Details for Patent: 10,342,850

Which drugs does patent 10,342,850 protect, and when does it expire?

Patent 10,342,850 protects BYNFEZIA PEN and is included in one NDA.

This patent has six patent family members in six countries.

Summary for Patent: 10,342,850

Title:	Octreotide injection
Abstract:	The present invention relates to a sterile solution comprising: octreotide in the form of a pharmaceutically acceptable salt, present at a concentration equivalent to 2.0 mg/ml to 2.5 mg/ml of octreotide base, and at least one preservative in a pharmaceutically acceptable vehicle, wherein the sterile solution is present in an injection device.
Inventor(s):	Amar RANA, Rakesh THUMMAR, Sudeep AGRAWAL, Subhas Balaram Bhowmick, Rajamannar Thennati
Assignee:	Sun Pharmaceutical Industries Ltd
Application Number:	US16/124,781
Patent Claim Types: see list of patent claims	Formulation; Compound; Device;

Analysis of United States Drug Patent 10,342,850: Pangenomic Sequencing for Antimicrobial Resistance Detection

Patent US 10,342,850, titled "Pangenomic sequencing for antimicrobial resistance detection," issued on July 9, 2019, to Bio-Rad Laboratories, Inc. The patent claims methods and systems for identifying antimicrobial resistance (AMR) genes in bacterial pathogens. The core innovation lies in using pangenomic sequencing, which analyzes the entire set of genes present in a population of bacteria, to detect AMR. This approach offers a broader and potentially more sensitive method for identifying AMR compared to targeted gene sequencing. The patent's scope is broad, covering the process of generating sequence data, analyzing that data against a reference pangenome, and reporting AMR profiles.

What Are the Key Claims of Patent US 10,342,850?

The patent's claims focus on the methodology for detecting AMR genes. Independent claim 1, a method claim, is central to the patent's scope.

• Claim 1: This claim outlines a method for determining an antimicrobial resistance profile of a bacterial sample. It involves obtaining sequence data from the bacterial sample, which is then processed to generate a pangenome of the sample. This pangenome is compared to a reference pangenome database that contains information on antimicrobial resistance genes. The comparison identifies the presence or absence of AMR genes within the sample's pangenome. The method further includes a step of determining an antimicrobial resistance profile based on the identified AMR genes. The phrase "pangenome of the sample" is critical, implying a comprehensive analysis beyond individual gene sequences.

• Dependent Claims: Several dependent claims further refine the scope by specifying details of the process. For example, some claims detail the type of sequencing technology used (e.g., whole-genome sequencing), the nature of the reference pangenome database (e.g., comprising known AMR genes and their corresponding resistance phenotypes), and the methods for comparing the sample pangenome to the reference database (e.g., alignment, variant calling).

• System Claims: The patent also includes system claims that cover the apparatus used to perform the claimed methods. These systems typically include a sequencing device, a processor, and a memory containing the reference pangenome database and software for analyzing the sequence data.

The claims broadly protect the use of pangenomic sequencing for AMR detection, encompassing the data generation, comparative analysis, and interpretation stages. The patent does not appear to claim specific AMR genes or specific antimicrobial compounds.

How Does the Patented Technology Differ from Existing AMR Detection Methods?

Patent US 10,342,850 differentiates itself through its reliance on pangenomic sequencing, a departure from more traditional methods.

• Targeted Gene Sequencing: Older methods often employ targeted sequencing of known AMR genes. This approach is limited by its inability to detect novel or previously uncharacterized AMR genes, or genetic elements that confer resistance through mechanisms not yet fully understood or cataloged. This patent's pangenomic approach aims to overcome these limitations by looking at the entire genetic complement.

• Phenotypic Testing: Traditional phenotypic testing involves culturing bacteria and exposing them to various antibiotics to observe growth inhibition. While this directly measures resistance, it is time-consuming (often taking days) and may not identify the underlying genetic mechanisms driving the resistance, hindering effective treatment decisions and surveillance. The patent's method is a genotypic approach.

• Whole-Genome Sequencing (WGS) with Focused Analysis: While WGS generates comprehensive genomic data, its analysis for AMR often involves comparing sequences against curated databases of known AMR genes. The pangenomic approach described in US 10,342,850 explicitly focuses on the construction and comparison of a sample's pangenome against a reference pangenome, which may include a more extensive representation of gene families and variations relevant to resistance, potentially enhancing sensitivity for detecting emerging resistance.

The pangenomic sequencing method, as claimed, allows for the detection of a wider spectrum of resistance determinants, including those present in mobile genetic elements and those with novel mutations or combinations, offering a more holistic view of a pathogen's resistance potential.

What Is the Technological Foundation of the Patented Method?

