Patent: 10,545,135

Summary for Patent: 10,545,135

Title:	Compositions comprising human embryonic stem cells and their derivatives, methods of use, and methods of preparation
Abstract:	The present invention relates to a pharmaceutical composition comprising of preparations of human embryonic stem (hES) cells and their derivatives and methods for their transplantation into the human body, wherein transplantation results in the clinical reversal of symptoms, cure, stabilization or arrest of degeneration of a wide variety of presently incurable and terminal medical conditions, diseases and disorders. The invention further relates to novel processes of preparing novel stem cell lines which are free of animal products, feeder cells, growth factors, leukaemia inhibitory factor, supplementary mineral combinations, amino acid supplements, vitamin supplements, fibroblast growth factor, membrane associated steel factor, soluble steel factor and conditioned media. This invention further relates to the isolation, culture, maintenance, expansion, differentiation, storage, and preservation of such stem cells.
Inventor(s):	Shroff; Geeta (New Delhi, IN)
Application Number:	12/224,839
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,545,135
Patent Claims:	see list of patent claims

United States Patent 10,545,135: Claim-Critical Review and US Patent Landscape

What does US10,545,135 claim, in enforceable terms?

US Patent 10,545,135 is directed to pharmaceutical compositions and compositions of matter using human embryonic stem (hES) cells and hES-derived progenitors formulated to address three recurring risks in stem-cell products: xeno-free/defined culture absence, tumorigenicity (teratoma) control, and dosing/form factor.

Core independent claim (Claim 1): compositional definition + safety profile + formulation additives

Claim 1 recites a pharmaceutical composition for treating diseases/conditions comprising:

1. Cell payload

   • hES cells, derivatives of hES cells, or both
   • Derivatives are limited to:
     • hematopoietic stem cell progenitors
     • neuronal stem cell progenitors
     • combination of hematopoietic and neuronal stem cell progenitors
     • mesenchymal stem cell progenitors
     • insulin producing stem cell progenitors
     • hepatocytic stem cell progenitors
     • cardiac stem cell progenitors
     • epithelial stem cell progenitors

2. Culture/processing restrictions (xeno-free + defined absence list)

   • The cells are free from:
     • feeder cells
     • animal products
     • growth factors
     • leukemia inhibiting factor (LIF)
     • fibroblast growth factor (FGF)
     • vitamin supplements
     • membrane associated steel factor
     • soluble steel factor
     • conditioned media

3. Tumorigenicity requirement

   • The cells do not give rise to teratomas upon administration

4. Formulation vehicle

   • Cells are suspended in a pharmaceutically acceptable biocompatible solution

5. Specific hormonal additives in trace amounts

   • Composition contains trace amounts of a progestin and a β-human chorionic gonadotrophin (β-hCG) agonist

This combination is the claim’s technical “center of gravity”: it is not just “stem cells for therapy.” It is stem-cell therapy bundled with (i) a defined, feeder-free culture absence and (ii) a specific differentiation/enrichment context (progestin + β-hCG agonist), and (iii) an asserted teratoma safety outcome.

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How broad are the key claim levers, and where are the likely weak points?

1) Patient indication breadth (Claims 16–17)

Claim 16 lists broad disease categories (cancer, stroke, genetic disorders, liver disorders, neuro trauma, autoimmune, eye, kidney, cardiac, arthritis, blood disorders). Claim 17 then enumerates a large set of specific conditions, including:

• Onco: adenocarcinoma, hepatocellular carcinoma, spinal cord tumor, acute myeloid leukemia
• Neuro: Alzheimer’s disease, multiple sclerosis, Parkinson’s, cerebral palsy, Huntington’s chorea, many atrophy/degeneration entries
• Immuno/inflammatory: ulcerative colitis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis
• Endocrine/reproductive: diabetes, fertility disorders, azoospermia, primary ovarian failure, hormone imbalance
• Cardio/vascular: heart failure, coronary artery disease, myocardial infarction, restrictive cardiomyopathy, sinus bradycardia, right bundle branch block
• Others: cystic fibrosis, interstitial lung disease, nephrotic syndrome, thrombocytopenia, thalassemia

Critical enforceability implication: such broad enumerations increase coverage for later regulatory labels, but they also create a high burden for written description/support and a credible linkage between each indication and the claimed formulation/process. A challenger can argue the patent attempts to claim “cells + dosing + culture absence” across disparate clinical use cases without commensurate data per indication.

