Patent: 10,202,419

Summary for Patent: 10,202,419

Title:	Connective tissue stimulating peptides
Abstract:	Novel peptides are described which comprise an amino acid motif selected from the group consisting of \"PG\", \"GP\", \"PI\" and \"IG\" and having up to 10 amino acids upstream and/or downstream of the amino acid motif, wherein \"P\" in the motif is proline or hydroxyproline and the peptide stimulates the development, maintenance and repair of bone, cartilage and associated connective tissue. The invention further relates to pharmaceutical compositions of these peptides, as well as therapeutic and prophylactic uses of such peptides.
Inventor(s):	Sindrey; Dennis R. (Oakville, CA), Pugh; Sydney M. (Glenburnie, CA), Smith; Timothy J. N. (Kingston, CA)
Assignee:	Octane Orthobiologics Inc. (CA)
Application Number:	14/854,238
Patent Claims:	see list of patent claims

US Patent 10,202,419 Claims and U.S. Patent Landscape Analysis: Bone/Cartilage Peptide Motif Therapy, Controlled Release, and Calcium-Binding Chimeras

US Patent 10,202,419 is a U.S. method patent directed to administering short peptides containing proline/hydroxyproline-rich motifs (core motifs: GPI, PGP, LPG, GLP, PIG, IGP with limited flanking residues) for bone, cartilage, and associated connective tissue stimulation. The claim set expands beyond the motif to cover: (i) sequence variants, (ii) controlled sustained release via pharmaceutically acceptable carriers and biomaterial compounds, (iii) implant or coating-based local delivery, (iv) chimeric constructs with calcium-binding phosphoserine-rich sequences from extracellular matrix proteins, and (v) broad pharmacodynamic readouts and combinations with other osteogenic agents in the therapeutic regimen.

The patent’s defensibility in litigation turns on how narrowly the claims are construed around (a) the motif definition and proline/hydroxyproline placement and (b) the sufficiency of peptide identity standards for infringement when defendants use variant sequences, different flanking architectures, alternative sustained-release mechanisms, or non-phosphoserine calcium-binding approaches.

---

What is US Patent 10,202,419 protecting in the U.S.?

Core protection: Methods of stimulating development, maintenance, and repair of bone/cartilage/associated connective tissue by delivering a therapeutically effective peptide that includes a specified peptide motif (GPI, PGP, LPG, GLP, PIG, IGP) with up to 10 amino acids upstream and/or downstream of that motif, where P is proline or hydroxyproline, administered in an effective amount for an effective time.

Claim scope is method-of-use with composition mechanics embedded: Though framed as “method,” the claims capture delivery formats that look like combination-product architectures:

• Direct delivery of the motif-containing peptide (claim 1)
• Binding to a carrier and controlled/sustained release for >24 hours and specific time bands (claims 5–8)
• Local delivery via implant or coatings (claims 25–27)
• Systemic delivery enumerated by route (claim 24)
• Chimeric peptides with calcium-binding sequences (claims 17–19)
• Optional assessment endpoints (claim 20; 37)

Practical claim anatomy (how infringement gets made or broken)

(1) Motif + P/proline logic

• The motif is limited to: GPI, PGP, LPG, GLP, PIG, IGP
• The motif allows up to 10 residues on either side. This breadth is favorable to patentees against “short flanking” design-arounds, but it also raises construction issues: defendants can attempt to avoid motif inclusion altogether, or alter proline/hydroxyproline composition in the motif positions.

(2) Effective time and sustained-release limitations

• Claims 5–8 introduce a distinct protected delivery configuration: releasing the peptide in a controlled and sustained manner such that delivery is maintained for >24 hours, with dependent claims specifying time windows (≥48 hours, ≥1 week, ≥3 weeks, ≥6 weeks, ≥9 weeks, ≥12 weeks).
• If a defendant’s product is rapid-release or degrades quickly, these dependent claims become vulnerable.

(3) Carrier/biomaterial binding and implant architecture

• Carriers include a “pharmaceutically acceptable carrier” (claim 6) and a “biomaterial compound” (claims 10–11).
• Local delivery includes implants, coatings, and matrices (claims 25–27).
• Broad language (“biocompatible and/or biodegradable polymer,” claim 28) supports a wide range of sustained-release formats.

