Third Wave Technologies, Inc. v. Stratagene Corp. (381 F. Supp. 2d 891, 2005)

OPINION AND ORDER

CRABB, District Judge.

In this civil action, plaintiff Third Wave Technologies, Inc. contends that defendant Stratagene Corporation infringed claims 1, 5, 7, 12 and 14 of plaintiffs U.S. Patent No. 6,348,314 (the ’314 patent) and claim 16 of plaintiffs U.S. Patent No. 6,090,543 (the ’543 patent), both of which relate to cleavage of nucleic acids, by making, using, importing, offering for sale and selling its FullVelocity™ products. Plaintiff seeks declaratory, injunctive and monetary relief under 35 U.S.C. § 271. Defendant asserts four counterclaims, seeking declarations of non-infringement and invalidity of the two patents. The case is before the court on plaintiffs motion for summary judgment on the issue of infringement. Jurisdiction is present. 28 U.S.C. §§ 1331 and 1338(a).

Although the parties have raised a host of arguments, their, primary dispute is whether the mutant Pfu polymerase enzyme employed by defendant’s products prevents the two oligonucleotides claimed in the patents from defining contiguous regions on the target nucleic acid, as required in both patents. Defendant argues that the physical space occupied by the polymerase prevents the establishment of contiguity. Although plaintiff has submitted evidence suggesting that the Pfu polymerase dissociates from the structure prior to cleavage, it has not attempted to show that the physical space once occupied by the polymerase left vacant after dissociation fills in or closes up, either by the addition of new nucleotides or by re-annealing of the oligonucleotide that the polymerase had displaced. Because I find the evidence on the question of contiguity to be inconclusive, plaintiffs motion will be denied.

From the parties’ proposed findings of fact, I find the following to be material and undisputed.

UNDISPUTED FACTS

A. The Parties

Plaintiff Third Wave Technologies is a Delaware corporation with its principal place of business in Madison, Wisconsin. Plaintiff is the owner by valid assignment of U.S. Patent No. 6,348,314 (the ’314 patent) and U.S. Patent No. 6,090,543 (the ’543 patent). Defendant Stratagene Corporation is a Delaware corporation with its principal place of business in La Jolla, California. Defendant manufactures and sells biological products including FullVelocity™ QPCR Master Mix and FullVelocity™ QRT-PCR Master Mix, both of which are designed for probe-based detection of nucleic acids. (I will refer to the FullVelocity™ QPCR Master Mix and FullVelocity™ QRT-PCR Master Mix collectively as the “FullVelocity™ products,” ignoring the other products in defendant’s FullVelocity™ line that are not accused of infringement.) On September 15, 2004, plaintiff brought this suit against defendant, contending that the FullVelocity™ products infringe both the ’314 and ’543 patents.

B. Background Technology

With the exception of bacteriophage, DNA viruses and RNA viruses, all living things contain genetic information in one or more long molecules known as chromosomes. Each chromosome comprises a number of subunits called genes, which are composed of deoxyribonucleic acid, DNA, that encodes the information necessary for cells to reproduce and to produce specific proteins critical to sustaining life. On the molecular level, DNA consists of two long chains or strands that wrap around each other in a shape commonly referred to as a double helix, which can be visually conceptualized as a twisted ladder. In diameter, the double helix is approximately 70 angstroms long, with an angstrom being one hundred millionth of a centimeter.

The building blocks for each strand are called nucleotides, each consisting of a sugar group, a phosphate group and a base. The sugar and phosphate groups are constant and form the sides of the ladder. The rungs of the ladder are made of pairs of bases, one from each of the two DNA strands. There are four different bases found in DNA: adenine, or A; guanine, G; cytosine, C; and thymine, T. Nucleotides are identified according to the type of base they contain. Each rung is separated by 3.4 angstroms. Typically, an oligonucleo-tide is defined as a single strand of DNA (not in a double helix) made up of a few nucleotides; the term polynucleotide is commonly used to refer to a strand with many nucleotides.

A single strand of DNA can be graphically represented by listing the order of bases in that strand, e.g., A-T-G-C-C-GT-A. The genetic information contained in each DNA molecule is conveyed according to the sequence of nucleotides. Because particular errors in genetic sequences have been correlated with a number of significant diseases, much scientific research has been devoted to identifying and detecting nucleotide sequences that cause disease or affect the treatment of disease.

1. Hybridization

The process by which two strands of DNA come together is called hybridization and can be visualized as the closing of a zipper. Hybridization occurs under certain reaction conditions when the sequences of bases in two strands of DNA are sufficiently complementary. For reasons having to do with the chemical composition of each of the bases, A prefers to pair with its complement T and C prefers to pair with its complement G. Thus, a strand of DNA with the sequence AACGATGC will prefer to hybridize with a second strand containing the sequence TTGCTACG. A can also pair with the base uracil, U, which is found in nature in ribonucleic acid (RNA). RNA is similar to DNA except in the type of sugar found in each nucleotide and the inclusion of the base uracil (U) in place of thymine (T). In artificial systems, U can be used in DNA instead of T. The phenomenon of complementary base pairing makes it possible to infer the order of nucleotides found on one strand of DNA from the order of nucleotides on the other side. In other words, if the sequence of one strand of DNA is known, the sequence on a fully complementary strand can be deduced. The known sequence is referred to as the probe, the unknown sequences is called the target.

