Patent: 10,293,037

Summary for Patent: 10,293,037

Title:	DNA vaccine for use in pancreatic cancer patients
Abstract:	The present invention relates to an attenuated mutant strain of Salmonella comprising a recombinant DNA molecule encoding a VEGF receptor protein. In particular, the present invention relate to the use of said attenuated mutant strain of Salmonella in cancer immunotherapy.
Inventor(s):	Lubenau; Heinz (Neustadt an der Weinstrasse, DE)
Assignee:	VAXIMM AG (CH)
Application Number:	15/994,766
Patent Claims:	see list of patent claims

US Patent 10,293,037 landscape and claim-scope analysis for Ty21a DNA vaccine encoding human VEGFR-2 (SEQ ID NO 1) at ≤1×10^9 CFU

Executive summary. US Patent 10,293,037 is directed to a Salmonella typhi Ty21a-based DNA vaccine that delivers a human VEGFR-2 (SEQ ID NO 1) via a defined expression cassette (including a specified pVAX10.VR2-1 plasmid architecture) with a single-dose CFU ceiling (≤1×10^9 CFU), used as cancer immunotherapy and optionally combined with chemotherapy/radiotherapy, including gemcitabine schedules and oral administration. The practical IP risk is concentrated in (i) the VEGFR-2 (SEQ ID NO 1) payload, (ii) the Ty21a attenuation platform, (iii) the plasmid/cassette specifics (CMV promoter, kan resistance, pMB1 ori, and the 7580 bp pVAX10.VR2-1 sequence), and (iv) the dose regimen constraints (single dose ≤1×10^9 CFU, with dependent ranges ≤1×10^8 or 10^6–10^9, etc.). Legal strength depends on how broadly other members of the same family and later continuations/related patents cover: (a) alternative promoters/cassettes encoding VEGFR-2, (b) alternative dose ranges, (c) other VEGF-pathway targets, and (d) combination regimens (gemcitabine, radiation) with Ty21a/VEGFR-2.

The patent landscape analysis below focuses on claim-scope logic and the typical US enforcement/validity fault lines for this kind of platform-and-dose method claim.

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What patents protect methods using attenuated Salmonella Ty21a delivering VEGFR-2 (SEQ ID NO 1) as a DNA vaccine ≤10^9 CFU?

Core answer. Claim 1 defines the protected method at four technical anchors:

1. Attenuated Salmonella typhi Ty21a (the delivery chassis)
2. An expression cassette encoding human VEGFR-2 with the amino acid identity defined as SEQ ID NO 1
3. Single-dose administration with a numeric CFU limit (≤1×10^9 CFU)
4. Use in cancer immunotherapy broadly (with dependent narrowing to anti-angiogenic and pancreatic cancer).

Claim 1 scope levers (independent)

Claim 1 is structured to cover a method rather than a composition. That matters because direct infringement can occur via use/administration evidence (clinical protocol, drug label instructions, physician administration records, trial methods section). Claim 1 requires all elements simultaneously:

• Patient with cancer (includes metastases per dependent claims)
• Administer a DNA vaccine that is:
  • an attenuated mutant strain of Salmonella typhi Ty21a
  • comprising an expression cassette encoding human VEGFR-2 (SEQ ID NO 1)
• Single dose ≤ 1×10^9 CFU

Dependent claim scope that tightens infringement

• Claim 2: expression cassette must be eukaryotic
• Claim 3: anti-angiogenic context and Ty21a transformed by a plasmid encoding VEGFR-2
• Claim 4: plasmid must be 7580 bp pVAX10.VR2-1 (SEQ ID NO 3)
• Claims 5–7: narrows to pancreatic cancer, including stage IV/locally advanced, and metastases
• Claims 8–10: combination with chemo and/or radiotherapy, including gemcitabine and a timing/cycle concept
• Claims 11–15: oral administration and specific dose selections/ranges
• Claim 16: a method claim that is effectively a VXM01-specific definition of the vaccine construct and dose ceiling.
• Claim 18: expansion to co-administration of other Ty21a mutant strains encoding tumor and/or stromal antigens.

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How broad is US 10,293,037: what does “attenuated mutant strain of Salmonella typhi Ty21a” practically mean for infringement?

Featured-snippet style answer. The wording “attenuated mutant strain of Salmonella typhi Ty21a” ties infringement to a specific platform lineage, not merely any Salmonella delivery system. If an accused product uses Ty21a with substantially different attenuation mutations or a different parental strain, the defense will be to contest whether it is the same “attenuated mutant strain.”

Risk points for generic/platform workarounds

• Switching chassis: using a different attenuated Salmonella strain (even closely related) is a plausible design-around if the patent family does not cover broader “Salmonella delivery” equivalents.
• Genetic attenuation differences: even if Salmonella typhi Ty21a is claimed, courts can require that the accused organism fits the patent’s attenuation definition as construed (often guided by specification, examples, and claim construction history).
• Manufacturing equivalence: dose and identity of the expressed VEGFR-2 product can be the bigger fight; chassis identity may be easier to challenge with strain genotyping and reference maps.

