Patent: 7,189,827

Summary for Patent: 7,189,827

Title:	Modified peptides as therapeutic agents
Abstract:	The present invention concerns fusion of Fc domains with biologically active peptides and a process for preparing pharmaceutical agents using biologically active peptides. In this invention, pharmacologically active compounds are prepared by a process comprising: a) selecting at least one peptide that modulates the activity of a protein of interest; and b) preparing a pharmacologic agent comprising an Fc domain covalently linked to at least one amino acid of the selected peptide. Linkage to the vehicle increases the half-life of the peptide, which otherwise would be quickly degraded in vivo. The preferred vehicle is an Fc domain. The peptide is preferably selected by phage display, E. coli display, ribosome display, RNA-peptide screening, or chemical-peptide screening.
Inventor(s):	Feige; Ulrich (Newbury Park, CA)
Assignee:	Amgen Inc. (Thousand Oaks, CA)
Application Number:	10/632,388
Patent Claims:	see list of patent claims

Comprehensive Analysis of United States Patent 7,189,827 (TPO-Mimetic Fc Fusions): Claim Scope, Likely Prior Art Anchors, and US Patent Landscape

US Patent 7,189,827 claims Fc-fused TPO-mimetic peptide multimers where at least one of the Fc-linked arms is present and neither fusion arm is a native protein. The claim set is built to cover (i) Fc domain fusion formats, (ii) a library of randomized TPO-mimetic peptide sequences, and (iii) specific Fc/peptide embodiments tied to SEQ ID NOs and peptide tables. The patent’s enforceable reach will hinge on how narrowly the “TPO-mimetic” definition and the peptide sequence randomness are construed, and whether an accused product can be designed around the specific SEQ ID–anchored embodiments while still practicing the broad structural formula.

Because the request is limited to the claims text provided and no bibliographic payload (publication number, assignee, prosecution history, specification details, or prosecution outcomes) is supplied, this analysis is confined to claim-structure interpretation and the legal “attack/defense” framework that can be applied to this claim language as written, without importing external facts.

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What exactly does US Patent 7,189,827 claim: Fc domain fused to randomized TPO-mimetic peptide multimers?

Core claim (Claim 1) is a composition-of-matter structural formula that covers an Fc domain (F¹) linked on one or both sides (X¹ and X²) to TPO-mimetic peptide sequences P¹..P⁴ via linkers (L¹..L⁴), where each X arm is constructed from 1 to 4 peptide/linker units in defined order. The claim also requires that the fusion arms are not native proteins and that at least one arm (a or b) is present.

Claim 1 breakdown (functional and structural hooks)

• Backbone: F¹ is an Fc domain.
• Arm architecture: X¹ and X² each follow one of:
  • -(L¹)ᶜ–P¹
  • -(L¹)ᶜ–P¹–(L²)ᵈ–P²
  • -(L¹)ᶜ–P¹–(L²)ᵈ–P²–(L³)ᵉ–P³
  • -(L¹)ᶜ–P¹–(L²)ᵈ–P²–(L³)ᵉ–P³–(L⁴)ᶠ–P⁴
• Randomized peptide definition: P¹..P⁴ are each “independently randomized TPO-mimetic peptide sequences.”
• Linkers: L¹..L⁴ are independently linkers.
• Arms on one or both sides: a and b are each 0 or 1, and at least one of a or b is 1.
• Non-native protein constraint: neither X¹ nor X² is a native protein.
• Peptide length: “peptide” refers to molecules 2 to 40 amino acids.
• Multimer coverage: explicitly includes “multimers thereof.”

Immediate claim-construction pressure points

1. “TPO-mimetic peptide sequences” as a functional claim limitation.
   Functional descriptors in composition-of-matter claims often drive validity disputes (enablement/indefiniteness) and infringement disputes (do products meet the functional criterion?).

2. “Randomized” sequences without a hard boundary.
   “Randomized” can be interpreted as a genus claim over a set of sequences defined by rules (e.g., positions subject to randomization) but it can also be argued as an attempt to claim outcomes without sufficiently defined variation.

3. Non-native protein restriction (“neither X¹ nor X² is a native protein”).
   This can become a design-around mechanism. If an accused construct is argued to be “native,” it would fall outside scope. Conversely, challengers can argue that “native protein” is unclear or that many recombinant constructs are still “not native proteins” as written.

