United States Patent 12,599,606 (US 12,599,606): Scope and US Patent Landscape for Lazertinib Plus EGFR/c-Met Bispecific Antibody in Advanced/Metastatic EGFR Exon 19 Del/Exon 21 L858R NSCLC
US 12,599,606 claims a combination regimen in advanced or metastatic NSCLC harboring EGFR Exon 19 deletions or EGFR exon 21 L858R, using once-daily lazertinib (with defined dose bands including 80 mg, 160 mg, 240 mg) together with an isolated bispecific anti-EGFR/c-Met antibody defined by specific CDR sequences and structural/glycosylation attributes. The claim set is anchored to (1) an EGFR mutation-defined NSCLC patient group, (2) a dosing schedule and dose range for lazertinib, and (3) a structurally specific IgG1 bispecific antibody, with additional narrowing to brain metastasis and particular antibody structural variants (IgG1 isotype, defined VH/VL and HC/LC sequences, biantennary glycofucose range, and lazertinib mesylate hydrate).
What is the claim scope of US Patent 12,599,606 for lazertinib plus an EGFR/c-Met bispecific antibody?
Featured snippet answer: The patent claims a method of treating advanced or metastatic EGFR exon 19 deletion or exon 21 L858R NSCLC by administering once-daily lazertinib (about 20 mg to about 320 mg, with explicit sub-ranges and single-dose values) together with a structurally defined isolated EGFR/c-Met bispecific antibody. Dependent claims narrow to brain metastasis and to specific antibody sequence/CDR sets, IgG1 isotype, defined HC/LC sequences, and biantennary glycan fucose content (about 1% to about 15%). A dependent claim also specifies lazertinib mesylate hydrate.
Core independent claim 1: what is actually required to infringe
Claim 1 requires all of the following elements:
-
Disease and population limitation
- “cancer is advanced or metastatic non-small cell lung cancer (NSCLC)”
- with EGFR Exon 19 deletions or EGFR exon 21 L858R substitution mutations
-
Drug 1 (small-molecule): lazertinib
- administered once daily
- in an amount about 20 mg to about 320 mg once daily
- and lazertinib may be provided as:
- a solvate, hydrate, tautomer, or
- a pharmaceutically acceptable salt
-
Drug 2 (biologic): isolated EGFR/c-Met bispecific antibody
- administered in a “therapeutically effective amount”
- is an isolated bispecific anti-EGFR/c-Met antibody
- no further functional limitation appears in claim 1 beyond being an EGFR/c-Met bispecific and being isolated.
Practical scope implication: Claim 1 is broad as to the antibody’s general nature (bispecific anti-EGFR/c-Met, isolated) but becomes highly specific in dependent claims 7–11 and 12 (and likely in the specification via sequence definitions tied to the SEQ ID numbers).
Dependent claims: what narrows the method
- Claim 2 (narrow clinical subset): Claim 1 where the subject exhibits brain metastasis.
- Claims 3–6 (dose embodiments):
- Claim 3: lazertinib 80–240 mg once daily
- Claim 4: lazertinib 240 mg once daily
- Claim 5: lazertinib 160 mg once daily
- Claim 6: lazertinib 80 mg once daily
- Claims 7–10 (antibody sequence/CDR and variable region identity):
- Claim 7 defines explicit CDRs for:
- EGFR-binding domain: HCDR1–3 (SEQ ID 1–3) and LCDR1–3 (SEQ ID 4–6)
- c-Met-binding domain: HCDR1–3 (SEQ ID 7–9) and LCDR1–3 (SEQ ID 10–12)
- Claim 8 maps those into VH/VL pairs:
- EGFR-binding: VH (SEQ ID 13) and VL (SEQ ID 14)
- c-Met-binding: VH (SEQ ID 15) and VL (SEQ ID 16)
- Claim 9 requires an IgG1 isotype.
- Claim 10 defines explicit HC1/LC1/HC2/LC2 sequences (SEQ ID 17–20).
- Claim 11 (glyco-attribute): biantennary glycan structure with fucose content 1% to 15%.
- Claim 12 (salt/hydrate embodiment): lazertinib is lazertinib mesylate hydrate.
Practical scope implication: Even if a competitor uses a different EGFR/c-Met bispecific with different CDRs, infringement would typically depend on whether the dependent-claim restrictions are met. If the competitor’s antibody does not match the SEQ ID-defined CDR/VH/VL/HC/LC patterns and the fucose range, claim 1 still requires only “isolated bispecific anti-EGFR/c-Met antibody,” but claim coverage strength usually hinges on how dependent claims are used in claim construction and enforcement strategy. Without the full specification and prosecution history, enforcement strategy cannot be mapped precisely, but the text shows a clear attempt to claim both generic bispecific combination treatment (claim 1) and specific antibody implementations (claims 7–11).
What the SEQ ID limitations mean for design-around
The strongest design barrier is the antibody sequence and glyco-structure:
- CDR identity constraints (claim 7): Any altered CDR set likely avoids literal infringement of dependent claims 7 (and typically also 8, 9, 10 where tied).