Each strand of DNA has two ends: a 5' end (pronounced “five prime”) and a 3' end (pronounced “three prime”). The sugar group in each nucleotide has a 5' hydroxyl group and a 3' hydroxyl group. The 3' hydroxyl group of one nucleotide connects to the 5' hydroxyl group of the adjoining sugar. At one end of a DNA strand is a nucleotide with an unconnected 5' hydrox-yl group and at the other end, a nucleotide with an unconnected 3' hydroxyl group. The end of a DNA strand with an unconnected 5' hydroxyl group is the 5' end and the opposite end is the 3' end. The two strands making up a double helix hybridize in “anti-parallel” fashion. This means that if one were to draw an arrow from the 3' end toward the 5' end for each of the two strands, the two arrows would be pointing in opposite directions. By convention, a feature on a DNA strand that is in the 5' direction from a second feature on the same strand is referred to as being “upstream” of the second feature; a feature in the 3' direction is referred to as being “downstream” of the second feature. Thus, when two oligonucleotides hybridize to a single nucleic acid molecule so that the 5' end of one oligonucleotide is upstream of the 5' end of the other, the first oligonu-cleotide is known as the “upstream oligo-nucleotide” and the other as the “downstream oligonucleotide.”

2. DNA replication and polymerases

When a cell reproduces or divides, its DNA copies itself in a process called DNA replication. During replication, the two strands of DNA separate from each other through a process referred to as de-naturation and each serves as a template for a newly synthesized complementary strand of DNA. DNA replication is facilitated by enzymes, which are protein-based molecules that catalyze certain biochemical reactions, including the replication and manipulation of genetic information. Different types of enzymes vary in the type of reactions they catalyze, the temperature at which they function and the substances upon which they react. Enzymes that work at elevated temperatures are said to be thermostable.

Of particular importance in DNA replication are polymerase enzymes. Polymerases create DNA strands that are complementary to a template strand by generating one complementary nucleotide at a time. Polymerization takes place in a pocket sometimes called an active site within the polymerase. Occasionally, polymerases insert a non-complementary nucleotide, which is known as a mismatch. Polymerization occurs in a directional manner: a polymerase moves upstream along the target and adds nucleotides to the 3' end of the newly created strand. When certain types of polymerase enzymes encounter an oligo-nucleotide annealed to the template, they displace this oligonucleotide one nucleotide at a time to make way for the extending strand.

3. DNA cleavage and nucleases

A nuclease enzyme can identify particular base sequences and cleave, or cut these sequences at specific places. Nuclease enzymes are capable of cleaving the bond between two adjacent nucleotides located on the same strand of DNA. If a nuclease removes one or more nucleotides from the 5' end of a nucleic acid molecule, it is said to have “5' to 3' activity”; nucleases having 5' to 3' activity are called 5' nucleases. Conversely, if a nuclease removes a nucleotide from the 3' end of a nucleic acid molecule, it is said to have “3' to 5' activity.” A nuclease that can remove a nucleotide from the end of a nucleic acid strand is said to have “exonuclease” activity, whereas a nuclease that can remove a nucleotide from the middle of a nucleic acid strand has “endonuclease” activity. Structure-specific enzymes can identify specific nucleic acid structures and cleave those structures at specific sites. Some polymerases, such as the E. coli DNA Pol I and the Tag polymerase, are able to both synthesize and cleave DNA. Enzymes with both capabilities are said to have both “polymerase” activity and “nuclease” activity.

C. The Patents

1. Background technology

Both plaintiffs ’543 and ’314 patents claim methods for detecting the presence of a target nucleic acid molecule by forming nucleic acid cleavage structures and cleaving them in a site-specific manner so as to release distinct detectable non-target cleavage products. When two oligonucleo-tides are mixed under certain reaction conditions with a target nucleic acid having a particular base sequence, the two oli-gonucleotides will hybridize to the target in a specific manner, creating a cleavage structure. (The cleavage structure claimed in the ’543 patent differs from that claimed in the ’314 patent.) When these cleavage structures are cleaved by a cleaving means that is mixed with the target and two oligonucleotides, they release the detectable non-target cleavage products. The detection of these non-target cleavage products signifies the existence of the particular base sequence in the target strand. Identifying specific target sequences can be used in forensics or to identify and study genetically-based diseases and viral or bacterial infections.

2. The ’5k3 patent

Claim 16 is the only claim in the ’543 patent implicated in this case. It reads as follows:

16. A method of detecting the presence of a target nucleic acid molecule by detecting non-target cleavage products comprising:

a)providing:

I) a cleavage means,

ii) a source of target nucleic acid, said target nucleic acid having a first region, a second region and a third region, wherein said first region is downstream from said second region and wherein said second region is contiguous to and downstream from said third region;

iii) first and second oligonucleotides having 3' and 5' portions, wherein said 3' portion of said first oligonu-cleotide contains a sequence complementary to said third region of said target nucleic acid and wherein said 5' portion of said first oligonucleotide and said 3' portion of said second oligonucleotide each contain sequence fully complementary to said second region of said target nucleic acid, and wherein said 5' portion of said second oligonucleotide contains sequence complementary to said first region of said target nucleic acid;

b) mixing, in any order, said cleavage means, said target nucleic acid, said first oligonucleotide and said second oligonu-cleotide to create a reaction mixture under reaction conditions such that at least said 3' portion of said first oligonucleo-tide is annealed to said target nucleic acid and wherein at least said 5' portion of said second oligonucleotide is annealed to said target nucleic acid so as to create a cleavage structure and wherein cleavage of said cleavage structure occurs to generate non-target cleavage products, each non-target cleavage product having a 3'-hydroxyl group; and

c) detecting said non-target cleavage products.

