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US 6,482,613 patent estate analysis: claims, claim scope, and U.S. enforceability for DNA encoding mature human leukocyte interferon (165-166 aa) with an ATG-start

US 6,482,613 centers on DNA constructs encoding mature human leukocyte interferon (165-166 amino acids) lacking the native presequence, with an ATG immediately upstream of the codon for the N-terminal amino acid. Dependent claims lock to multiple specific mature interferon amino-acid sequences (SEQ ID NOs 45–59) with N-terminal cysteine, plus downstream U.S. process claims for bacterial production (transformed bacterium and specific E. coli strains).

From a freedom-to-operate perspective, the claim set is narrow in the protein sequence (mature leukocyte interferon limited to ~165–166 aa) and in the coding design (ATG placed immediately before the N-terminal codon; explicit exclusion of any presequence). The primary risk for would-be manufacturers comes from “straight” nucleic-acid claims (claims 1–16) and bacterial expression embodiments (claims 17–22), not from later formulation, dosing, or device claims.

What is US Patent 6,482,613 about and what are the core claim elements?

What does claim 1 require, in practical design terms?

Claim 1 requires all of the following technical elements:

A DNA comprising a nucleotide sequence encoding a polypeptide of 165–166 amino acids.
The encoded polypeptide is mature human leukocyte interferon.
The polypeptide is “unaccompanied by any corresponding presequence or portion thereof.”
The nucleotide sequence includes an ATG immediately preceding the codon corresponding to the amino-terminal amino acid of the 165–166 aa mature interferon.

Enforcement-relevant construction: A builder of bacterial expression constructs can avoid literal “ATG immediately preceding” only by changing the start-codon context (for example, using non-ATG initiation strategies) or by placing any additional nucleotides in between in a way that prevents the ATG from being “immediately preceding” under a strict reading. The “unaccompanied by any corresponding presequence” limits the claim to designs that do not encode a signal peptide/presequence that corresponds to the native form.

What do dependent claims 2–16 add?

Claims 2–16 narrow claim 1 to specific mature interferon amino-acid sequences identified as SEQ ID NO:45–59, each with the condition that:

the N-terminal amino acid is cysteine.

This turns claim 1’s broad “mature leukocyte interferon (165–166 aa)” into a closed set of specific mature sequences.

What do claims 17–22 cover beyond the DNA?

Claims 17–19 are manufacturing process claims:

culturing a bacterium transformed with a replicable bacterial expression vehicle containing a claimed DNA,
where the vehicle expresses the mature interferon (165–166 aa; and for certain claims, using specific SEQ ID-linked DNA variants).

Claims 20–22 are product-by-transformation / organism claims:

a bacterium transformed with the claimed DNA,
narrowed to E. coli and then E. coli K-12 strain 294 in claims 21–22.

How strong is the patent estate for US 6,482,613 based on claim structure and likely claim scope?

Where claim strength typically concentrates

Strength generally concentrates in claim categories that are easier to show by documentation and sequence identity:

DNA encoding claims (1–16): sequence-based; infringement can turn on whether the defendant’s construct encodes the specified mature interferon and includes an ATG immediately upstream of the N-terminal codon.
Bacterial expression vehicle/process claims (17–22): enforceability is often tied to production records, plasmid maps, and sequence verification of expression constructs.

Where enforceability is likely more contested

Claim 1’s phrase “unaccompanied by any corresponding presequence or portion thereof” can generate interpretive disputes:

What is the “corresponding presequence” for each mature leukocyte interferon variant?
If a defendant uses a leaderless mature protein but includes translation-related elements (not a biologically “presequence”), the question is whether those elements are considered a “portion thereof” or merely upstream genetic context.

Still, because the claim is written as a protein-length and “no presequence” requirement, the constraint is not open-ended. A defendant would usually mitigate risk by using different protein processing, different construct architecture, or different mature sequence identities.

What patents (and claim components) in US 6,482,613 map to nucleic acid sequence and translation start design?

Key claim construction hotspots

“ATG immediately preceding the codon”
- This is a specific drafting choice that targets bacterial expression designs where translation initiates at an ATG right before the N-terminal amino acid codon.
- A design that inserts extra nucleotides between the ATG and the codon might aim to avoid “immediately preceding,” though practical bacterial translation typically depends on proximity.
“mature human leukocyte interferon (165–166 amino acids)”
- This anchors the claim to a size range that reduces the universe of interferon variants.
- It also helps distinguish mature interferons that are longer or shorter (including engineered forms with extra residues).
“unaccompanied by any corresponding presequence or portion thereof”
- This excludes constructs encoding signal peptides or prepro regions that are part of a native precursor architecture.
- It also creates an argument surface if a construct includes any processing-related region considered part of the “corresponding presequence.”