4. Peptide length range (2 to 40 aa) breadth.
   A 39-aa window is large. It can capture substantial sequence diversity for “randomized” peptides, increasing coverage but also increasing vulnerability to enablement challenges if the specification does not supply adequate working examples across the range.

5. Multimers.
   “Multimers thereof” introduces oligomeric products into scope, which matters for Fc fusions that can form dimers/aggregates. Infringement may depend on whether the marketed species is within the claimed multimer definition.

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How broad are the dependent claims: do they create narrow “design-in” embodiments or add more variables?

Claims 2–4: symmetry variants and truncations

• Claim 2: X¹–F¹ or F¹–X² (single-arm fusions).
  This is narrower than Claim 1’s “at least one arm,” but it isolates a specific arrangement: only one arm on either N- or C-facing side of the Fc.

• Claims 3–4: F¹-(L¹)ᶜ–P¹ and F¹-(L¹)ᶜ–P¹-(L²)ᵈ–P².
  These narrow to one or two peptide units per arm.

Practical implication: These claims create additional infringement hooks if the accused product uses only 1 or 2 peptide units. If a defendant’s construct uses 3 or 4 units, Claims 3–4 may not read but Claim 1 still could.

Claims 5–6: Fc subclass narrowing

• Claim 5: F¹ is an IgG Fc domain.
• Claim 6: F¹ is an IgG1 Fc domain.

Practical implication: IgG and especially IgG1-specific limitations can narrow the set of accused Fc formats. However, Claim 1 already says F¹ is an Fc domain, so these dependent claims can strengthen enforceability against IgG1-only products and provide fallback positions.

Claims 7–10: SEQ ID NO and Table 6 embodiments (anchor points)

• Claim 7: F¹ comprises sequence of SEQ ID NO: 2.
• Claim 8: P¹ is a TPO-mimetic peptide sequence selected from Table 6.
• Claim 9: F¹ comprises SEQ ID NO: 2 (again) with the Table 6 peptide selection in Claim 8.
• Claim 10: composition having a sequence selected from SEQ ID NOS: 6 and 12.

Practical implication: These dependent claims matter because they can be used to:

• establish a “core literal infringement” zone around specifically disclosed sequences, and
• survive invalidity attacks that target functional/randomized genus claims, if the specific SEQ ID embodiments remain valid.

In litigation, plaintiffs typically argue genus coverage (Claim 1) and then plead dependent claims as alternative theories.

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What is the likely “claim taxonomy” for infringement: does it look like a genus or a set of layered embodiments?

US 7,189,827 is structured as a layered claim set:

1. Genus structural formula (Claim 1): covers a broad family of Fc–TPO-mimetic peptide fusions with 1–4 peptide units per arm and one or two arms.
2. Format-specific subsets (Claims 2–4): single-arm and 1–2 peptide unit per arm constraints.
3. Fc subclass fallbacks (Claims 5–6): IgG and IgG1 restrictions.
4. Specific sequence fallbacks (Claims 7, 8, 9, 10): SEQ ID NO and Table 6 peptide selections.

This architecture is typical of patents intended to withstand partial invalidity: even if the broad functional genus is attacked, the specific anchored embodiments can remain enforceable.

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Where do legal vulnerabilities likely concentrate: indefiniteness, enablement, written description for “randomized TPO-mimetic peptide sequences”?

This patent’s risk profile, based solely on claim wording, clusters around three doctrinal pressure points.

1) Enablement and written description against a “randomized” functional genus

• The claim sweeps P¹..P⁴ across randomized TPO-mimetic sequences with length 2–40 aa.
• The enforceability of such a genus typically depends on whether the specification teaches how to make and identify sequences that are TPO-mimetic across the breadth claimed.

If the specification provides only limited exemplars or a narrow mapping between “randomized” and “TPO-mimetic activity,” challengers can argue the patentee is claiming beyond what the disclosure supports.

2) Indefiniteness risk for functional scope (“TPO-mimetic” and “neither X¹ nor X² is a native protein”)

• “TPO-mimetic” is functional. Without an explicit assay threshold in the claim language, disputes can arise over what constitutes “TPO-mimetic.”
• “Native protein” can be contentious if an accused construct’s origin and sequence identity are debated. The claim uses “neither X¹ nor X² is a native protein,” which invites fights over characterization.

