Details for Patent: 5,198,533

United States Patent 5,198,533: Scope, Claims, and U.S. Landscape

What does US Patent 5,198,533 claim?

US 5,198,533 is an invention focused on a tightly defined peptide structure and its pharmaceutically acceptable acid addition salts. The claim set provided is at least two independent claim levels (Claim 1 and Claim 2). Claim 1 establishes the full sequence skeleton and the permissible identity of each variable residue. Claim 2 narrows one variable position (R3) to a single allowed residue identity.

Claim 1 (full scope of the asserted peptide identity)

Claim 1 recites a peptide with the formula:

X–R1–R2–R3–Ser–Tyr–R6–Leu–Arg–Pro–R10–NH2

with specific residue definitions:

• X = acetyl
• R1 = D-Nal(2)
• R2 = D-Phe(4Cl)
• R3 = D-Trp or D-Pal(3)
• R6 = D-Cit or D-Hci
• R10 = D-Ala
• plus pharmaceutically acceptable acid addition salts of the peptide

This claim is sequence-deterministic at every position except two positions that are defined as two-option sets:

• R3 (two alternatives)
• R6 (two alternatives)

So the peptide family size inside Claim 1 is 2 × 2 = 4 distinct peptide embodiments, all sharing the same backbone and the same fixed residues elsewhere.

Claim 2 (narrowing within Claim 1)

Claim 2 states:

• The peptide of Claim 1 wherein R3 is D-Pal(3).

That removes the D-Trp alternative and reduces the set size by half.

Enumerated peptide embodiments within Claim 1

Based strictly on the variable residues in Claim 1:

Total embodiments in Claim 1: 4

1. Acetyl–D-Nal(2)–D-Phe(4Cl)–D-Trp–Ser–Tyr–D-Cit–Leu–Arg–Pro–D-Ala–NH2
2. Acetyl–D-Nal(2)–D-Phe(4Cl)–D-Trp–Ser–Tyr–D-Hci–Leu–Arg–Pro–D-Ala–NH2
3. Acetyl–D-Nal(2)–D-Phe(4Cl)–D-Pal(3)–Ser–Tyr–D-Cit–Leu–Arg–Pro–D-Ala–NH2
4. Acetyl–D-Nal(2)–D-Phe(4Cl)–D-Pal(3)–Ser–Tyr–D-Hci–Leu–Arg–Pro–D-Ala–NH2

Total embodiments in Claim 2: 2

• 3 and #4 above.

Salt coverage (scope extension without changing peptide identity)

Claim 1 also covers pharmaceutically acceptable acid addition salts of the peptide. That does not change the peptide sequence in claim construction; it expands coverage to salt forms.

Practically, this means competitors using the same exact peptide sequence and switching only the counterion to a typical pharmaceutically acceptable acid may still fall within literal salt coverage depending on how the salts are characterized in infringement analysis.

How broad is the patent’s peptide scope versus typical peptide patents?

This is a narrow, sequence-defined peptide claim, not a broad “method of treatment” or “class of analogs with a general pharmacophore.” The claim uses a fixed terminal amide (NH2 at the C-terminus) and fixed side-chain substitutions at multiple positions.

Key breadth metrics:

1. Fixed backbone length and positions: The claim fixes an 11-residue peptide segment after the N-terminal acetyl cap and defines each residue position by identity.
2. Only two variable positions:
   • R3 has two permitted identities (D-Trp or D-Pal(3))
   • R6 has two permitted identities (D-Cit or D-Hci)
3. Strict residue identity at the remaining positions:
   • N-terminus: acetyl
   • R1: D-Nal(2)
   • R2: D-Phe(4Cl)
   • central: Ser–Tyr fixed
   • later: Leu–Arg–Pro fixed
   • C-terminus: D-Ala fixed
4. Salt inclusion: expands to acceptable acid addition salts but does not expand beyond the sequence itself.

In litigation terms, this structure typically translates into high validity-to-infringement specificity: fewer products can fall within literal scope, but if a product matches the sequence and salt category, infringement risk rises sharply.

What does the claim structure imply for design-around?

Because the claim is defined by exact residue identity at each position, design-around options are constrained to changing at least one of the defined residues outside the allowed alternatives.

High-impact change points

To avoid literal infringement of Claim 1, a product must change at least one of the following elements:

• Any of the fixed residues (X, R1, R2, Ser, Tyr, Leu, Arg, Pro, R10), or
• the allowed set boundaries at variable positions:
  • Make R3 neither D-Trp nor D-Pal(3)
  • Make R6 neither D-Cit nor D-Hci

Low-impact changes likely do not avoid literal coverage

• Switching among the two allowed R3 residues still stays within Claim 1.
• Switching among the two allowed R6 residues still stays within Claim 1.
• Changing the salt counterion, if it remains a pharmaceutically acceptable acid addition salt, likely keeps the product within the salt aspect of Claim 1.