Practical infringement proof points

Gene/ORF sequencing to establish:
- the encoded polypeptide length (165–166),
- identity of the mature interferon sequence (SEQ ID NO mapping),
- and the presence and placement of ATG relative to the N-terminal codon.
For process/organism claims:
- transformed host strain identity (for claims 21–22),
- expression plasmid sequence (for claims 17–19),
- and confirmation the host expresses the mature protein without presequence.

Which mature leukocyte interferon sequences are locked into dependent claims (SEQ ID NO:45–59)?

Dependent claims 2–16 define multiple mature interferon amino-acid sequences (SEQ ID NOs 45–59) and fix the N-terminal amino acid as cysteine. The legal consequence is that infringement of claims 2–16 depends on whether a defendant’s mature product matches one of those defined sequences.

Claim coverage split:

Claim 1: broader sequence coverage limited by mature interferon identity + 165–166 aa + ATG upstream + no presequence.
Claims 2–16: narrower to specific enumerated sequences.

Commercial implication: If a competitor uses a mature interferon sequence not matching those SEQ IDs (even if still “mature leukocyte interferon”), they may avoid dependent-claim infringement and potentially weaken whether claim 1 still reads, depending on whether the competitor product still satisfies the “mature human leukocyte interferon” definition and the 165–166 aa requirement.

How do the bacterial production claims expand risk for generic or follow-on manufacturers?

What claims 17–19 cover

Claims 17–19 cover manufacturing by culturing transformed bacteria where the expression vehicle contains the claimed DNA.

Two layers of risk:

DNA-level risk: infringement is triggered by the DNA included in the vehicle.
Process-level risk: the act of culturing the transformed bacterium to express the mature interferon can infringe.

What claims 20–22 cover

Organism claims create additional pathways for enforcement:

If a manufacturer produces in-house using a transformed host, the host can fall within “a bacterium transformed with a DNA according to claims 1–16.”
Claim 22 escalates specificity to E. coli K-12 strain 294.

In litigation, organism claims often test whether the defendant’s product strain and construct match the transformation requirement. Strain identity can be a hard pin, but most commercial processes do not typically document “K-12 strain 294” specifically unless it is their exact maintained strain.

When does US 6,482,613 lose exclusivity, and what are key U.S. timeline constraints?

No timeline calculations can be produced from the claim text alone. A full exclusivity and expiration analysis requires at least the filing date, priority chain, and any PTA/TSA events. This information is not provided in the record supplied here.

What would a Paragraph IV or biosimilar-type challenge look like for this patent?

Small-molecule Paragraph IV context: likely not applicable directly

US 6,482,613 is a nucleic acid and bacterial expression patent. If the commercial product is interferon expressed in bacteria, the legal structure differs from classic small-molecule generic Paragraph IV practice.

Biologic/biosimilar analog: more likely

If the product is an interferon biologic, the main legal challenge route in practice is tied to biosimilar pathway and patent listing mechanics rather than classic ANDA Paragraph IV. Still, the technical claim categories here focus on construct and expression method, which are more likely to show up as enforceability anchors in a biologic’s patent landscape.

How does US 6,482,613 compare with competing interferon gene patents in typical claim strategies?

Common competitor strategies to avoid these claims

Different start architecture
- Use non-ATG initiation, engineered ribosome binding/start configurations, or alter upstream coding context such that no ATG is “immediately preceding” the N-terminal codon.
Encode a different precursor design
- Include a processing sequence that is not “unaccompanied by any corresponding presequence,” or use a precursor with a different presequence identity and processing route, avoiding the “no corresponding presequence” limitation.
Use different mature sequence identities
- Make mature interferon variants that do not match SEQ ID NO:45–59 and potentially don’t satisfy the claim-1 “mature human leukocyte interferon” identity constraint.
Expression in non-bacterial systems
- If claims are tightly tied to “culturing a bacterium transformed with…” then production in yeast or mammalian systems can be a literal-claim avoidance pathway, depending on how the claim language is enforced and whether broader dependent claims exist outside 6,482,613.

Where competitors may still be exposed

Even with different host systems, claims 1–16 (DNA claims) can still be triggered if the accused entity uses the same DNA constructs anywhere in the chain, subject to jurisdictional proof.

