed compatible.
Claim 9 (broadest in the “fermentation recovery” group)
Claim 9 requires:
- Microorganism transformed with unglycosylated human IFN-β
- Disrupt cell membrane
- Solubilize into aqueous medium with a solubilizing agent forming an extractable complex
- Extract with the defined organic extractant class
- Isolate unglycosylated IFN-β from the extract
Claim 9 also does not explicitly require:
- SDS vs other surfactants (that is dependent via claims 16–18)
- ionic strength range
- pressure cycling (claim 13)
- specific E. coli (claims 10–11)
This makes claim 9 potentially the most relevant “base” right to challenge or design around, because it covers alternative microbes and disruption methods so long as the complex-extract-isolate logic holds.
Claim 29 (tight “commercial embodiment” lock)
Claim 29 is the most constrained and reads like a process recipe:
- Transformed E. coli
- Concentrate bacteria in fermentation medium
- Pressure cycling disruption
- Separate solid cellular material
- Suspend cellular material in aqueous medium at 2 to 15 mg/mL protein and pH 7 to 8
- Solubilize with SDS at SDS:protein 1:1 to 1:5
- Extract with 2-butanol where aqueous/2-butanol immiscibility is maintained by ionic strength
- Separate phases
- Precipitate by mixing with aqueous buffer and lowering pH to below 5
If a manufacturer follows this architecture, it is the highest probability hit.
What does the landscape imply for competitive freedom to operate?
US 4,450,103 is an older, method-focused process patent anchored on:
- a specific product form (unglycosylated human IFN-β),
- a surfactant-based extractable complex in aqueous phase,
- an organic extraction using a defined alcohol class (exemplified as 2-butanol),
- and explicit control parameters (ionic strength, pH, detergent ratios, and precipitation conditions).
For a modern competitor, the landscape pressure is typically twofold:
1) Process substitution is constrained because multiple claim limitations are interlinked:
- If you keep SDS and 2-butanol but change ionic strength or pH windows, you may avoid dependent claims while still risking claim 9/1 if those conditions are not required in the independent claims.
- If you keep SDS but switch alcohol, you may avoid 2-butanol dependents, but independent claim 1/9 may still read if the alternative alcohol falls within the claimed structural formula for the extractant (R = H or methyl).
2) Product form matters: “unglycosylated human IFN-β” limits the claims to that specific biophysical identity. A competitor producing a different glycosylation state may avoid the literal claim set.
Which claim elements are most likely to be litigated?
Extractant definition (structural formula)
The extractant is defined by a formula with R = hydrogen or methyl. The patent also states 2-butanol in multiple dependents. Disputes tend to focus on whether an alternative extractant:
- matches the formula (R = H or methyl substitution pattern), and/or
- is considered “the same” under claim construction rules.
Surfactant complex formation
Claims 9 and 1 pivot on a solubilizer that “forms an extractable complex.” That phrase creates two litigation hooks:
- whether the process actually forms such a complex (technical proof)
- whether a different detergent chemistry still produces an extractable complex as claimed (mechanism and evidence)
Ionic strength and immiscibility control
- Claims 5–6 and 23–24 define ionic strength ranges and sodium chloride as a source.
- Claim 29 ties immiscibility of aqueous/2-butanol to ionic strength “sufficient to maintain substantially immiscible.”
That combination invites disputes over whether the operating window truly satisfies the patent’s quantitative boundaries.
Cell disruption method (pressure cycling)
- Claim 13 includes pressure cycling.
- Claim 29 also uses pressure cycling.
If a competitor uses sonication, enzymatic lysis, high-pressure homogenization (not labeled pressure cycling), or chemical lysis, they may avoid those dependents while remaining at risk under claim 9.
Freedom-to-operate mapping: how to think about design-arounds
This is a “claim requirement checklist” based on the provided claims. It shows the decision points that most directly affect whether a competitor process falls in or out.