2) “Teratoma-free” is outcome-based and hard to police

Claim 1 requires that the cells do not give rise to teratomas upon administration.

Critical enforceability implication: “does not give rise” reads like a performance outcome limitation. From a litigation posture, this can cut two ways:

• It can strengthen validity if the patent record shows robust non-tumorigenicity data under relevant administration routes/doses.
• It can weaken infringement certainty if accused products cannot be compared on the same route, dose, immune status, and potency/time horizon.
• It is also vulnerable to “line crossing” if competitors can argue their product has a different undifferentiated fraction, different potency controls, or different persistence in vivo.

3) Xeno-free/defined absence list narrows the preparation history

Claim 1’s “free from” list is extensive and includes specific culture factors (LIF, FGF) and conditioned media. This acts like a manufacturing fingerprint.

Critical enforceability implication: it is likely easier to litigate than “teratoma-free” because manufacturing records and raw material provenance can be examined. Competitors can design around by using different culture components that still yield safe cells, but the patent could still capture them if those components fall outside the enumerated “free from” list or if the claim construction interprets “growth factors” broadly.

4) Progestin + β-hCG agonist is a very specific formulation/process tether

Trace amounts of progestin and β-hCG agonist are required (Claim 1). Dependent Claim 20 specifies the cell expansion medium comprises minimal essential medium + progestin + β-hCG agonist.

Critical enforceability implication: this is likely the most distinctive technical feature. It creates:

• a high relevance for manufacturing control (exact hormonal agents, concentrations, and whether the β-hCG agonist is present as such or via active metabolites),
• potential design-around by using alternative defined media systems without β-hCG agonists.

5) Dose/volume and viability gates add measurement constraints (Claims 4–6, 14–15)

Dependent claims narrow:

• readiness to use (prefilled syringe) (Claim 3)
• sufficient viability (Claim 4)
• viability > 40% (Claim 5)
• saline as solution (Claim 6)
• antimicrobial option (Claim 7)
• cell counts and volumes (Claims 14–15):
  • Claim 14: ~750,000 to ~160 million cells in 0.25 ml to 100 ml
  • Claim 15: ~750,000 to ~80 million cells in 0.25 ml to 10 ml

Critical enforceability implication: these are not universal enough to be met by all stem-cell products. If competitors use cryopreserved logistics, different injection volumes, or different viability acceptance specs, they can avoid certain dependent claims while still potentially infringing Claim 1 depending on claim construction and whether the independent claim reads “suspended in biocompatible solution” without the specific syringe/viability/volume limitation.

6) “No more than 40% undifferentiated stem cells” (Claims 19, 32)

This is an important bridge between cell safety and culture outcome.

Critical enforceability implication: it makes the teratoma assertion less purely qualitative. It creates a quantifiable parameter that can be measured by marker panels or functional assays. It also offers a litigation lever: if the accused product’s undifferentiated fraction is provably above or below the 40% threshold under comparable gating/assay, infringement or invalidity theories can sharpen.

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How do composition-of-matter claims differ (Claim 25 onward)?

