How to Make Many Copies of a DNA Piece with Heat
This patent describes the Polymerase Chain Reaction (PCR) method, a technique to make millions of copies of a specific DNA segment using a heat-resistant enzyme and repeated temperature changes.
Original patent title: “Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme”
This patent describes the Polymerase Chain Reaction (PCR) method, a technique to make millions of copies of a specific DNA segment using a heat-resistant enzyme and repeated temperature changes. Granted to Cetus Corp in 1990 with 60 claims and 2,132 forward citations.
Key facts
Coverage
What does this patent actually cover?
The patent describes the core steps of the Polymerase Chain Reaction (PCR). It involves taking a DNA sample and adding building blocks called nucleoside triphosphates, short starting pieces called oligonucleotide primers, and a special heat-resistant enzyme (a "thermostable enzyme"). First, the DNA strands are separated by heating the mixture (claimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1(d)). Then, the mixture is cooled so the primers can attach to their specific spots on the single DNA strands (claim 1(e)). Next, the enzyme builds new DNA strands starting from these primers (claim 1(f)). This cycle of heating, cooling, and building is repeated many times, creating a huge number of copies of the target DNA sequence. For example, a tiny blood sample from a crime scene can be amplified to get enough DNA for forensic analysis.
The gap
What does this patent NOT cover?
- Amplification methods that do not use a thermostable enzyme, as claimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1(b) specifically requires a "thermostable enzyme."
- Processes that do not involve repeated cycles of heating to separate DNA strands and cooling for primer binding and extension, as described in claimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1(d), (e), and (f).
- Methods that do not use two oligonucleotide primers for each specific sequence being amplified, as claimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1(a) specifies "two oligonucleotide primers."
- Amplification of RNA directly without first converting it to DNA, as claimclaimA numbered sentence at the end of a patent that legally defines what the inventor owns. The most important section.Read more → 1 primarily focuses on amplifying "DNA or a mixture of nucleic acids."
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
What made this novel
The key innovation was combining the known principles of DNA replication with a *thermostable* enzyme. This allowed the reaction mixture to be heated to separate DNA strands without destroying the enzyme, meaning fresh enzyme didn't need to be added in each cycle, making the process efficient and automatable.
Schematic visualization of the patent's claim structure. Hand-drawn diagrams in progress for each landmark patent.
Where you've seen this
Real-world examples
COVID-19 diagnostic tests
Forensic DNA analysis (e.g., crime scene investigation)
Paternity testing
Genetic disease screening
Gene cloning
Archaeological DNA studies
Why it matters
The bigger picture
This patent describes the fundamental process of Polymerase Chain Reaction (PCR), a technique that revolutionized molecular biology and biotechnology. It enabled scientists to quickly and efficiently make millions of copies of specific DNA sequences from tiny samples. This capability became essential for genetic research, disease diagnosis, forensic science, and paternity testing, making previously impossible analyses routine.
Filed
June 17, 1987
Granted
October 23, 1990
Market context
Who's building on this
Companies in this space
Companies like Thermo Fisher Scientific, Bio-Rad Laboratories, and Roche Diagnostics continue to develop and sell PCR machines, reagents, and kits. Newer companies are also building on PCR by developing faster, more portable, or more sensitive PCR-based diagnostic tools for various applications, including point-of-care testing.
Market impact
The invention of PCR created an entirely new market for molecular diagnostic tools and research reagents. It enabled the rapid growth of biotechnology, making it possible to analyze DNA with unprecedented speed and sensitivity. This led to a boom in genetic testing, forensic science, and the development of new therapies, fundamentally changing how biological research and medical diagnostics are conducted.
Claim 1 — Plain English
What this patent covers
The patent describes the core steps of the Polymerase Chain Reaction (PCR). It involves taking a DNA sample and adding building blocks called nucleoside triphosphates, short starting pieces called oligonucleotide primers, and a special heat-resistant enzyme (a "thermostable enzyme"). First, the DNA strands are separated by heating the mixture (claim 1(d)). Then, the mixture is cooled so the primers can attach to their specific spots on the single DNA strands (claim 1(e)). Next, the enzyme builds new DNA strands starting from these primers (claim 1(f)). This cycle of heating, cooling, and building is repeated many times, creating a huge number of copies of the target DNA sequence. For example, a tiny blood sample from a crime scene can be amplified to get enough DNA for forensic analysis.
The clever bit
The key innovation was combining the known principles of DNA replication with a *thermostable* enzyme. This allowed the reaction mixture to be heated to separate DNA strands without destroying the enzyme, meaning fresh enzyme didn't need to be added in each cycle, making the process efficient and automatable.
What it does not cover
- Amplification methods that do not use a thermostable enzyme, as claim 1(b) specifically requires a "thermostable enzyme."
- Processes that do not involve repeated cycles of heating to separate DNA strands and cooling for primer binding and extension, as described in claim 1(d), (e), and (f).
- Methods that do not use two oligonucleotide primers for each specific sequence being amplified, as claim 1(a) specifies "two oligonucleotide primers."
- Amplification of RNA directly without first converting it to DNA, as claim 1 primarily focuses on amplifying "DNA or a mixture of nucleic acids."
Patent timeline
Application submitted to the patent office
Application published, typically 18 months after filing
Patent officially issued
PatentBrief Score
Impact Score
Strong
Citation count
40/40
Highly cited
Claim breadth
20/20
Very broad protection
Recency
0/20
Older than 20 years
Assignee scale
0/20
Independent or smaller assigneeassigneeThe entity that owns the patent — usually the inventor's employer or a company.Read more →
PatentBrief Impact Score — based on citation count, claim breadth, recency, and assignee scale. Not a legal assessment.
Heuristic Value Estimate
What this patent might be worth
$216K – $691K
Midpoint $432K · expired or expiring · industry ×3.0
Heuristic only — blends forward/backward citation counts, claim scope, time remaining, litigation history, and CPC-derived industry baseline. Real valuations need a professional appraisal.
The original legal language
Original claims
60 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Saiki, R. K., Mullis, K. B., Gelfand, D. H., Erlich, H. A., & Horn, G. (1990). How to Make Many Copies of a DNA Piece with Heat (U.S. Patent No. 4,965,188). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/4965188/taq-polymerase-for-pcr
Auto-generated from the patent record. Double-check author order and the issue date against the official USPTO document before submitting.
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Common Questions
Frequently Asked Questions
What does How to Make Many Copies of a DNA Piece with Heat cover?
This patent describes the Polymerase Chain Reaction (PCR) method, a technique to make millions of copies of a specific DNA segment using a heat-resistant enzyme and repeated temperature changes.
Who owns patent US 4965188?
Cetus Corp owns this patent, granted in 1990.
When does this patent expire?
This patent has expired and is now in the public domain — anyone can use the invention freely.
What is patent US 4965188 cited by?
This patent has been cited by 2132 later patents that build on its ideas.
What problem does this patent solve?
This patent describes the fundamental process of Polymerase Chain Reaction (PCR), a technique that revolutionized molecular biology and biotechnology. It enabled scientists to quickly and efficiently make millions of copies of specific DNA sequences from tiny samples. This capability became essential for genetic research, disease diagnosis, forensic science, and paternity testing, making previously impossible analyses routine.
What does this patent NOT cover?
Amplification methods that do not use a thermostable enzyme, as claim 1(b) specifically requires a "thermostable enzyme."
Same assignee
More from Cetus Corp
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