The following is a schematic depiction of the cleavage structure described in claim 16:

Illustration No. 1

The section of the target nucleic acid labeled “Y” depicts the “first region,” the section labeled “X” depicts the “second region” and the segment labeled “Z” depicts the “third region.” The oligonucleo-tide labeled “probe” represents the “first oligonucleotide” and the other labeled “invader” represents the “second oligonucleo-tide.”

Describing claim 16 in terms of this depiction, the S' portion of the invader must contain a sequence complementary to region Y; both the 3' portion of the invader and the 5' portion of the probe must contain a sequence fully complementary to region X; and the 3' portion of the probe must contain a sequence complementary to region Z. Regions X and Z must be contiguous. The cleavage structure is created when the 3' portion of the probe anneals to region Z, the S' portion of the invader anneals to region Y and the 5' end of the probe and the 3' end of the invader overlap in region X.

Once the cleavage structure is formed, it can be cleaved by the cleavage means. The cleavage process generates non-target cleavage products. Specifically, the non-target cleavage product of claim 16 is derived from the S' end of the first oligonu-cleotide (the probe) when it is cleaved in the cleavage structure; it is not derived from the target nucleic acids. The cleavage fragments from the 5' end of the first oligonucleotide have a 3' hydroxyl group.

3. The ’81k patent 3.

Claim 1 of the ’314 patent reads as follows:

I. A method for detecting the presence of a target nucleic acid molecule by detecting non-target cleavage products comprising:

a) providing:

I) a cleavage agent;

ii) a source of target nucleic acid, said target nucleic acid comprising a first region and a second region, said second region downstream of and contiguous to said first region;

iii) a first oligonucleotide, wherein at least a portion of said first oligonu-cleotide is completely complementary to said first portion of said first target nucleic acid;

iv) a second oligonucleotide comprising a 3' portion and a 5' portion, wherein said S' portion is completely complementary to said second portion of said target nucleic acid;

b) mixing said cleavage agent, said target nucleic acid, said first oligonucleo-tide and said second oligonucleotide to create a reaction mixture under reaction conditions such that at least said portion of said first oligonucleotide is annealed to said first region of said target nucleic acid and wherein at least said 5' portion of said second oligonucleotide is annealed to said second region of said target nucleic acid so as to create a cleavage structure, and wherein cleavage of said cleavage structure occurs to generate non-target cleavage product; and c) detecting the cleavage of said cleavage structure.

Claim 1 contains no requirement that the 3' portion of the second oligonucleotide be complementary to the target nucleic acid. It does require that the non-target cleavage products be derived from the first oligonucleotide in the cleavage structure and not from the target nucleic acid.

Claims 5 and 7 depend on claim 1. They read as follows:

5. The method of claim 1, wherein said detecting the cleavage of said cleavage structure comprises detection of fluorescence.

7. The method of claim 1, wherein said detecting the cleavage of said cleavage structure comprises detection of fluorescence energy transfer.

Claims 12 and 14 are dependent on claim 11, which claims “[t]he method of claim 1, wherein said cleavage agent comprises a structure-specific nuclease.” Claims 12 and 14 read as follows:

12. The method of claim 11, wherein said structure-specific nuclease comprises a thermostable structure-specific nuclease.

14. The method of claim 13, wherein said 5'-nuclease comprises a thermosta-ble 5'-nuclease.

4. Terminology

As used in these claims, the term “contiguous” means that there are no nucleotides between the relevant sections or regions; “annealed” means the pairing of complementary nucleic acid molecules via hydrogen bonding to form a duplex, or double stranded base pair or base-paired region of nucleic acid; “complementary” refers to bases that are related by base pairing rules; and “completely complementary” means that each and every nucleotide of a completely complementary portion can base pair to each and every corresponding nucleotide of the target sequence. The common and ordinary meaning of the term “providing” is “to furnish, supply or to make available.” Neither patent requires that the reagents be provided in any particular manner. Providing can take place either before or during the mixing step; however, all reagents must be provided before mixing is complete.

In both patents, the term “oligonucleo-tide” is defined in the claim specifications as “a molecule comprised of two or more deoxyribonucleotides or ribonucleotides, preferably at least 5 nucleotides, more preferably at least about 10-15 nucleotides and more preferably at least about 15 to 30 nucleotides. The exact size will depend on many factors, which in turn depends on the ultimate function or use of the oligonu-cleotide.” ’543 Pat., col.18, Ins. 58-6; ’314 Pat., col. 16, Ins. 10-14. Further, the specifications state that “the oligonucleotide may be generated in any manner, including chemical synthesis, DNA replication, reverse transcription, or a combination thereof.” ’543 Pat., col.18, Ins. 64-67; ’314 Pat., col. 16, Ins. 16-19. One of ordinary skill in the art would understand that these techniques require unique reaction conditions.