Claim 25 recites a composition of matter with additional delivery-structure features:

• Cells are entrapped in a biocompatible selectively permeable structure or matrix
• Matrix select list includes broad material classes: biopolymers, polypeptides, proteins, polysaccharides, and specific examples including agarose, gelatin, collagen, laminin, fibronectin, and others
• Dependent Claim 30 limits examples: agarose + collagen or agarose + gelatin
• It retains the same critical pillars: feeder-free/xeno-free/absence list, teratoma-free, and trace progestin + β-hCG agonist

Critical enforceability implication: this claim scope likely captures a specific formulation concept (encapsulation/entrapment with selective permeability) rather than injection suspension alone. A competitor can potentially avoid by using a different device architecture (e.g., not selectively permeable entrapment, or different matrix materials outside claim lists, or a non-entrapped injectable formulation).

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What is the most enforceable “core” versus the easiest-to-design-around features?

Most enforceable (hard to move without giving up claim structure)

1. “Free from” culture absence list (feeder cells, animal products, growth factors, LIF, FGF, vitamin supplements, steel factors, conditioned media)
2. Teratoma non-occurrence limitation
3. Trace progestin + β-hCG agonist requirement
4. Derivative categories (specific progenitor types)

Easiest to design around (often shifted in manufacturing)

1. Matrix entrapment for Claim 25-type protection (if competitors use direct suspension or different delivery constructs)
2. Prefilled syringe and saline-only limitations (dependent claims)
3. Viability > 40% and specific cell dose/volume ranges (dependent claims)
4. Undifferentiated fraction cap at 40% is measurable but also potentially adjustable via differentiation protocols and potency specs

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US patent landscape: what kinds of competing filings will most likely collide with US10,545,135?

The landscape for hES-derived therapies tends to cluster around:

• differentiation media and feeder-free manufacturing platforms,
• safety claims focusing on undifferentiated cell control and teratoma risk,
• formulation/delivery systems (encapsulation matrices, device-based delivery),
• cell types and targeted lineage-specific progenitors for particular indications.

US10,545,135 is unusually “process-coupled,” so the closest conflicts typically arise where other patents claim defined, feeder-free differentiation and specific medium components that overlap with progestin + β-hCG agonist, or where they claim xeno-free, growth-factor-free progenitor preparations with quantified undifferentiated fraction limits.

Likely collision zones (by claim element)

A. Media composition and hormones

• Patents claiming hES expansion/differentiation using defined media without feeders and without animal components will overlap on:
  • feeder-free and xeno-free features
  • absence of conditioned media and certain growth factors
• Overlap strengthens if the competing patent uses progestin and/or β-hCG agonists.

B. Teratoma safety and undifferentiated limits

• Patents that claim:
  • potency assays limiting undifferentiated cells,
  • non-tumorigenicity evidence,
  • purity thresholds (marker-based or functional) will collide with Claims 1, 19, 32.

C. Delivery/formulation

• Patents claiming encapsulation/entrapped cell delivery with selectively permeable matrices collide with Claims 25, 29, 30.
• Patents focusing on injectable suspensions with saline/ready-to-use form can collide only with dependent claims (2–4, 6, 14–15, depending on exact constraints).

D. Lineage progenitor categories

• Patents claiming hES-derived:
  • hematopoietic, neuronal, mesenchymal, insulin-producing, hepatocytic, cardiac, epithelial progenitors will collide on the derivative list even if their differentiation platform differs, unless they add media components that avoid the “free from” limitations.

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What is the critical competitive risk for companies developing hES-derived cell products?

Risk 1: Process entrapment through “free from” media exclusions

If a competitor uses feeder-free, xeno-free culture but still uses any factor deemed to fall within “growth factors,” “vitamin supplements,” “FGF,” or “steel factors,” they may still be within the claim depending on claim interpretation. A competitor that wants clean freedom-to-operate typically needs a manufacturing platform that either:

• includes explicit components outside the enumerated “free from” list while still meeting overall safety, or
• is built so that it cannot be argued to be “free from” any category the court construes broadly.