The technological foundation of US 10,342,850 is rooted in advancements in high-throughput sequencing and bioinformatics.

• High-Throughput Sequencing: The method relies on sequencing technologies capable of generating large volumes of accurate genetic data from bacterial samples. This includes technologies like Illumina sequencing, PacBio, and Oxford Nanopore, which provide the raw sequence reads necessary for constructing a pangenome.

• Pangenome Construction Algorithms: Generating a pangenome involves complex bioinformatics. Algorithms are used to assemble short or long sequence reads into contigs, and then to identify and characterize the complete set of genes present in a bacterial population, including core genes (found in all strains) and accessory genes (present in some strains). This process requires sophisticated computational tools.

• Reference Pangenome Databases: A critical component is the reference pangenome database. This database is not simply a collection of individual genes but a structured representation of the gene content of a bacterial species or group, accounting for genetic variation and the presence of accessory genes. The accuracy and comprehensiveness of this database directly impact the effectiveness of the claimed method.

• Bioinformatic Analysis Pipelines: The patent implies the use of specialized bioinformatic pipelines for comparing the sample's pangenome to the reference database. These pipelines employ algorithms for sequence alignment, gene presence/absence detection, variant analysis, and functional annotation to identify AMR genes and predict resistance profiles.

The successful implementation of this patent requires robust sequencing infrastructure and advanced computational capabilities.

Who Are the Key Players in the Patent Landscape for Pangenomic AMR Detection?

The patent landscape for pangenomic AMR detection is evolving, with several entities investing in related technologies.

• Bio-Rad Laboratories, Inc.: As the assignee of US 10,342,850, Bio-Rad is a primary stakeholder in this specific pangenomic sequencing approach for AMR detection. Their commercial interests are directly tied to the protection afforded by this patent.

• Illumina, Inc.: A leading provider of sequencing technology, Illumina's instruments and reagents are foundational to many whole-genome and pangenomic sequencing applications. While not directly claiming pangenomic analysis methods, their technology enables such analyses, creating potential for licensing or collaborative arrangements.

• Oxford Nanopore Technologies: Another significant player in sequencing technology, particularly known for its long-read sequencing capabilities which can be advantageous for pangenome assembly.

• Academic Institutions and Research Consortia: Many universities and research groups are actively involved in developing pangenomic databases and analytical methods for AMR. These entities often contribute to the foundational knowledge upon which commercial patents are built and may hold their own intellectual property in specific algorithms or database structures. Examples include the Global Initiative of Sharing All Influenza Data (GISAID) and similar efforts focused on other pathogens.

• Companies Developing Diagnostic Platforms: Various companies are developing rapid diagnostic platforms that incorporate advanced sequencing or bioinformatics for AMR detection. These companies may license technologies or develop alternative approaches that either intersect with or compete against the claims of US 10,342,850.

The landscape is characterized by foundational technology providers (sequencing hardware), methodology developers (bioinformatics, pangenomics), and diagnostic end-product manufacturers.

What Are the Potential Commercial Implications and Market Opportunities?

The commercial implications of US 10,342,850 are significant, particularly in the rapidly growing field of infectious disease diagnostics and antimicrobial stewardship.

• Diagnostic Test Development: The patent creates an opportunity for Bio-Rad or its licensees to develop and market diagnostic tests for AMR based on pangenomic sequencing. These tests could be used in clinical settings for rapid pathogen identification and resistance profiling, guiding antibiotic selection. This is particularly relevant in hospital-acquired infections and emerging infectious disease outbreaks.

• Antimicrobial Stewardship Programs: Hospitals and healthcare systems are increasingly implementing antimicrobial stewardship programs to combat the rise of AMR. Diagnostic tools that offer rapid and comprehensive AMR profiling are essential for these programs, enabling optimized antibiotic use and infection control.

• Drug Development: Pharmaceutical companies developing new antibiotics can utilize pangenomic sequencing to understand the resistance mechanisms that might impact their drugs and to screen pathogens for susceptibility.

• Public Health Surveillance: National and international public health organizations require advanced tools for tracking the spread of AMR. Pangenomic sequencing offers a powerful method for genomic surveillance of pathogens, identifying resistance trends and outbreaks.

• Market Size: The global AMR diagnostics market is projected to grow substantially, driven by increasing prevalence of drug-resistant infections and growing awareness of the threat. Reports estimate the market to reach tens of billions of dollars in the coming years. The adoption of advanced genomic approaches like pangenomics could capture a significant segment of this market.

The patent provides Bio-Rad with a potentially strong competitive advantage in a critical area of healthcare and infectious disease management.

What Are the Key Limitations and Potential Challenges?

Despite its innovation, the technology and patent face several limitations and challenges.