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Which elements of the claim are most likely to be litigated: VEGFR-2 (SEQ ID NO 1), plasmid pVAX10.VR2-1 (SEQ ID NO 3), or the CFU ≤1×10^9 dose?

Most litigated element (typical pattern). For this patent structure, the high-friction issues tend to be:

1. Does the vaccine express the claimed VEGFR-2 protein with the amino acid sequence of SEQ ID NO 1?
2. Is the expression cassette “eukaryotic,” and is it implemented through the claimed plasmid architecture (for narrower dependent claims)?
3. Was the accused dosing protocol a “single dose” at ≤1×10^9 CFU?

VEGFR-2 payload identity

Even if VEGFR-2 is targeted generally, infringement likely hinges on the exact SEQ ID NO 1 sequence. If an accused construct uses:

• a different VEGFR-2 isoform,
• a truncated extracellular domain,
• a codon-optimized variant that changes nucleotide sequence but not protein sequence,
• a signal-peptide altered version that still yields identical amino acid sequence, then infringement may turn on whether the amino acid sequence still matches SEQ ID NO 1. If amino acid identity deviates, design-around is stronger.

Plasmid specificity in dependent claims

• Claim 4 requires pVAX10.VR2-1 and a sequence designation (SEQ ID NO 3). That is a narrower “needle claim.”
• Claim 16 similarly defines VXM01 with: 7580 bp plasmid, CMV promoter, kan resistance, pMB1 ori.
  These elements are precise enough to enable product-by-product validation.

Dose as a numerical limitation

Dose limitations are often enforceable when:

• the protocol instructs a ceiling,
• clinical trial design locks the dose cohorts,
• label/recommendations align to the claimed CFU.
  If an accused regimen exceeds the ceiling or is not “single dose” in the claim sense, the infringement theory may weaken.

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What does “single dose” mean for cancer immunotherapy workflows and how does CFU quantification affect infringement?

Core answer. Claim 1 and claim 16 tie infringement to single-dose administration at ≤1×10^9 CFU. Practically, this requires the accused clinical method to use one administration event (or one dose unit) that is quantified in CFU and stays within the cap.

Quantification/operational friction

• CFU reporting can vary by lot, viability, and assay method. Still, if a protocol specifies “dose levels” in CFU cohorts, those are typically the evidence used in litigation.
• If dosing is fractionated across multiple administrations, defendants may argue it is not a “single dose.”
• If multiple administrations are given (even at lower CFU each), claim scope may not be met unless the “single dose” element is interpreted to cover each individual administration or the method as a whole.

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What formulations are protected: plasmid/cassette requirements and oral administration risks?

Featured snippet answer. The protected “formulation” is the DNA vaccine construct inside the attenuated Ty21a, with specific reliance on a eukaryotic expression cassette encoding VEGFR-2 and, in narrower claims, the pVAX10.VR2-1 plasmid with CMV promoter and other backbone elements.

Oral administration (Claim 11)

• Claim 11 explicitly requires oral administration.
  If an accused therapy delivers via injection route (IV/IM/SC) rather than oral, claim 11 can be avoided.
• If oral is used, route becomes a key factual issue with labeled dosing instructions and trial methods.

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When does US 10,293,037 lose exclusivity: patent term, potential PTA, and key expiration drivers?

Executive summary. Patent expiration is driven by the US filing date (20-year term from earliest non-provisional filing, plus patent term adjustment where granted). Without the actual prosecution/filing timeline and any maintenance payment record, the expiration date cannot be correctly stated here.

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What generic entry risks exist for Ty21a VEGFR-2 DNA vaccine methods: do they qualify as “Paragraph IV” equivalents?

Featured snippet answer. For a method-of-treatment patent like claim 1, “Paragraph IV” is not a direct analogue unless an ANDA applicant challenges an FDA approval that references the drug and the formulation is within an Orange Book framework. For biologics and complex biologics, the equivalent is often BsUFA-related litigation, not ANDA/Paragraph IV.

Method-of-use exposure for follow-on developers

If a follow-on manufacturer uses the same clinical method (dose, route, VEGFR-2 construct), they can face:

• induced infringement theories (training, instructions, label),
• active inducement (protocol enablement),
• contributory theories (supplying the vaccine with instructions for the claimed method).

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What patent litigation affects VEGFR-2 Ty21a DNA vaccine programs, and which parties typically fight?

Critical point. Litigation impact depends on court dockets and patent assertion activity tied specifically to US 10,293,037 and its family. Without docket data, identifying the “challenging companies” or settlement posture would be speculative.

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How do the dependent claims map into commercial development constraints: gemcitabine, radiotherapy cycles, and stage IV pancreatic cancer?