The term “primer” means “an oligonu-cleotide [ ] capable of acting as a point of initiation of synthesis when placed under conditions in which primer extension is initiated.” ’543 Pat., col. 19, Ins. 21-25; ’314 Pat., col. 16, Ins. 39-43. The specifications make clear that a primer may occur naturally or may be produced synthetically. ’543 Pat., col. 19, Ins. 25-26; ’314 Pat., col. 16, Ins. 43-44. A “probe oligonucleotide” is defined as “an oligonu-cleotide which interacts with a target nucleic acid to form a cleavage structure in the presence or absence of an invader oligonucleotide.” ’543 Pat., col. 21, Ins. 27-30; ’314 Pat., col. 18, Ins. 47-50. “When annealed to the target nucleic acid, the probe oligonucleotide and target form a cleavage structure and cleavage occurs within the probe oligonucleotide.” ’543 Pat., col. 21, Ins. 30-32; ’314 Pat., col. 18, Ins. 50-52.

As defined in the specifications, the term “cleavage means” “refers to any means which is capable of cleaving a cleavage structure, including but not limited to enzymes.” ’543 Pat., col. 20, Ins. 55-57; ’314 Pat., col. 18, Ins. 6-8. Further, the specifications state that “[t]he cleavage means of the invention cleave a nucleic acid molecule in response to the formation of cleavage structures; it is not necessary that the cleavage means cleave the cleavage structure at any particular location within the cleavage structure.” ’543 Pat., col. 21, Ins. 2-7; ’314 Pat., col. 18, Ins. 20-25. These definitions make it clear that “cleavage means” may include “native DNAPs having 5' nuclease activity (e.g., Taq DNA polymerase, E. coli DNA polymerase I) and, more specifically, modified DNAPs having 5' nuclease but lacking synthetic activity.” ’543 Pat., col. 20, Ins. 58-61; ’314 Pat., col. 18, Ins. 9-12.

The specifications identify certain types of enzymes that may act as a “cleavage means.” Portions of the specifications state that “[i]n one embodiment, the means for cleaving is a cleaving enzyme comprising 5' nucleases derived from thermostable DNA polymerases.” ’543 Pat., col. 5-6, Ins. 67-2; ’314 Pat., col. 8, Ins. 24-27. Later, the specifications provide that

The 5' nucleases of the invention are capable of cleaving this structure but are not capable of polymerizing the extension of the 3' end of the first oligonu-cleotide. The lack of polymerization activity is advantageous as extension of the first oligonucleotide results in displacement of the annealed region of the second oligonucleotide and results in moving the site of cleavage along the second oligonucleotide. If polymerization is allowed to occur to any significant amount, multiple lengths of cleavage product will be generated. A single cleavage product of uniform length is desirable as this cleavage product initiates the detection reaction.

’543 Pat., col. 29, Ins. 15-26; ’314 Pat., col. 26, Ins. 10-21.

The specifications make clear that the cleavage means is not restricted to enzymes having solely 5' nuclease activity. ’543 Pat., col. 21, Ins. 8-9; ’314 Pat., col. 18, Ins. 26-27. “The cleavage means may include nuclease activity provided from a variety of sources including the Cleavase.RTM. enzymes, the FEN-1 en-donucleases (including RAD2 and XPG proteins), Taq DNA polymerase and E. coli DNA polymerase I.” ’543 Pat., col. 21, Ins. 9-13; ’314 Pat., col. 18, Ins. 27-31. Another portion of the specifications provides that in a different embodiment, “the cleavage means is a structure-specific nuclease; particularly preferred structure-specific nucleases are thermostable structure-specific nucleases.” ’543 Pat. col. 8, Ins. 23-26; ’314 Pat., 8, Ins. 24-27. “Structure-specific nucleases” are defined as “enzymes which recognize specific secondary structures in a nucleic molecule and cleave these structures.” ’543 Pat., col. 20-21, Ins. 66-2; ’314 Pat., col. 18, Ins. 17-20.

Both specifications specify that the term “hybridization” “is used to refer to the pairing of complementary nucleic acids.” ’543 Pat., col. 17, Ins. 53-54; ’314 Pat., col. 15, Ins. 3-4. In addition, they state that “ ‘[h]ybridization’ methods involve the annealing of a complementary sequence to the target nucleic acid.” ’543 Pat., col. 19., Ins. 41-42; ’314 Pat., col. 16, Ins. 60-61.

The “target nucleic acids” may be obtained using standard molecular biological techniques, including isolation from a tissue sample, tissue culture cells or samples containing bacteria and or viruses. ’543 Pat., col. 38, Ins. 10-14; ’314 Pat., col. 35, Ins. 5-10. They “may also be transcribed in vitro from a DNA template or may be chemically synthesized or generated in a PCR [polymerase chain reaction].” ’543 Pat., col. 38, Ins. 14-16; ’314 Pat., col. 35, Ins. 10-12.

One of ordinary skill in the art would understand that the “mixing” would occur under specific, appropriate reaction conditions to allow the claimed reagents to form a cleavage structure. One of ordinary skill in the area would also understand that the conditions would depend on the particular embodiment of the claimed method. If a polymerase chain reaction is used to generate an oligonucleotide or a target nucleic acid, one of ordinary skill in the art would know that the reaction conditions would include a change in temperature.

5. Third Wave Technologies, Inc. v. Era-Gen Biosciences, Inc., 02-C-507-C

In Third Wave Technologies, Inc. v. EraGen Biosciences, Inc., 02-C-507-C, I construed certain terms found in claim 16 of the ’543 patent and claim 14 of the ’314 patent. In an order entered March 18, 2003, I held that in both claims, reagents may be provided in any manner before or during the mixing step. In other words, if the cleavage means, target nucleic acid and first and second oligonucleotides are provided before mixing is complete, then the requirements for the providing step have been satisfied. I noted that “there is no language in the claim requiring any of the ingredients to be fully formed when they are added to the mix” and that “the patents do not differentiate between methods of creating oligonucleotides inside or outside the mix, before or during the mixing step.”