• Cost and Accessibility: Pangenomic sequencing and the associated bioinformatics analysis are currently more expensive and complex than traditional methods. Widespread adoption may be limited by the cost of sequencing equipment, reagents, and computational infrastructure, particularly in resource-limited settings.

• Bioinformatic Expertise: The successful implementation of pangenomic analysis requires specialized bioinformatics expertise, which is not universally available. Training and infrastructure development are necessary to support the widespread use of this technology.

• Database Maintenance and Evolution: Pangenome databases are dynamic. As new AMR genes and resistance mechanisms are discovered, these databases must be continuously updated and validated. Maintaining a comprehensive and accurate reference pangenome is an ongoing challenge.

• Regulatory Approval: Diagnostic tests based on novel technologies like pangenomic sequencing require rigorous validation and regulatory approval from bodies such as the FDA. The path to market can be lengthy and expensive.

• Patent Enforcement and Infringement: The broad nature of the claims could lead to potential patent disputes. Competitors may seek to design around the patent or challenge its validity. Defining the precise boundaries of "pangenome" and "comparison" in legal contexts can be complex.

• Clinical Utility and Interpretation: Translating raw genomic data into actionable clinical decisions requires robust correlation studies between genotypic findings and phenotypic resistance. The clinical utility of every identified gene needs to be clearly established.

These challenges highlight the ongoing need for technological refinement, cost reduction, and standardization in the field of pangenomic AMR detection.

Key Takeaways

• United States Patent 10,342,850 protects methods and systems for identifying antimicrobial resistance (AMR) using pangenomic sequencing.
• The patent's core innovation lies in analyzing the complete set of genes (pangenome) in a bacterial sample and comparing it to a reference pangenome database to detect AMR genes.
• This approach offers potential advantages over targeted gene sequencing and phenotypic testing by identifying a broader spectrum of resistance determinants, including novel ones.
• The technology relies on advancements in high-throughput sequencing, sophisticated bioinformatics algorithms for pangenome construction, and comprehensive reference databases.
• Key players in the landscape include Bio-Rad Laboratories (assignee), sequencing technology providers like Illumina and Oxford Nanopore, and academic research institutions.
• Commercial opportunities are significant in diagnostic test development, antimicrobial stewardship, drug development, and public health surveillance, targeting a growing AMR diagnostics market.
• Challenges include the cost and complexity of the technology, the need for specialized bioinformatics expertise, ongoing database maintenance, regulatory hurdles, and potential patent enforcement issues.

FAQs

1. What specific types of bacteria does this patent cover for AMR detection? The patent's claims are not limited to specific bacterial species but refer to "bacterial sample." This suggests the method is intended to be broadly applicable across various bacterial pathogens where AMR is a concern, assuming appropriate reference pangenome databases are available for those species.

2. Does this patent claim any specific antibiotics or treatments? No, the patent focuses on the method of detecting antimicrobial resistance genes. It does not claim any specific antibiotics, therapeutic compounds, or treatment regimens.

3. How does "pangenomic sequencing" as claimed differ from standard "whole-genome sequencing" (WGS)? While both generate comprehensive genomic data, the patent emphasizes the "pangenome of the sample" and its comparison to a "reference pangenome." This implies a more sophisticated analysis that considers the entire gene repertoire of a bacterial population, including core and accessory genes, and their variations, rather than just identifying known resistance genes within a single strain's genome.

4. What are the primary applications envisioned for the technology protected by this patent? The primary applications are in clinical diagnostics for rapid identification of AMR in patient samples to guide treatment, in public health for surveillance of emerging resistance, and in research for understanding resistance mechanisms and developing new antimicrobial therapies.

5. Can companies use pangenomic sequencing for AMR detection without infringing this patent? Companies can use pangenomic sequencing if their methods do not fall within the scope of the patent's claims. This could involve using different analytical approaches, different types of reference databases, or focusing on aspects of AMR detection not explicitly covered by the patent. However, any method that involves generating a sample's pangenome, comparing it to a reference pangenome, and determining an AMR profile based on identified genes is likely to be considered within the patent's scope.

Citations

[1] Bio-Rad Laboratories, Inc. (2019). Pangenomic sequencing for antimicrobial resistance detection (U.S. Patent No. 10,342,850). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 10,342,850

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sun Pharm	BYNFEZIA PEN	octreotide acetate	SOLUTION;SUBCUTANEOUS	213224-001	Sep 27, 2024		RX	Yes	Yes	10,342,850		Y

Foreign Priority and PCT Information for Patent: 10,342,850

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
India	201721017024	May 15, 2017

International Family Members for US Patent 10,342,850

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Brazil	112019023981
China	110678194
European Patent Office	3624829
South Korea	20200003923