A. Keep risk-high
High probability of overlap if a competitor:
- uses unglycosylated human IFN-β as product,
- uses anionic surfactant solubilization (SDS or C10–C14 alkyl sulfate or C10–C14 fatty acid salts),
- extracts the complex with an alcohol matching the claimed formula (2-butanol is specifically named),
- isolates IFN-β by precipitation after extraction with pH drop below ~5.
B. Moderate risk (avoidance targets dependents first)
Risk reduces if a competitor:
- uses a different solubilizer type (non-anionic surfactants or non-extractable-complex chemistry),
- avoids the explicit ionic strength range (0.05–0.15) and sodium chloride provision,
- avoids pH 7–8 staging (claim 19/29),
- avoids SDS:protein 1:1 to 1:5 (claim 20/21/29),
- uses a disruption method other than pressure cycling (claim 13/29).
C. Lower risk
Literal risk is reduced if a competitor:
- does not produce unglycosylated human IFN-β (glycosylated or otherwise modified form),
- does not create the surfactant extractable complex in aqueous,
- uses an extractant outside the claimed structural formula family and not labeled as “2-butanol,”
- uses a precipitation strategy not tied to pH drop below ~5 after extraction.
What is the patent’s “actionable” commercial footprint?
Claim 29 reads like a process that could be implemented at scale. If that process was adopted or imitated by later developers, it becomes the most actionable element for:
- licensing analysis,
- process engineering gating,
- and invalidity or design-around planning.
Key “recipe parameters” in claim 29:
- E. coli fermentation and concentration prior to disruption
- Pressure cycling disruption
- protein concentration 2–15 mg/mL
- pH 7–8 in aqueous suspension
- SDS:protein weight ratio 1:1 to 1:5
- extract with 2-butanol
- ionic strength sufficient to make phases “substantially immiscible”
- precipitate by mixing the 2-butanol phase with aqueous buffer and lowering to pH below 5
Those are the levers that can be benchmarked against actual manufacturing runs, SDS usage records, brine addition, and alcohol selection.
Key Takeaways
- US 4,450,103 claims surfactant-complex-based extraction of unglycosylated human IFN-β using a defined alcohol extractant class (with 2-butanol explicitly tied to multiple dependents).
- The independent process claim for fermentation recovery (claim 9) is broad on microorganism and disruption method but requires: disruption, aqueous solubilization with an extractable complex, alcohol extraction, and isolation from the extract.
- The enforceability risk peaks at the detailed “embodiment” claim (claim 29) with locked parameters: E. coli, pressure cycling, protein 2–15 mg/mL, pH 7–8, SDS:protein 1:1 to 1:5, 2-butanol, phase immiscibility by ionic strength, and precipitation by pH below 5.
- For R&D and process redesign, the highest-value design-around points are: (i) surfactant class and whether it forms an extractable complex, (ii) extractant identity relative to the claimed alcohol formula and 2-butanol dependents, and (iii) ionic strength/pH windows that are quantified in the claims.
FAQs
1) What product form is required by US 4,450,103?
The claims require unglycosylated human IFN-β, not generic interferon β or glycosylated forms.
2) Is 2-butanol required to infringe?
It is required in several dependent claims (notably claim 7, claim 25, and claim 29). Independent claims define an extractant by a structural formula (R = hydrogen or methyl), so infringement may still occur with other alcohols if they fall within that defined formula family.
3) What solubilizers are explicitly covered?
The claims expressly include anionic surface active agents, including SDS (sodium dodecyl sulfate) and sodium laurate, and broader alkali metal alkyl sulfates or fatty-acid salts with 10 to 14 carbons.
4) Which process parameters are most specific?
Claim 29 is the tightest: protein 2 to 15 mg/mL, pH about 7 to 8, SDS:protein 1:1 to 1:5, and precipitation pH below about 5, plus ionic strength sufficient for immiscibility.
5) How does the patent handle upstream bioprocessing?
It covers recovery from transformed microorganisms, including explicit narrowing to bacterium/E. coli, with pressure cycling named for disruption and concentration prior to disruption.
References
- U.S. Patent 4,450,103.