Claim 2-specific design-around

To avoid Claim 2 (while still possibly falling under Claim 1), changing R3 away from D-Pal(3) to D-Trp is enough to remove the specific Claim 2 limitation, but it would still be within Claim 1 if the rest matches.

What is the patent landscape in the U.S. for this kind of peptide claim?

A complete U.S. landscape requires docket-by-docket retrieval of the bibliographic family and citation network (related applications, continuations, and relevant opposing patents). This response is limited to the claim text you provided and therefore can only map the landscape logic, not enumerate the actual U.S. patents without risking incorrect attribution.

Still, the landscape can be structured as two competing realities common to sequence-defined opioid/peptide analog portfolios:

1. Same-sequence competitors (highest risk)

   • Products matching all fixed residues with one of the permitted R3/R6 options.
   • Any acid addition salt that is pharmaceutically acceptable.

2. Analog competitors (primary design-around zone)

   • Products that change one of the fixed positions or move R3/R6 outside the permitted set.
   • Often accompanied by distinct pharmacology claims and separate composition-method filings.

Landscape risk map (sequence match logic)

The infringement risk increases monotonically with sequence identity.

What are the claim elements likely to be litigated first?

Sequence-defined peptide claims focus infringement analysis on:

1. Residue identity at each position
   • R1, R2, Ser, Tyr, Leu, Arg, Pro, R10 are fixed and usually easily verified by peptide sequencing or compositional characterization.
2. Assignment of variable positions
   • R3 and R6 are the only switches allowed inside Claim 1.
3. Salt identity
   • “Pharmaceutically acceptable acid addition salt” can become fact-intensive if a competitor uses an uncommon salt form or argues non-acceptability.

Because Claim 2 is a subset, the main additional fact issue for Claim 2 is whether R3 is D-Pal(3).

How does Claim 1 interact with Claim 2?

Claim 2 is a classic dependent claim that narrows scope without altering the peptide backbone:

• If a peptide has R3 = D-Pal(3) and all other Claim 1 conditions are met, it potentially infringes both.
• If a peptide has R3 = D-Trp, it can infringe Claim 1 but not Claim 2.

This creates a practical two-tier risk model for competitors:

• Determine which R3 option is used.
• Then determine whether R6 is D-Cit or D-Hci.
• Then confirm the full identity of fixed positions and acetylation status.

Business implications for R&D and licensing

1) Screening strategy

If this patent sits in a portfolio you care about, the screening target is narrow:

• Exact peptide sequence identity with acetyl N-terminus.
• Correct stereochemistry (D-forms) for each defined residue.
• Correct substitution patterns:
  • D-Phe(4Cl)
  • D-Nal(2)
  • D-Pal(3) when used
• Correct selection between D-Cit and D-Hci at R6.
• Correct C-terminal residue: D-Ala with terminal amide (NH2).

2) Licensing leverage

Given the claim’s narrowness, licensing leverage generally comes from:

• whether a lead candidate matches one of the 4 Claim 1 embodiments, and
• whether salts are being commercialized in forms captured by “pharmaceutically acceptable acid addition salt.”

If a candidate matches one of the embeddings, the patent can be a direct barrier to entry absent a carve-out, design-around, or a non-infringing alternative sequence.

Key Takeaways

• US 5,198,533 Claim 1 covers a sequence-defined acetylated peptide with a fixed backbone and only two variable positions: R3 = D-Trp or D-Pal(3) and R6 = D-Cit or D-Hci, plus pharmaceutically acceptable acid addition salts.
• Claim 1 yields 4 peptide embodiments; Claim 2 reduces to 2 embodiments by limiting R3 to D-Pal(3).
• Design-around is primarily achieved by changing at least one fixed residue or moving R3/R6 outside the two allowed options; changing only the salt counterion may not avoid coverage.
• Infringement analysis will concentrate on residue identity and salt acceptability, with R3 (for Claim 2) and R3/R6 (for Claim 1) as the key discriminators.

FAQs

1) How many distinct peptide sequences are covered by Claim 1?
Four: 2 choices for R3 (D-Trp or D-Pal(3)) times 2 choices for R6 (D-Cit or D-Hci), with all other residues fixed.

2) Does Claim 1 cover salt forms?
Yes. It covers pharmaceutically acceptable acid addition salts of the peptide sequence.

3) What additional limitation does Claim 2 impose?
Claim 2 requires R3 = D-Pal(3), excluding R3 = D-Trp.

4) Is it enough to change only the salt counterion to avoid infringement?
Not necessarily. If the alternative counterion is still within “pharmaceutically acceptable acid addition salts,” the salt aspect remains within Claim 1.

5) Where is the easiest place to design around?
At the claim’s discriminating positions: change R3 to a residue other than D-Trp or D-Pal(3), or change R6 to a residue other than D-Cit or D-Hci, or alter any fixed residue such as R1, R2, Ser, Tyr, Leu, Arg, Pro, or R10.

References (APA)

[1] United States Patent 5,198,533. Claims 1-2 (peptide formula and variable residue definitions as provided).