3) Claim breadth vs. structural definiteness

Even though the architecture is structural, the functional designation for P¹..P⁴ expands the effective claim scope. Defendants may attempt to recast the claimed subject matter as an attempt to claim activity rather than structure.

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How strong is the claim estate for licensing and litigation: what would an infringement analysis focus on?

Infringement elements to map to an accused product

1. Fc domain type
   Determine if the accused construct’s F¹ is an Fc domain. If yes, check whether it is IgG or IgG1.

2. Arm architecture
   Identify whether X¹ and/or X² exist and whether each arm is built as a sequence of linker-peptide units in the permissible counts (1–4) and order in the claim.

3. Peptide “randomized TPO-mimetic” correspondence
   Compare P¹..P⁴ definitions and the peptide length range (2–40 aa). Map each peptide subunit to the claim’s peptide concept (length and sequence rules).

4. Functional characterization of “TPO-mimetic”
   Litigation would likely center on assays or binding/functional potency data demonstrating whether the peptide portion is TPO-mimetic.

5. Non-native protein constraint
   Determine whether X¹ and X² are “native proteins.” This is likely a low-margin dispute unless an accused construct uses sequence identity to a naturally occurring protein fragment.

6. Multimer status
   If the accused product is oligomeric, evaluate whether it qualifies as a “multimer” within claim meaning. If only monomer is marketed, defendants argue out-of-scope.

Best plaintiff position

A plaintiff’s strongest path is likely through dependent claims tied to specific sequences (SEQ ID NO: 2; Table 6 peptides; SEQ ID NOS: 6 and 12). Those create literal infringement anchors even if functional/genus claims face broader scrutiny.

Best defendant position

A defendant likely seeks to:

• use different Fc subclasses or engineered Fc variants, and/or
• use peptide sequences outside the Table 6 selections and avoid the SEQ ID–anchored sequences, and/or
• dispute that their peptides meet “TPO-mimetic” as claimed.

Because Claim 1 remains broad, design-around must address the claim’s overall structure and functional definition, not just one dependent embodiment.

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What design-arounds are suggested by the claim language itself?

1) Change peptide count per arm

If an accused construct uses more than four peptide units, it may fall outside Claim 1’s defined X¹/X² architectures. If it uses fewer (zero on one side), Claim 2 covers one-arm configurations; but Claim 1 already requires at least one arm.

2) Avoid “randomized TPO-mimetic peptide sequences” definition

If the accused peptide is not within the patent’s definition of “randomized TPO-mimetic,” the functional limitation is where scope can break. Practically, this becomes an evidentiary battle.

3) Use Fc domains that do not match the dependent IgG1/SEQ ID constraints

If a product uses an Fc domain that is not IgG1 or lacks SEQ ID NO: 2 sequence, it may avoid Claims 5–7. However, Claim 1 still covers any Fc domain unless other constraints narrow it.

4) Use constructs where X¹ or X² arguably equals a “native protein”

This is conceptually a carve-out, but it is likely hard to execute for Fc-peptide fusions because X¹/X² are explicitly “not native proteins” in the claim. Still, if any accused component matches a naturally occurring protein sequence fragment, the argument could be tested.

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What does the US patent landscape likely look like around this patent type (Fc-TPO mimetic fusion)?

The request asks for a “comprehensive and critical analysis” of the “claims and the patent landscape” for this specific US patent number, but only the claim text is provided. Without the publication data, assignee, priority, or specification details, an external landscape mapping (continuations, related families, opposition/court records, Orange Book listings, competitors) cannot be produced accurately within the constraint that the response must be complete.

Accordingly, the landscape section below is limited to claim-typology landscape: the kinds of patents that typically surround this claim format and how they affect freedom-to-operate and litigation risk.

Adjacent patent families commonly implicated by this claim type

1. TPO-mimetic peptide sequence libraries
   Independent patents cover specific TPO-mimetic peptides, variants, and peptide randomization rules.

2. Fc fusion scaffolds and Fc engineering
   Separate patents may cover IgG Fc sequences, Fc glycoengineering, dimerization/hinge formats, and linker designs.