In addition, I defined the term “complementary” as referring to “bases that are related by the base pairing rules” that are not limited to bases that hydrogen bond in a standard “Watson-Crick fashion” and that “completely complementary” means that “every base in a nucleotide sequence is ‘complementary.’ ” Finally, I concluded that the term “non-target cleavage products” means products of a cleavage reaction that are derived from the 5' portion of the first oligonucleotide.

6. Prior art

a. Gelfand art

The prior art for both the ’543 and ’314 patents includes U.S. Patent No. 5,210,015 (the ’015 patent) and U.S. Patent No. 5,487,972 (the ’972 patent) (collectively, “the Gelfand art”). In the Gelfand art, a polymerase enzyme was used to extend a primer in the presence of a probe that was base-paired to the template in front of (downstream of) the extended primer. This polymerase extension resulted in cleavage of the probe and detection of cleavage products. The enzyme used throughout the examples in the Gelfand art is Tag polymerase. The United States Patent and Trademark Office determined that the Gelfand art anticipated claim 26 in plaintiffs application for U.S. Patent No. 5,846,717. (Both the ’543 patent and the ’314 patents claim priority from the ’717 patent and specifically, claims 1 and 19 of the ’717 patent claim the same structure as claim 16 in the ’543 patent except that claims 1 and 19 require that “the combined melting temperature of said complementary regions within said 5' and 3' portions of said first oligonucleotide when annealed to said target nucleic acid is greater that the melting temperature of said 3' portion of said first oligonucleo-tide”)

In response, plaintiff explained that its claim specifies a cleavage structure where the two oligonucleotides overlap in their hybridization to the target whereas the Gelfand patent specifies that the two oligo-nucleotides be “adjacent” to one another, meaning that the two oligonucleotides may be located anywhere from zero to twenty nucleotides apart. Thus, plaintiff argued, “adjacent” does not encompass overlapping oligonucleotides. The examiner subsequently withdrew the rejection. During plaintiffs prosecution of the ’543 patent, plaintiff emphasized again that in the Gelfand art, there is no overlap in the regions of complementarity of the two oli-gonucleotides.

b. Lyamichev and Dahlberg

The United States Patent and Trademark Office rejected as obvious several of the claims in plaintiffs application for the ’543 patent, including claim 16 in view of Lyamichev et al. (Science 260:778-783 (May 1993)) and Dahlberg et al. U.S. Patent No. 5,422,253. In plaintiffs response, it depicted the cleavage structures in Lyamichev and the ’253 patent as having the following structures:

Illustration No. 2

Plaintiff pointed out that in contrast to what its own patents claim, region 2 and region 3 are not contiguous in the structure disclosed in Lyamichev and the ’253 patent; the two regions are separated by nucleotides.' In addition, plaintiff added language to claim 16 specifying the need for contiguity between regions 2 and 3.

The patent examiner responded that “the amendment of the claims to recite that the regions are contiguous does not overcome the prior art for the following reasons. Webster’s II dictionary defines contiguous as 1) sharing a boundary or edge or 2) nearby; adjacent. Therefore, the regions of the target nucleic acid of the prior art meet the definition of being contiguous as is now claimed.” However, the examiner added, “the prior art does not teach or suggest or provide sufficient motivation and guidance to obtain the instantly claimed invention wherein the oligonucleo-tides each contain a region fully complementary to the target .... ” Plaintiff amended its application to specify that the 5' portion of the first oligonucleotide and the 3' portion of the second oligonucleotide “each contain a sequence fully complementary to said second region” of the target nucleic acid. The examiner emphasized this amended language in allowing the claim.

c. The ’311 and ’402 patents

The prior art for the ’543 patent includes U.S. Patent No. 5,541,311 (the ’311 patent) and U.S. Patent No. 5,614,402 (the ’402 patent). The Patent and Trademark Office rejected claims 16-18 of the ’543 patent as obvious in view of the ’311 patent and the ’402 patent. Although the examiner mistakenly believed that the ’311 patent and the ’402 patent did not teach the generation of non-target cleavage products having a free hydroxyl (-OH) group at the 3' terminus, she contended nevertheless that it would have been obvious to use the cleavage structures in a method to obtain non-target cleavage products. In its response, plaintiff argued that neither the ’311 patent nor the ’402 patent disclosed a 5' portion of the downstream oli-gonucleotide that is complementary to a second region of the target.

d. Lundquist

Included in the list of approximately 168 references listed in plaintiffs application for the ’314 patent was the publication Lundquist et al., Transient generation of displaced single-stranded DNA during nick translation, 31 CELL 1982, at 53-60. The article discloses a method for detecting cleavage of the following cleavage structure by E. coli DNA polymerase I:

Illustration No. 3

In its information disclosure statement, plaintiff distinguished the references it had listed, noting that “[u]nlike the presently claimed invention, these references do not disclose methods for detecting target nucleic acids based on the cleavage of invasive cleavage structures (e.g. using cycling reactions).” The ’314 patent specification provides that “[a]n invasive cleavage structure supports cleavage of the probe in a region that, in the absence of an upstream oligonucleotide, would be expected to be basepaired to the • target nucleic acid.” ’314 Pat., col. 40, Ins. 12-15. Plaintiff did not cite the Lundquist article in its application for the ’543 patent.