(4) Chimeric peptide calcium-binding sequences

• Claims 17–19 add a second axis: peptides linked to a chimeric peptide with a calcium binding sequence derived from specified proteins.
• The binding sequences are specified as phosphorylated serine-rich motifs (S* denotes phosphorylated serine) with multiple explicit sequence options (SEQ ID NOs 35–44).
• Defendants can attempt to swap the calcium-binding domain to a non-phosphoserine motif or to sequences not captured by the listed SEQ IDs.

---

Which exact peptide sequences are listed, and how much latitude do the claims leave?

The dependent claims enumerate multiple peptide sequences built from the motif elements and proline/hydroxyproline substitutions.

Enumerated “selected from” peptide sets (claims 4 and 29 and 38)

Claim 4 / 29 / 38 list the following peptides and mixtures:

• NGLPGPIGP* (SEQ ID NO.1)
• NGLPGPIG (SEQ ID NO.2)
• NGLP*GPIG (SEQ ID NO.3)
• NGLP*GPIGP* (SEQ ID NO.4)
• NGLPGP (SEQ ID NO.5)
• LPGP (SEQ ID NO.6)
• PGPIG (SEQ ID NO.7)
• NGLPGPIGP* (SEQ ID NO.8) (note: duplicated motif family member; wording aligns with NGLP + GPIG + P*)
• PGPIGP (SEQ ID NO.9)
• PGPIGPPGPR (SEQ ID NO.10)
• GPIG (SEQ ID NO.11)
• PGPIGPPGPRGRTGDA (SEQ ID NO.12)
• GPRGRTGDA (SEQ ID NO.13)
• PGPIGPP (SEQ ID NO.14)
• PGPIGP* (SEQ ID NO.15)
• PGPI (SEQ ID NO.16)
• GLPGPIG (SEQ ID NO.17)
• GPIGP* (SEQ ID NO.18)
• GPIGP (SEQ ID NO.19)
• PIGP (SEQ ID NO.20)

Claim construction implication: even with a broad “motif with up to 10 flanks” definition, the patent also hard-bakes many specific sequences into dependent coverage, reducing the ability to argue that only a narrow set is intended.

Specific “sequence has” dependents (claims 39–44)

• Claim 39: peptide is NGLPGPIGP* (SEQ ID NO.1)
• Claim 41: peptide is PGPIG (SEQ ID NO.7)
• Claim 42: peptide is GPIG (SEQ ID NO.11)
• Claim 43: peptide is PGPIGP* (SEQ ID NO.15)
• Claim 44: peptide is PGPIGPPGPRGRTGDA (SEQ ID NO.12)
• Claim 40: peptide further comprises S*S*S*EE (SEQ ID NO.37)

Latitude retained for defendants: Even if a defendant avoids an enumerated dependent sequence, infringement of independent claim 1 can still occur if their peptide includes one of the motifs with P/hydroxyproline in motif positions and has ≤10 upstream/downstream residues.

---

How do the claims define “P” and how does that matter for design-around?

Claim 1: “wherein ‘P’ in said motif is proline or hydroxyproline.”

• This means hydroxyproline is explicitly within scope.
• Defendants can attempt to use isosteres (e.g., substituting with β-methylproline analogs) or shift motif composition such that proline/hydroxyproline is not present at required motif “P” positions.
• However, the motif itself is a fixed three-amino-acid pattern in several cases, which makes “small substitutions” high-risk if the motif identity is still maintained.

---

What formulation and delivery barriers are built into the patent claims?

The strongest “product architecture” coverage is in claims 5–11 and 25–28.

Controlled and sustained release via binding to carrier (claims 5–8)

• Controlled and sustained release is required, with delivery for >24 hours.
• Dependent time bands extend out to ≥12 weeks.

Infringement pressure point: If a defendant uses a sustained-release mechanism that is not “binding to a pharmaceutically acceptable carrier” (claim 6) or does not demonstrate the effective time threshold in claim 7/8, the dependent coverage can fall away. Independent claim 1 remains, but it becomes harder for patentees if the defendant can argue its delivery is not “therapeutically effective time” in the claimed sense.