- VH/VL pairing (claim 8) and HC/LC mapping (claim 10): Using different variable region sequences or different chain pairing can avoid literal satisfaction.
- IgG1 isotype (claim 9): A non-IgG1 isotype may avoid claim 9.
- Fucose range (claim 11): If the therapeutic antibody’s glycosylation profile produces fucose outside 1%–15%, claim 11 is avoided. This is a manufacturing-and-analytics risk area, because glyco distribution can vary by cell line/process.
How broad are the lazertinib dose claims in US 12,599,606?
Featured snippet answer: The patent claims once-daily lazertinib dosing across about 20–320 mg/day, with explicit dependent embodiments at 80, 160, and 240 mg/day, and a broader band of 80–240 mg/day.
Dose matrix (as claimed)
| Claim |
Lazertinib administration |
Numeric scope (once daily) |
| 1 |
Once-daily lazertinib (solvate/hydrate/salt permitted) |
about 20 mg to about 320 mg |
| 3 |
Dependent dose band |
about 80 mg to about 240 mg |
| 4 |
Specific daily dose |
about 240 mg |
| 5 |
Specific daily dose |
about 160 mg |
| 6 |
Specific daily dose |
about 80 mg |
| 12 |
Form identity |
lazertinib mesylate hydrate (still within claim 1 dose limits as written) |
What “about” does for enforcement
“About” injects tolerance. Courts often treat “about” as a flexible range rather than a hard breakpoint, but the exact tolerated deviation depends on intrinsic evidence (specification, examples, and possibly prosecution). The independent claim’s numeric range is already wide, so a competitor operating at clinically customary doses within or near this band is at higher risk.
What patents protect the EGFR Exon 19/21 mutation NSCLC combination space with lazertinib?
Featured snippet answer: US 12,599,606 is a combination-method patent that targets lazertinib plus an EGFR/c-Met bispecific antibody in mutation-defined advanced/metastatic NSCLC. In practice, the broader IP landscape for “lazertinib + targeted antibodies/bi-specifics” is typically populated by three buckets: (1) lazertinib composition/solvate/salt and use patents, (2) antibody-specific patents (CDR sequences, bispecific formats, glyco-attributes, chain pairing), and (3) combination method patents tying the two for defined mutation subsets.
US 12,599,606’s role in that landscape: it is a method-of-use combination anchored to EGFR mutation stratification and specific antibody sequence embodiments.
Where other patents usually sit relative to this claim
- Lazertinib base patents: commonly cover the small molecule structure, polymorphs, solvates/hydrates (e.g., mesylate hydrate), and sometimes dosing regimens.
- Antibody patents: commonly cover the bispecific construct, CDR definitions, VH/VL pairing, IgG isotype, and engineering details (including glycosylation/fucose profile).
- Combination patents: tie the pair to patient selection (EGFR exon 19 del / exon 21 L858R) and clinical setting (advanced/metastatic NSCLC), sometimes including CNS/brain metastasis subsets.
What formulations and delivery forms are explicitly protected by US 12,599,606?
Featured snippet answer: The only explicit formulation embodiment is lazertinib mesylate hydrate (claim 12). The antibody is a structurally defined IgG1 bispecific with a specific glyco fucose range (claim 11).
Explicit formulation/attribute claims
- Lazertinib form (claim 12): lazertinib mesylate hydrate
- Antibody glyco-attribute (claim 11): biantennary glycan with fucose content 1%–15%
- Antibody format (claims 7–10):
- defined CDR sequences and variable region sequences
- IgG1 isotype
- defined heavy/light chain sequence assignments
Implication for regulatory and manufacturing changes
If an antibody is produced with different glycosylation affecting fucose distribution, claim 11 may be avoided. But if the antibody still matches CDR/VH/VL/HC/LC identity and is used in the same mutation-defined NSCLC treatment setting, claim 1 exposure remains.
When does US 12,599,606 expire, and what exclusivity windows matter for launch timing?
Featured snippet answer: Expiration timing is not determinable from the claim text alone. US 12,599,606’s issue/publication date, earliest priority date, and any PTA adjustments govern expiration. Without the bibliographic data, launch-risk windows cannot be stated accurately.
How strong is the patent estate for US 12,599,606 based on claim structure?
Featured snippet answer: Strength is high on the antibody-identifying dependent claims (CDR/VH/VL/HC/LC plus glyco fucose range) and moderate-to-high on clinical regimen scope due to mutation-defined NSCLC plus explicit lazertinib dose bands. The principal vulnerability is that claim 1’s antibody definition is broad at the generic level (“isolated bispecific anti-EGFR/c-Met antibody”), so enforcement depends on whether an accused product’s antibody matches the dependent-claim structural features and how claim 1 is construed against that match.
Claim coverage mechanics (what matters in litigation)
- Literal infringement leverage:
- High for antibody designs that recreate the SEQ ID-defined regions and glyco fucose content.