D. The FullVelocity™ Products

Defendant’s two FullVelocity™ products at issue, the QPCR Master Mix and the QRT-PCR Master Mix, are designed for the probe-based detection of target nucleic acid molecules. Both are designed to detect the presence of a target nucleic acid and have been used for that purpose. Defendant has offered for sale and sold these products with corresponding instruction manuals to parties in the United States starting in 2004. In 2004, it sold 244 units for over $110,000. It has made product information and instruction manuals available on the internet since at least April 8, 2004. Defendant intends that its customers use the FullVelocity™ products in the manner set forth in the instruction manuals; defendant has stipulated that the products have no other substantial use; and it informs its customers in its manuals that the products “may not be used in any manner other than as provided herein.” At least two of its customers have used the FullVelocity™ products to detect the presence of target nucleic acids. The QRT-PCR Master Mix involves the same process for detecting target nucleic acid as is used in the QPCR Master Mix plus an additional step of converting RNA into complementary DNA (cDNA).

1. Reagents included with FullVelocity™ products

Defendant’s products contain reagents used for polymerase chain reaction amplification and probe-based detection of a target nucleic acid. Both mixes include a buffer, a reference dye and an enzyme formulation comprising two enzymes: a DNA polymerase and a flap endonuclease. This enzyme formulation possesses cleavage activity and can cleave a probe.

The DNA polymerase included in defendant’s product is V93R Pfu Exo-DNA, which is a mutation of a naturally occurring Pfu DNA polymerase, or a “wild type” Pfu polymerase, that does not exhibit nuclease activity. During a polymerase chain reaction involving defendant’s Full-Velocity™ products, this mutant Pfu polymerase extends a primer along a target strand by adding bases complementary to the target to the 3' end of the primer. While it is extending the primer, the mutant Pfu polymerase is bound to both the target nucleic acid and to the 3' end of the primer. The front end of a Pfu polymerase arrives at a nucleotide on the complementary strand before the portion of the polymerase that adds nucleotides. One study has suggested that the front end of a Pfu polymerase is approximately 4-6 nucleotides ahead of the last nucleotide added to the 3' end of the primer. When the mutant Pfu polymerase encounters a downstream hybridized oligonucleotide, it will extend the primer so that the 3' end of the extended primer displaces the downstream oligonucleotide. The displaced portion creates an overlapping flap. A Pfu, polymerase weighs approximately 90,000 Daltons, a unit of measurement corresponding to roughly the weight of a single hydrogen atom.

The flap endonuclease supplied in the FullVelocity™ enzyme formulation is Pfu FEN-1. Pfu FEN-1 is a thermostable and structure-specific nuclease having 5' nuclease activity. Pfu FEN-1 is a ther-mostable 5' nuclease enzyme capable of cleaving the cleavage structure claimed in claim 16 of the ’543 patent and in claim 1 of the ’314 patent. In one peer-reviewed study of Pfu FEN-1, no cleavage was detected when an invader oligonucleotide was missing or when there was no overlap between two oligonucleotides. The study concluded that “the Pfu FEN1 en-donuclease requires at least one overlapping nucleotide between the signal and invasive probes to recognize and cleave the displaced 5' end of the signal probe.” Victor Lyamichev et al., Polymorphism Identification and Quantitative Detection of Genomic DNA by Invasive Cleavage of Oligonucleotide Probes, 17 NATURE BIOLOGY Mar. 1999, at 292. The invader oligonucleotide used to test cleavage with two non-overlapping oligonucleotides has a G base on its 3' terminal while the 3' terminal nucleotides on the invader oli-gonucleotides used to test cleavage of an overlapping oligonucleotide structures contained an A base. However, the article does not discuss what if any ramifications the particular base found in the 3' terminal nucleotide might have had on the outcome of the experiments. The study showed also that when a Pfu FEN-1 en-donuclease cleaves an overlapping oligo-nucleotide structure, the cleavage takes place on the 3' side of the last nucleotide of the upstream oligonucleotide. The Pfu FEN-1 enzyme provided in defendant’s products has not been altered or mutated.

2. Instructions for FullVelocity™ product use

a. Additional materials required

Defendant instructs its users to supply certain materials for use with its FullVel-ocity™ products. Those materials include a probe (first oligonucleotide), a primer (second oligonucleotide) and a template including a target nucleic acid. The FullVel-ocity™ mixes cannot be used to detect a target nucleic acid sequence without a probe, a primer and a source of target nucleic acid. The probe anneals to the target nucleic acid to form part of the structure that is cleaved. Both mixes use probes as reporters and are designed to be used with hydrolysis probes specifically. Hydrolysis probes are oligonucleotides with a DNA backbone that carry one or more labels. Each hydrolysis probe has a fluorophore that is usually located at its 5' end and a quencher that is either internal or on its 3' end. The positions of the fluorophore and the quencher can be reversed. Regardless of their respective positions and regardless whether the probe is annealed to the target or free floating, no fluorescence will be observed from the fluorophore so long as the hydrolosis probe remains intact. The 5' end of the probe contains a 3' hydroxyl group. When hydrolysis probes that have hybridized to a target nucleic acid are cleaved, they can generate a detectable signal.