Claims 5–6 and 8–10 narrow the clinical use case to commercial-relevant oncology populations and standard-of-care combinations:

• Pancreatic cancer (stage IV or locally advanced)
• Metastases
• Combination with chemotherapy and/or radiotherapy
• Gemcitabine as chemotherapeutic agent
• Administration “during the chemotherapy treatment cycle” (timing).

Interpretation leverage for infringement or invalidity

• If an accused regimen uses a different chemo backbone (e.g., FOLFIRINOX rather than gemcitabine), it may avoid dependent claim 9 while still risking independent claim 1 if VEGFR-2 Ty21a vaccine dosing is unchanged.
• If timing is different (not “during the cycle” as claimed), dependent claims 10 can be weaker.

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How strong is the patent estate for VEGFR-2 Ty21a DNA vaccine methods: what claim features drive novelty and non-obviousness?

Strength drivers (claim-structure based).

• Specific antigen: human VEGFR-2 by amino acid sequence (SEQ ID NO 1) is narrower than a generic VEGF-pathway concept.
• Platform specificity: Ty21a attenuation chassis is a particular delivery system with known immunostimulatory behavior.
• Dose ceiling: ≤1×10^9 CFU single dose is a numeric limitation that can distinguish from prior art dosing schedules.
• Plasmid identity: pVAX10.VR2-1 sequence (SEQ ID NO 3) and backbone features (CMV promoter, kan resistance, pMB1 ori) constrain dependent claims.

Typical vulnerability patterns

For patents like this, obviousness challenges often argue:

• VEGFR-2 was known as a target in oncology (anti-angiogenic and immunotherapy rationale).
• Ty21a DNA vaccination approaches were known, and altering the expressed antigen is “routine.”
• Dose selection is considered optimization unless tied to unexpected results in the spec. Validity arguments can also target claim clarity issues around “single dose,” oral administration parameters, and whether the expressed VEGFR-2 is functionally expressed in the required manner.

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What formulations are protected by US 10,293,037: VXM01 and pVAX10.VR2-1 definition (Claim 16)

Answer. Claim 16 is the most product-identifying claim:

• Vaccine = VXM01
• Attenuated Salmonella typhi Ty21a transformed by 7580 bp pVAX10.VR2-1
• Plasmid contains DNA encoding VEGFR-2 (SEQ ID NO 1) under CMV promoter
• Contains kanamycin resistance gene and pMB1 ori
• Single dose ≤ 1×10^9 CFU

This claim functions as a “lock” on the exact plasmid and backbone architecture, reducing ambiguity for infringement compared with broader antigen claims.

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Which design-arounds are most plausible against this claim set

Most plausible avoidances map to the four anchors:

1. Payload swap: target a different antigen or VEGFR-2 variant that does not encode the exact SEQ ID NO 1 amino acid sequence.
2. Cassette redesign: even if VEGFR-2 is the same, if the accused product uses a different cassette architecture, claims 2–4 and 16 may be harder to satisfy, though claim 1 may still be asserted if only “expression cassette encoding VEGFR-2 SEQ ID NO 1” is required.
3. Dose regimen: avoid “single dose ≤ 1×10^9 CFU” by exceeding that ceiling or using a different dosing structure that is not a “single dose” as construed.
4. Route: avoid oral administration if claim 11 is the asserted hook.
5. Combination specifics: avoid gemcitabine and timing language to neutralize dependent claims 9–10 while still leaving independent claim 1 exposure if the core Ty21a+VEGFR-2 construct is unchanged.

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Key Takeaways

• US 10,293,037 protects a method of cancer immunotherapy using attenuated Salmonella typhi Ty21a delivering human VEGFR-2 (SEQ ID NO 1) via a eukaryotic expression cassette, with a single-dose cap at ≤1×10^9 CFU.
• The litigation battleground is likely to be payload sequence identity, plasmid/cassette match (especially pVAX10.VR2-1 in narrower claims), and whether the accused regimen stays within the numeric CFU “single dose” limitation.
• Dependent claims add commercial lock-in through anti-angiogenic framing, pancreatic cancer/stage, gemcitabine combination, cycle timing, and oral administration.
• The strongest product-specific protection is in Claim 16, which defines VXM01 and the plasmid backbone elements.

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FAQs

1. If an accused vaccine expresses VEGFR-2 but uses a different VEGFR-2 isoform, does claim 1 still apply?
2. How does splitting dosing into multiple administrations affect the “single dose ≤10^9 CFU” limitation?
3. If the regimen includes gemcitabine but not “during the chemotherapy treatment cycle,” which claims are most exposed?
4. Does oral administration only matter for claim 11, or can it indirectly affect infringement theories for claim 1?
5. What evidence is typically used to prove the presence of a specific plasmid like pVAX10.VR2-1 in an accused product?

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References

(No sources were provided in the prompt, and no reliable patent-bibliography or docket data was included. No citations can be generated without inventing facts.)

Details for Patent 10,293,037

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bavarian Nordic A/s	VIVOTIF	typhoid vaccine live oral ty21a	Capsule	103123	December 15, 1989	10,293,037	2038-05-31