- Lower if the accused antibody changes CDRs/chain pairing/isotype/glyco distribution and thus only potentially maps to claim 1’s generic bispecific label.
- Claim interpretation leverage:
- SEQ ID definitions in dependent claims typically become central to construing the “bispecific antibody” scope in relation to the specification’s enablement and description.
What generic entry risks exist for combinations involving lazertinib and EGFR/c-Met bispecifics?
Featured snippet answer: “Generic” entry risks for the small-molecule component (lazertinib) are separate from biologic/bi-specific antibody substitution risks. A competitor may be able to use a non-literal alternative antibody while still using lazertinib if the antibody changes avoid the dependent-claim identity elements. Conversely, if the antibody is essentially within the claimed sequence space, combination method claims constrain design-around more directly.
Risk patterns
- Small-molecule pathway substitutes (lazertinib)
- If lazertinib itself is not protected by separate composition/use patents expiring later than the combination method, the small-molecule may be easier to swap.
- Biologic substitution (bispecific antibody)
- If the antibody’s CDRs and Fc/glyco attributes are constrained by multiple patents, substitution becomes the key barrier.
What patent litigation effects or Paragraph IV challenges could involve US 12,599,606?
Featured snippet answer: Litigation and Paragraph IV activity require docket and filing data that cannot be derived from the claim text. Claim language indicates it is a method-of-treatment combination patent; such patents are often asserted in alignment with biosimilar or generic launch attempts when the accused regimen mirrors the claimed mutation-defined treatment and dose schedule.
What is the Orange Book status of the lazertinib product implicated by US 12,599,606?
Featured snippet answer: Orange Book status depends on the specific NDA/BLA listed reference product, the listed drug name, and patent/extension listings (including method-of-use patents tied to that product). That cannot be determined from claim text alone.
Commercial impact: how does this claim likely map to real-world dosing and patient stratification?
Featured snippet answer: The regimen is aligned to an EGFR mutation-enriched NSCLC subgroup (Exon 19 deletion or L858R) and uses a once-daily lazertinib dose range with explicit daily dose embodiments (80/160/240 mg). If the combination is used in patients with brain metastasis, claim 2 adds a further enforceable narrowing element.
Patient and dosing constraints that drive payer/clinical protocol exposure
- Patient selection constraint: EGFR genotype positive, advanced/metastatic.
- Dose schedule constraint: once-daily.
- Dose magnitude constraint: about 20–320 mg/day and explicit 80/160/240 mg embodiments.
Key takeaways
- Claim 1 is the anchor: it combines lazertinib once daily (about 20–320 mg) with an isolated EGFR/c-Met bispecific antibody for advanced/metastatic EGFR exon 19 del or exon 21 L858R NSCLC.
- Dependent claims are the strongest structural hooks for enforcement: specific EGFR/c-Met bispecific antibody CDRs (SEQ ID sets), VH/VL assignments, HC/LC assignments, IgG1 isotype, and fucose content of a biantennary glycan range (1%–15%).
- Design-around is most feasible via antibody engineering that avoids the SEQ ID-defined CDR/VH/VL/HC/LC mappings and/or changes glyco fucose distribution and/or Fc/isotype.
- Lazertinib dose changes alone may not avoid exposure because claim 1 already spans a wide daily dose range and includes common explicit dose points as dependent embodiments.
- Expiration, Orange Book listings, and litigation outcomes cannot be stated from the claim text. Those require bibliographic and docket data.
FAQs
1) Does US 12,599,606 require the bispecific antibody to match the SEQ ID CDRs in claim 1?
Claim 1 requires an “isolated bispecific anti-EGFR/c-Met antibody” but the specific SEQ ID CDR/VH/VL/HC/LC definitions appear in dependent claims (not claim 1’s text). In infringement analysis, dependent-claim limitations are key where asserted through the doctrine of claim differentiation or where the accused antibody is matched to the dependent definitions.
2) If a competitor uses lazertinib at 60 mg once daily, is it outside the patent?
Claim 1 covers about 20 mg to about 320 mg once daily. A 60 mg once-daily dose would typically fall within that band as written.
3) How can an accused party reduce risk under claim 11’s glycofucose limitation?
By changing the antibody manufacturing process or cell line such that biantennary glycan fucose content is outside about 1% to about 15%, while still maintaining functional bispecific activity. This is a quality-by-design and analytics control issue.
4) Does claim 2 add a distinct infringement scenario for brain metastases?
Yes. Claim 2 narrows claim 1 to subjects exhibiting brain metastasis, creating an additional layer of limitation for that subgroup.
5) What is the most likely design-around entry point for a different EGFR/c-Met bispecific?
Avoiding the specific CDR/VH/VL and chain sequence identities (claims 7–10) and potentially altering isotype (claim 9) and glyco-fucose profile (claim 11), while also targeting patient population and regimen elements to the extent permitted by the remaining claim scope.
References (APA)
- US Patent 12,599,606. Method for treating cancer in a human subject. Claims as provided in prompt.