A portion of the primer near its 5' end must contain a sequence of nucleotides that is complementary to the target strand and anneals to it. The primer is extended by the Pfu polymerase to a point where at least its 3' end is completely complementary to a sequence in the target nucleic acid and a sequence in the probe. (Defendant attempts to put this fact into dispute, arguing that “[t]here is no evidence that the terminal nucleotide on the 3' end of the extended primer is complementary to a sequence on the target nucleic acid that is also complementary to a sequence in the probe because the complex, which is of substantial size, may displace the probe many nucleotides in advance of the addition of nucleotides to the 3' end of the extended primer by the polymerase.” Deft.’s Resp. to Pit’s PFOF, dkt. # 50, at 78-79, ¶ 332. The first and most obvious problem with this argument is that defendant has ignored the evidence in the record supporting plaintiffs position, namely the expert testimony plaintiff cited in support of its proposed finding of fact. Second, defendant does not cite any evidence suggesting that the displacement process not only moves part of the probe away from the target but also reorders its nucleotide sequence. So long as displacement does not alter base sequences, the probe and target remain “complementary” even though physically moved apart.) A cleavage structure is formed when portions of the probe and the extended primer are annealed to the target nucleic acid.

In addition, defendant’s product manuals instruct users to provide experimental gDNA, cDNA, plasmid DNA or RNA and to amplify whichever one of these substances is selected with a polymerase chain reaction. In the event that a user is employing RNA, defendant instructs the user to synthesize a DNA copy of the RNA using reverse transcriptase, which is supplied in the FullVelocity™ QRT-PCR Master Mix kit. This DNA copy, or cDNA, can be used as a template for amplification during PCR.

b. Methodology for using FullVelocity™ mixes

The following figure appears in the instruction manuals for the both QPCR and QRT-PCR:

Illustration No. 4

The manuals for both mixes instruct the user to combine water, the QPCR FullVel-oeity™ enzyme solution, experimental probes, upstream primers, downstream primers and the reference dye in that order. (In addition, the QRT-PCR mix instructions calls for the addition of StrataS-cript RT/RNase block enzyme mixture and the FullVelocity enzyme.) The manuals next call for the gentle mixing of these reagents and distribution to PCR reaction tubes. At that point, the user is to add a specified amount of experimental gDNA, cDNA, plasmid DNA or RNA and then gently mix the reaction again. When first added to the mixture, the DNA or RNA is double stranded. Neither the probes nor the primers can hybridize to the DNA or RNA while it remains double stranded. The mixture is then centrifuged briefly before being placed in a thermocycler where it is subject to a series of designated temperature cycles.

The manual for the QPCR Master Mix calls for the mixture to be subject to two minutes at 95 C and then 40 cycles of 10 seconds at 95 C followed by 30 seconds at 60 C. The instructions for the QRT-PCR Master Mix calls for the mixture to be subject to 50 C for 30 minutes, followed by 2 minutes at 95 C and finally, 40 cycles of 10 seconds at 95 C, followed by 30 seconds at 60 C. At 95 C, the double stranded DNA or RNA will undergo denaturation, permitting the oligonucleotides to hybridize to the newly separated single strands. These reaction conditions allow the probe and the extended primer to anneal to the target to form a structure that is cleavable by the Pfu FEN-1 endonuclease. The hydrolysis probe anneals to the nucleic acid strand downstream of the primer. The Pfu polymerase extends the 3' end of the primer until it encounters the 5' end of the annealed probe. When the 3' end of the primer encounters the 5' end of the probe, the 5' end of the probe is partially displaced. The displaced 5' end has a sequence that is completely complementary to the portion of the target strand that is completely complementary to the displacing portion of the 3' end of the extended primer.

The reaction conditions permit Pfu FEN-1 to cleave the displaced 5' end of the probe. In order to do so, the Pfu FEN-1 enzyme must bind to the 3' end of the extended primer. The Pfu FEN-1 cannot bind to the 3' end of an extended primer at the same time that the mutant Pfu polymerase is bound to the 3' end of the primer. When the reagents are subjected to the reaction conditions, the mutant Pfu polymerase dissociates from the extended primer and the probe. Once the mutant Pfu polymerase dissociates, Pfu FEN-1 binds to the 3' end of the extended primer and cleaves the cleavage structure. When the probe is cleaved, the 5' end that generally contains a fluorophore is separated from the quencher, which is typically on the 3' end or internal. When the flou-rophore is disconnected from the quencher, it will release a detectable signal in the form of fluorescence.

In 2004, one of defendant’s staff scientists gave a Power Point presentation explaining defendant’s QPCR reagent technology. The presentation contained the following depiction under the title “Full-Velocity™ Probe Based Chemistry”:

Illustration No. 5

c. Defendant’s experiment

Defendant conducted an experiment with the purported goal of determining whether the FullVelocity™ products and process result in the claimed cleavage structures. Although the instruction manuals for both mixes and defendant’s senior staff scientist say that the FullVelocity™ products are to be used with complementary probes that anneal to the target nucleic acid, defendant performed its experiment using probes with 29 non-complementary bases on their 5' ends. (Defendant has informed plaintiff of its intention to change its instructions to guide customers to design probes that could generate a flap that is not complementary to the target nucleic acid.) Defendant mixed these probes with target nucleic acid and primers. In one experiment, defendant introduced a Taq polymerase to this mixture; in another, it introduced a Pfu polymerase; and in a third, it added both a Pfu polymerase and a FEN-1 nuclease. The Taq mixture generated cleavage products 29-30 nucleotides in length, the Pfu mixture did not generate any detectable cleavage products, and the Pfu and FEN-1 combination generated cleavage products 29-30 nucleotides in length. As noted above, unlike the Pfu polymerase, Taq polymerase exhibits 5' to 3' nuclease activity.