Local delivery via implants/coatings/matrices (claims 25–27)

• “Local delivery comprises injection or use with an implant.”
• Delivery by coating the peptide or filling/dispersing within the matrix of an implant.
• Also covers combining with granular/powdered biomaterial.

Polymers (claim 28)

• “combining the peptide with a biocompatible and/or biodegradable polymer.” This language is broad enough to include common implant polymers and hydrogels if used to deliver the protected peptide locally/sustainedly.

---

What is the calcium-binding chimeric peptide scope, and where are the legal pinch points?

Claims 17–19 are structurally more specific than claims 5–8.

Chimeric constructs are tethered to explicit binding sequences

• Calcium binding sequences come from specified proteins:
  • osteopontin, dentine matrix phosphoprotein, phosvitin, phosphohoryn, beta-casein, stratherin, matrix gla protein, riboflavin binding protein, alpha S1 casein
• Binding sequences are explicitly listed by SEQ ID NO: 35–44.
• Binding sequences are phosphoserine-rich using S* for phosphorylated serine.

Infringement hinge

A defendant that uses:

• a different calcium-binding domain not captured by the listed sequence set, or
• a non-phosphoserine calcium-binding approach, may avoid these dependent claims even if it still uses the peptide motif.

But independent claim 1 still covers delivery of the motif peptide without requiring the chimeric calcium-binding domain.

---

How do the method outcome criteria expand the evidentiary record?

Claims 20 and 37 add “assessing stimulation” by listing endpoints:

• bone mineral density/content
• alkaline phosphatase
• osteoblast proliferation
• bone nodule formation and mineralization
• chondrocyte proliferation
• intracellular calcium channeling assay
• collagen and proteoglycan assays

These do not add new chemical limitations; they broaden acceptable evidence of stimulation. That matters for both infringement proof and for invalidity defenses based on alleged lack of enablement. The listed endpoints align with typical in vitro and in vivo osteogenic/chondrogenic assays.

---

What other therapeutic agents are implicated by the claim set?

Claim 22 adds a regimen-like component: it states compositions may further comprise an agent including a wide list, such as:

• calcium salts and bone-forming matrix components (calcium phosphate, calcium sulfate, calcium carbonate, fibrin)
• hyaluronic acid, proteoglycans
• hormones and analogs (calcitonin, estrogen, estradiol, parathyroid hormone)
• prostaglandin A1
• bisphosphonic acids, ipriflavones, sodium fluoride, vitamin K
• bone morphogenetic proteins, fibroblast growth factor, platelet-derived growth factor, TGF, IGF-1/2
• endothelin, epidermal growth factor, leukemia inhibitory factor, osteogenin

This expands potential combination-product scope for infringement arguments, including challenges based on whether a competitor’s label, protocol, or clinical protocol uses such agents in combination with the protected peptide.

---

What does the patent likely cover commercially (use-cases and product formats)?

Covered indications in claim logic

• “stimulating the development, maintenance and repair” of:
  • bone
  • cartilage
  • associated connective tissue

The claims do not name specific orthopedic conditions, but they map to typical therapeutic targets such as:

• cartilage repair
• osteogenic regeneration
• bone defects where local delivery is used (implants, coatings, matrices)

Product formats implied by claims

• peptide plus carrier (general)
• peptide bound to biomaterial compound
• local implant coatings or peptide-filled matrices
• controlled sustained release polymer systems
• systemic administration routes also enumerated

The commercial enforcement risk is highest where a competitor uses:

1. motif-containing peptide sequences (including hydroxyproline variants) and
2. local implant or sustained-release system with the required effective-time profile.

---

How strong is the patent estate for this specific motif-based concept?

The provided text contains only the claim set and not:

• the priority dates
• the patent’s full specification disclosure scope
• the family’s related continuations/divisionals
• prosecution history
• the Orange Book or FDA regulatory linkages
• litigation or reexamination records
• claim count, remaining enforceability, or terminal disclaimer structure

Under those constraints, the only defensibility analysis possible is claim-structure strength:

Claim-structure strength factors

• Motif definition plus proline/hydroxyproline inclusion creates a conceptual “center of gravity” that can capture many close variants.
• Explicit dependent lists of multiple peptide sequences reduce escape from enumerated motif families.
• Delivery architecture claims for controlled release and implant localization raise the difficulty of complete design-around when product form is similar.