What is the Orange Book status of US 6,482,613?

Orange Book status cannot be determined from the claim text provided. Orange Book listings require the associated NDA and the patent-to-product mapping, which is not supplied.

Key litigation and settlement facts for US 6,482,613

No litigation docket, settlement terms, or enforcement events are provided in the record supplied here. A claims-and-patent landscape analysis without those facts cannot accurately state litigation impact.

Key Takeaways

US 6,482,613 is a sequence- and construct-focused patent targeting DNA encoding mature human leukocyte interferon (165–166 aa) that is not accompanied by a corresponding presequence, with a defining ATG immediately upstream of the N-terminal codon.
Dependent claims 2–16 narrow protection to enumerated mature interferon sequences (SEQ ID NO:45–59) with N-terminal cysteine.
Claims 17–22 extend the reach into bacterial expression: culturing transformed bacteria using a replicable expression vehicle containing the claimed DNA, plus organism claims including E. coli and E. coli K-12 strain 294.
The claim scope suggests the highest infringement risk for competitors is use of the same mature sequence designs and the same translation start architecture in bacterial expression constructs.
Expiration/exclusivity timing and Orange Book mapping cannot be determined from the supplied information.

FAQs

Does US 6,482,613 cover plasmids or only naked DNA sequences?
What design changes can avoid literal infringement of the “ATG immediately preceding” requirement?
If a manufacturer uses a different host (yeast or mammalian), are claims 17–19 still at risk?
How do SEQ ID NO:45–59 dependencies affect product-by-product infringement for interferon variants?
Can infringement be established without proof of actual expression if the DNA construct is used internally?

References

No cited sources are provided in the input, so no APA reference list can be generated.