Risk 2: Outcome-based safety (teratoma)

Even if a competitor avoids the exact media ingredients, it can still face disputes around:

• undifferentiated fraction measurement
• in vivo tumorigenicity under relevant models

Risk 3: Progestin + β-hCG trace addition as a “litigation magnet”

The progestin/β-hCG trace requirement is likely the most direct differentiator. If any competing platform uses these hormones at any stage such that the final composition contains them as traces, that platform can become high-risk on Claim 1 and Claim 25.

Risk 4: Device/form factor and encapsulation

Encapsulation in selectively permeable matrices is a narrow technical channel but can still be a major selling point. It is an easy commercial feature to adopt, but it can also be an easy IP collision if competitors reuse similar materials and structure concepts.

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Operational takeaways for FTO and R&D positioning

Claim-targeted design-around options

1. Avoid the final composition containing trace progestin + β-hCG agonist

   • Ensure the final drug product does not contain those agents as traces, if that is manufacturing-feasible without harming differentiation and safety.

2. Avoid being “free from” broad categories as construed by the patent

   • If the patent construes “growth factors” broadly, then using an alternative defined system may be needed.
   • If it construes “vitamin supplements” broadly, then standard defined media supplements could create overlap risk.

3. Change delivery architecture

   • Use direct suspension outside an entrapped selectively permeable matrix to avoid Claim 25-family coverage.

4. Move dosing out of dependent ranges

   • If cell counts and injected volumes are kept outside the dependent ranges, that may preserve Claim 1 exposure though it can reduce dependent claim infringement.

5. Quantify undifferentiated fraction and teratoma risk under comparable regimens

   • If product potency release and in vivo safety can show compliance with a different undifferentiated threshold or a different risk profile, the “teratoma-free” limitation becomes harder for a patentee to enforce against you.

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Key Takeaways

• US10,545,135’s enforceability hinges on a tight coupling of hES-derived progenitors with defined feeder-free/xeno-free manufacturing exclusions plus teratoma non-occurrence, and it requires the final composition to include trace progestin + β-hCG agonist.
• The patent’s broad disease list increases commercial relevance but also creates a litigation angle around whether the patent record supports broad indication coverage with commensurate evidence.
• Design-around is most likely through breaking at least one of the core constraints: β-hCG/progestin presence in the final product, the “free from” processing exclusions as construed, or the delivery architecture (entrapped selectively permeable matrix).
• Dependent claims (prefilled syringe, saline vehicle, viability > 40%, dose ranges, ≤40% undifferentiated fraction) are measurable and offer additional non-uniform infringement surfaces.

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FAQs

1) What is the single most distinctive technical requirement in US10,545,135?

Trace amounts of progestin and a β-hCG agonist in the final composition, tied to defined expansion/differentiation context (Claim 1; Claim 20).

2) Does the patent claim any specific manufacturing system beyond media absence?

Yes. It locks in an expanded media context via Claim 20 (minimal essential medium + progestin + β-hCG agonist) and defines extensive “free from” restrictions (Claim 1).

3) How does US10,545,135 handle safety against teratomas?

It requires that hES cells and derivatives do not give rise to teratomas upon administration (Claim 1), with a quantifiable dependent safeguard of ≤40% undifferentiated stem cells (Claims 19, 32).

4) Is the delivery form critical?

For Claim 25 and related claims, yes. It requires entrapped cells in a selectively permeable biocompatible matrix (Claim 25; Claims 29–30). Claim 1 is a suspension formulation.

5) Which dependent claims most affect day-to-day product design?

Viability threshold (>40%, Claim 5), dosing ranges and injection volumes (Claims 14–15), and device/ready-to-use constraints like prefilled syringe (Claim 3).

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References

[1] United States Patent No. 10,545,135. Claims text as provided in the prompt.

Details for Patent 10,545,135

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bavarian Nordic A/s	RABAVERT	rabies vaccine	For Injection	103334	October 20, 1997		2027-03-06
Sanofi Pasteur Sa	IMOVAX RABIES	rabies vaccine	For Injection	103931	February 04, 2000		2027-03-06