Claim-structure vulnerability factors

• Because claims are method-based with “therapeutically effective time,” proof disputes can arise around the operational delivery profile.
• Dependent chimeric calcium-binding claim set is narrow via explicit SEQ ID lists. If a competitor changes the binding domain, dependent coverage may be avoidable.
• The broad “up to 10 residues upstream and/or downstream” language can be litigated, especially if the defendant’s sequence length or flanking arrangement is argued to fall outside a reasonable construction.

---

What generic or biosimilar-style “entry risk” exists for a peptide method patent?

This is not a small-molecule drug with an Orange Book generic pathway. The practical entry risk is:

• competitors using different peptide motifs and/or non-overlapping sequence designs
• competitors using alternative sustained-release delivery systems that avoid the specific dependent limitations
• competitors who can avoid the motif inclusion entirely

A “Paragraph IV” equivalent does not map cleanly to peptide biologics, but the business question is similar: how easily can design-arounds carve out the motif and delivery architecture without losing efficacy.

---

Timeline: when does exclusivity expire?

This analysis cannot compute exclusivity or enforceability windows without:

• the patent issue date and priority date(s)
• whether the patent is subject to PTA adjustments
• terminal disclaimer details
• maintenance fee status
• any overlapping FDA exclusivity tied to an approved product

No timeline is provided in the prompt, so no enforceability dates are produced.

---

Key Takeaways

• US 10,202,419 protects a motif-based peptide method for stimulating bone/cartilage/connective tissue, where motif residues are constrained to GPI, PGP, LPG, GLP, PIG, IGP and the motif’s “P” is proline or hydroxyproline.
• The claims extend protection to specific peptide sequences (multiple SEQ ID NO variants) and to delivery architecture including controlled sustained release for >24 hours up to multi-week windows and local implant-based delivery formats.
• The calcium-binding chimeric peptide coverage is more narrowly constrained by explicit phosphorylated serine sequence sets (SEQ ID NOs 35–44). A different calcium-binding domain is a likely design-around axis for dependent claims.
• Combination-agent language is broad (claim 22), increasing litigation leverage where competitors co-administer or co-formulate osteogenic agents with the protected peptide.
• Infringement leverage is strongest when a competitor uses (i) a protected motif peptide and (ii) a sustained-release carrier/implant approach matching the effective-time and local delivery claim limitations.

---

FAQs

1. Can a competitor avoid US 10,202,419 by changing only peptide flanking residues?
   Not if the protected motif remains intact and the peptide stays within the “up to 10 amino acids” upstream/downstream framework; flanking changes alone are risky.

2. What is the most meaningful design-around lever: peptide sequence or release profile?
   Sequence: removing or altering the protected motif and “P” requirement. Release profile: avoiding controlled/sustained delivery for the claimed effective-time bands can defeat the dependent delivery claims, though independent motif coverage may remain.

3. Does the chimeric calcium-binding domain have to be present for infringement?
   No for independent claim 1, which is motif-delivery-based. The chimeric domain matters for dependent claims 17–19.

4. Do the listed “assessment criteria” create additional patentable steps beyond delivery?
   They broaden what qualifies as assessing stimulation, supporting infringement proof and assay evidence, but they do not replace the core delivery limitations.

5. How can local implant delivery increase infringement exposure?
   The implant/coating/matrix claims (25–27) directly match common orthopedic delivery architectures, especially when coupled with sustained release and motif-bearing peptides.

---

References (APA)

1. United States Patent 10,202,419. (claims text provided in prompt).

Details for Patent 10,202,419

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	NATPARA	parathyroid hormone	For Injection	125511	23-Jan-15		2035-09-15
Csl Behring Lengnau Ag	AFSTYLA	antihemophilic factor (recombinant), single chain	For Injection	125591	25-May-16		2035-09-15
Csl Behring Lengnau Ag	AFSTYLA	antihemophilic factor (recombinant), single chain	For Injection	125591	31-Mar-17		2035-09-15

International Patent Family for US Patent 10,202,419

Country	Patent Number	Estimated Expiration
Australia	2003221582
Brazil	0309877
Canada	2489009