Title:	Microbial production of mature human leukocyte interferons
Abstract:	Disclosed herein are methods and means of microbially producing, via recombinant DNA technology, mature human leukocyte interferons, useful in the treatment of viral and neoplastic diseases.
Inventor(s):	Goeddel; David V. (Burlingame, CA), Pestka; Sidney (North Caldwell, NJ)
Assignee:	Hoffmann-La Roche Inc. (Nutley, NJ) Genentech, Inc. (South San Francisco, CA)
Application Number:	07/145,002
Patent Claims:	see list of patent claims
Patent landscape, scope, and claims summary:	US 6,482,613 patent estate analysis: claims, claim scope, and U.S. enforceability for DNA encoding mature human leukocyte interferon (165-166 aa) with an ATG-start US 6,482,613 centers on DNA constructs encoding mature human leukocyte interferon (165-166 amino acids) lacking the native presequence, with an ATG immediately upstream of the codon for the N-terminal amino acid. Dependent claims lock to multiple specific mature interferon amino-acid sequences (SEQ ID NOs 45–59) with N-terminal cysteine, plus downstream U.S. process claims for bacterial production (transformed bacterium and specific E. coli strains). From a freedom-to-operate perspective, the claim set is narrow in the protein sequence (mature leukocyte interferon limited to ~165–166 aa) and in the coding design (ATG placed immediately before the N-terminal codon; explicit exclusion of any presequence). The primary risk for would-be manufacturers comes from “straight” nucleic-acid claims (claims 1–16) and bacterial expression embodiments (claims 17–22), not from later formulation, dosing, or device claims. What is US Patent 6,482,613 about and what are the core claim elements? What does claim 1 require, in practical design terms? Claim 1 requires all of the following technical elements: A DNA comprising a nucleotide sequence encoding a polypeptide of 165–166 amino acids. The encoded polypeptide is mature human leukocyte interferon. The polypeptide is “unaccompanied by any corresponding presequence or portion thereof.” The nucleotide sequence includes an ATG immediately preceding the codon corresponding to the amino-terminal amino acid of the 165–166 aa mature interferon. Enforcement-relevant construction: A builder of bacterial expression constructs can avoid literal “ATG immediately preceding” only by changing the start-codon context (for example, using non-ATG initiation strategies) or by placing any additional nucleotides in between in a way that prevents the ATG from being “immediately preceding” under a strict reading. The “unaccompanied by any corresponding presequence” limits the claim to designs that do not encode a signal peptide/presequence that corresponds to the native form. What do dependent claims 2–16 add? Claims 2–16 narrow claim 1 to specific mature interferon amino-acid sequences identified as SEQ ID NO:45–59, each with the condition that: the N-terminal amino acid is cysteine. This turns claim 1’s broad “mature leukocyte interferon (165–166 aa)” into a closed set of specific mature sequences. What do claims 17–22 cover beyond the DNA? Claims 17–19 are manufacturing process claims: culturing a bacterium transformed with a replicable bacterial expression vehicle containing a claimed DNA, where the vehicle expresses the mature interferon (165–166 aa; and for certain claims, using specific SEQ ID-linked DNA variants). Claims 20–22 are product-by-transformation / organism claims: a bacterium transformed with the claimed DNA, narrowed to E. coli and then E. coli K-12 strain 294 in claims 21–22. How strong is the patent estate for US 6,482,613 based on claim structure and likely claim scope? Where claim strength typically concentrates Strength generally concentrates in claim categories that are easier to show by documentation and sequence identity: DNA encoding claims (1–16): sequence-based; infringement can turn on whether the defendant’s construct encodes the specified mature interferon and includes an ATG immediately upstream of the N-terminal codon. Bacterial expression vehicle/process claims (17–22): enforceability is often tied to production records, plasmid maps, and sequence verification of expression constructs. Where enforceability is likely more contested Claim 1’s phrase “unaccompanied by any corresponding presequence or portion thereof” can generate interpretive disputes: What is the “corresponding presequence” for each mature leukocyte interferon variant? If a defendant uses a leaderless mature protein but includes translation-related elements (not a biologically “presequence”), the question is whether those elements are considered a “portion thereof” or merely upstream genetic context. Still, because the claim is written as a protein-length and “no presequence” requirement, the constraint is not open-ended. A defendant would usually mitigate risk by using different protein processing, different construct architecture, or different mature sequence identities. What patents (and claim components) in US 6,482,613 map to nucleic acid sequence and translation start design? Key claim construction hotspots “ATG immediately preceding the codon” This is a specific drafting choice that targets bacterial expression designs where translation initiates at an ATG right before the N-terminal amino acid codon. A design that inserts extra nucleotides between the ATG and the codon might aim to avoid “immediately preceding,” though practical bacterial translation typically depends on proximity. “mature human leukocyte interferon (165–166 amino acids)” This anchors the claim to a size range that reduces the universe of interferon variants. It also helps distinguish mature interferons that are longer or shorter (including engineered forms with extra residues). “unaccompanied by any corresponding presequence or portion thereof” This excludes constructs encoding signal peptides or prepro regions that are part of a native precursor architecture. It also creates an argument surface if a construct includes any processing-related region considered part of the “corresponding presequence.” Practical infringement proof points Gene/ORF sequencing to establish: the encoded polypeptide length (165–166), identity of the mature interferon sequence (SEQ ID NO mapping), and the presence and placement of ATG relative to the N-terminal codon. For process/organism claims: transformed host strain identity (for claims 21–22), expression plasmid sequence (for claims 17–19), and confirmation the host expresses the mature protein without presequence. Which mature leukocyte interferon sequences are locked into dependent claims (SEQ ID NO:45–59)? Dependent claims 2–16 define multiple mature interferon amino-acid sequences (SEQ ID NOs 45–59) and fix the N-terminal amino acid as cysteine. The legal consequence is that infringement