3. Linker technologies
   Linker patents cover stability, protease resistance, cleavage sites, and polymeric or peptide linkers.

4. Multimerization and assembly methods
   If “multimers” is central, manufacturing/aggregation control patents can shape how literal infringement is argued for different species (monomer vs dimer vs higher-order).

How that translates into litigation strategy

• If US 7,189,827’s genus is attacked, the plaintiff typically relies on the SEQ ID/Table 6 dependent claims.
• Defendants typically counter with either:
  • prior-art peptide sequence patents that anticipate the “randomized TPO-mimetic” scope, or
  • prior-art Fc fusion patents that render the combination obvious, while still challenging the functional limitation.

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Timeline and exclusivity questions: what do claims like these imply about enforceability windows?

Without filing dates, priority dates, or term adjustments, a precise “when does it lose exclusivity” answer cannot be generated. But structurally, the claim set implies a long-lived enforcement objective: layering genus + anchored SEQ ID embodiments to preserve value over time as competitors iterate peptide variants.

In practice, the “window” analysis in this patent class usually turns on:

• patent term (filed-to-issue-to-expiry mechanics),
• any patent term adjustment, and
• whether the patent is asserted against a product with the same Fc-peptide sequence architecture.

Because those inputs are not provided, no dates are stated.

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Key Takeaways

• Claim 1 is a broad Fc–TPO-mimetic peptide fusion genus: Fc domain (F¹) with one or two arms (X¹/X²), each arm defined as 1–4 linker–peptide units, with each peptide being a “randomized TPO-mimetic” sequence of 2–40 aa.
• Claims 2–4 carve out common formats: single-arm fusions and shorter peptide unit counts (1–2).
• Claims 5–7 and 8–10 add enforceability anchors using IgG1/SEQ ID NO: 2 and Table 6 peptide selections plus specific SEQ ID NO embodiments.
• The main infringement and validity battlegrounds are functional: whether the accused peptides meet “TPO-mimetic” and whether the “randomized” genus is supported and sufficiently definite.
• Design-arounds must address more than one parameter: Fc type, peptide unit architecture, peptide sequence space, and functional “TPO-mimetic” character.

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FAQs

1) How would a court map “multimers thereof” to an accused Fc fusion product?
By assessing whether the marketed/accused species forms the claimed multimeric state and whether that state is encompassed by the patent’s claim meaning.

2) What is the highest-risk claim limitation for “randomized TPO-mimetic peptide sequences”?
The functional scope attached to randomized peptide sequences, which can raise enablement, written description, and indefiniteness issues.

3) Can a defendant avoid the patent by changing only the linker (L¹–L⁴)?
If the linker still fits the claim’s “linker” construct used in the defined architecture, simply changing linker identity may not be sufficient. The infringement map must address whether the overall formula elements still read on the accused construct.

4) Do the SEQ ID NO-dependent claims create a narrower “literal infringement” pathway?
Yes. Claims tied to specific Fc (SEQ ID NO: 2) and specific peptide selections (Table 6; SEQ ID NOS: 6 and 12) provide sequence-specific anchors that can be easier to prove than genus coverage.

5) If a competitor uses a different Fc subclass, what claims remain available to a patentee?
Claim 1 still covers “an Fc domain” broadly, while Claims 5–7 limit to IgG and particularly IgG1 or the specific SEQ ID NO: 2 Fc sequence. The remaining infringement theory typically shifts to Claim 1 unless the Fc element is designed to fall outside the Fc domain definition.

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References

No sources were cited because the prompt provided only the claim text and did not include bibliographic or prosecution/legal records for US Patent 7,189,827.

Details for Patent 7,189,827

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen Inc.	NPLATE	romiplostim	For Injection	125268	August 22, 2008		2023-07-31
Amgen Inc.	NPLATE	romiplostim	For Injection	125268	July 22, 2019		2023-07-31

International Patent Family for US Patent 7,189,827

Country	Patent Number	Estimated Expiration
South Africa	200102753
Yugoslavia	25901
World Intellectual Property Organization (WIPO)	0024782
World Intellectual Property Organization (WIPO)	0183525
United States of America	2004044188
United States of America	2004053845
United States of America	2004057953