of claims 2–16 depends on whether a defendant’s mature product matches one of those defined sequences. Claim coverage split: Claim 1: broader sequence coverage limited by mature interferon identity + 165–166 aa + ATG upstream + no presequence. Claims 2–16: narrower to specific enumerated sequences. Commercial implication: If a competitor uses a mature interferon sequence not matching those SEQ IDs (even if still “mature leukocyte interferon”), they may avoid dependent-claim infringement and potentially weaken whether claim 1 still reads, depending on whether the competitor product still satisfies the “mature human leukocyte interferon” definition and the 165–166 aa requirement. How do the bacterial production claims expand risk for generic or follow-on manufacturers? What claims 17–19 cover Claims 17–19 cover manufacturing by culturing transformed bacteria where the expression vehicle contains the claimed DNA. Two layers of risk: DNA-level risk: infringement is triggered by the DNA included in the vehicle. Process-level risk: the act of culturing the transformed bacterium to express the mature interferon can infringe. What claims 20–22 cover Organism claims create additional pathways for enforcement: If a manufacturer produces in-house using a transformed host, the host can fall within “a bacterium transformed with a DNA according to claims 1–16.” Claim 22 escalates specificity to E. coli K-12 strain 294. In litigation, organism claims often test whether the defendant’s product strain and construct match the transformation requirement. Strain identity can be a hard pin, but most commercial processes do not typically document “K-12 strain 294” specifically unless it is their exact maintained strain. When does US 6,482,613 lose exclusivity, and what are key U.S. timeline constraints? No timeline calculations can be produced from the claim text alone. A full exclusivity and expiration analysis requires at least the filing date, priority chain, and any PTA/TSA events. This information is not provided in the record supplied here. What would a Paragraph IV or biosimilar-type challenge look like for this patent? Small-molecule Paragraph IV context: likely not applicable directly US 6,482,613 is a nucleic acid and bacterial expression patent. If the commercial product is interferon expressed in bacteria, the legal structure differs from classic small-molecule generic Paragraph IV practice. Biologic/biosimilar analog: more likely If the product is an interferon biologic, the main legal challenge route in practice is tied to biosimilar pathway and patent listing mechanics rather than classic ANDA Paragraph IV. Still, the technical claim categories here focus on construct and expression method, which are more likely to show up as enforceability anchors in a biologic’s patent landscape. How does US 6,482,613 compare with competing interferon gene patents in typical claim strategies? Common competitor strategies to avoid these claims Different start architecture Use non-ATG initiation, engineered ribosome binding/start configurations, or alter upstream coding context such that no ATG is “immediately preceding” the N-terminal codon. Encode a different precursor design Include a processing sequence that is not “unaccompanied by any corresponding presequence,” or use a precursor with a different presequence identity and processing route, avoiding the “no corresponding presequence” limitation. Use different mature sequence identities Make mature interferon variants that do not match SEQ ID NO:45–59 and potentially don’t satisfy the claim-1 “mature human leukocyte interferon” identity constraint. Expression in non-bacterial systems If claims are tightly tied to “culturing a bacterium transformed with…” then production in yeast or mammalian systems can be a literal-claim avoidance pathway, depending on how the claim language is enforced and whether broader dependent claims exist outside 6,482,613. Where competitors may still be exposed Even with different host systems, claims 1–16 (DNA claims) can still be triggered if the accused entity uses the same DNA constructs anywhere in the chain, subject to jurisdictional proof. What is the Orange Book status of US 6,482,613? Orange Book status cannot be determined from the claim text provided. Orange Book listings require the associated NDA and the patent-to-product mapping, which is not supplied. Key litigation and settlement facts for US 6,482,613 No litigation docket, settlement terms, or enforcement events are provided in the record supplied here. A claims-and-patent landscape analysis without those facts cannot accurately state litigation impact. Key Takeaways US 6,482,613 is a sequence- and construct-focused patent targeting DNA encoding mature human leukocyte interferon (165–166 aa) that is not accompanied by a corresponding presequence, with a defining ATG immediately upstream of the N-terminal codon. Dependent claims 2–16 narrow protection to enumerated mature interferon sequences (SEQ ID NO:45–59) with N-terminal cysteine. Claims 17–22 extend the reach into bacterial expression: culturing transformed bacteria using a replicable expression vehicle containing the claimed DNA, plus organism claims including E. coli and E. coli K-12 strain 294. The claim scope suggests the highest infringement risk for competitors is use of the same mature sequence designs and the same translation start architecture in bacterial expression constructs. Expiration/exclusivity timing and Orange Book mapping cannot be determined from the supplied information. FAQs Does US 6,482,613 cover plasmids or only naked DNA sequences? What design changes can avoid literal infringement of the “ATG immediately preceding” requirement? If a manufacturer uses a different host (yeast or mammalian), are claims 17–19 still at risk? How do SEQ ID NO:45–59 dependencies affect product-by-product infringement for interferon variants? Can infringement be established without proof of actual expression if the DNA construct is used internally? References No cited sources are provided in the input, so no APA reference list can be generated. More… ↓ ⤷ Start Trial

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Llc	PEGINTRON	peginterferon alfa-2b	Injection	103949	January 19, 2001	6,482,613	2008-01-19
Merck Sharp & Dohme Llc	SYLATRON	peginterferon alfa-2b	For Injection	103949	March 29, 2011	6,482,613	2008-01-19
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Country	Patent Number	Estimated Expiration
Zimbabwe	14781	⤷ Start Trial
South Africa	814375	⤷ Start Trial
Yugoslavia	162281	⤷ Start Trial
Yugoslavia	47700	⤷ Start Trial
United States of America	6610830	⤷ Start Trial
U.S.S.R.	1414319	⤷ Start Trial
Slovenia	8111622	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration

Patent: 6,482,613

Summary for Patent: 6,482,613