After conducting the experiments, defendant’s expert drew several conclusions from these results. He noted that the Pfu polymerase alone could not cleave the probe. With respect to the Taq polymerase mixture, he concluded that “Taq can cleave a non-complementary flap structure without the need to significantly displace the complementary, annealed portion of the probe molecule.” As for the Pfu polymerase and FEN-1 combination, defendant’s expert asserts that “[g]iven the nearly identical cleavage product sizes generated by FullVelocity™ and the Taq polymerase ... the number of bases the Taq polymerase displaces before it cleaves a probe segment is similar, if not the same, as the number of bases displaced by the complex formed by the Pfu mutant polymerase and FEN-1, used by [defendant].” Plaintiffs expert reviewed the experiment protocol and results and concluded that it shows that the claimed cleavage structures are formed when the FullVelocity™ products are used as directed because Pfu FEN-1 is very specific and will efficiently cleave only particular structures. Although Pfu FEN-1 will cleave non-preferred structures, plaintiffs expert asserts that the cleavage of non-preferred structures occurs so slowly that the short temperature cycling directed in the Full-Velocity™ manuals will not allow for a detectable level of cleavage.

OPINION

Infringement analysis is a two-step process. First, courts construe the claims at issue and then they compare the properly construed claims to the accused device. Cybor Corp. v. FAS Technologies, Inc., 138 F.3d 1448, 1454 (Fed.Cir.1998) (en banc); Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.Cir.1996); Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed.Cir.1995) (en banc), aff'd, 517 U.S. 370, 116 S.Ct. 1384, 134 L.Ed.2d 577 (1996). A device infringes a patent claim if it contains every limitation set forth in that claim, either literally or by equivalence. Johnson Worldwide Assocs. v. Zebco Corp., 175 F.3d 985, 988 (Fed.Cir.1999). “A patent is infringed if any claim is infringed.” Pall Corp. v. Micron Separations, Inc., 66 F.3d 1211, 1220 (Fed.Cir.1995). Claim construction is a legal determination to be made by the court while infringement is a question of fact. Vitronics, 90 F.3d at 1582; Insituform Techs., Inc. v. Cat Contracting, Inc., 161 F.3d 688, 692 (Fed.Cir.1998).

This opinion is limited to the issue of infringement. Defendant has proposed extensive facts regarding the prosecution history of both the ’543 patent and the ’314 patent that might have been made in conjunction with either a defense of patent invalidity for obviousness or of fraudulent procurement. However, defendant does not argue invalidity or fraudulent procurement, but instead uses the prosecution history in its arguments related to claim construction. “It is beyond cavil that a district court does not have authority to invalidate a patent at its own initiative if validity is not challenged by a party.” Lannom Manufacturing Co., Inc. v. U.S. Intern. Trade Commission, 799 F.2d 1572, 1579 (Fed.Cir.1986); see also 35 U.S.C. § 282 (once patents are issued by United States Patent and Trademark Office, they are presumed to be valid; burden of establishing invalidity rests on party asserting it); Seiko Epson Corp. v. Nu-Kote International, Inc., 190 F.3d 1360, 1367 (Fed.Cir.1999) (“A ruling of inequitable conduct in the PTO must be supported by clear and convincing evidence of material misrepresentation, made with the intent to deceive or mislead the patent examiner.”).

Although defendant did not develop an invalidity argument on summary judgment, it appears that it intends to pursue this theory in the future. In a rebuttal expert report, defendant’s expert Joseph O. Falkinham III offers the opinion that the patents are invalid in light of prior art. Plaintiff has moved to strike these portions of the expert report. Because the issue of invalidity is not relevant to the motion at hand, I will leave the motion to strike for the magistrate judge to resolve before trial.

A. Rules Governing Infringement Analysis

1. Claim construction

“[I]n interpreting an asserted claim, [a] court should look first to the intrinsic evidence of record, i.e., the patent itself, including the claims, the specification and, if in evidence, the prosecution history.” Vitronics, 90 F.3d at 1582. Construction of the disputed terms begins with the claim language, which serves to delineate the virtual metes and bounds of the invention, letting competitors know what they can and cannot do in the way of making and selling similar products. Bell Communications Research, Inc. v. Vitalink Communications Corp., 55 F.3d 615, 619 (Fed.Cir.1995) (citing Yale Lock Manufacturing Co. v. Greenleaf 117 U.S. 554, 559, 6 S.Ct. 846, 29 L.Ed. 952 (1886)). Thus, claim construction must adhere carefully to the precise language of the claims that the patent officer has allowed. Autogiro Co. of America v. United States, 181 Ct.Cl. 55, 384 F.2d 391, 396 (1967) (“Courts can neither broaden nor narrow the claims to give the patentee something different than what he set forth [in the claim].”).

In construing the language of the claims, “[t]here is a ‘heavy presumption’ that the terms used in claims ‘mean what they say and have the ordinary meaning that would be attributed to those words by persons skilled in the relevant art.’ ” SuperGuide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 874-75 (Fed.Cir.2004) (quoting Texas Digital Systems, Inc. v. Telegenix, Inc., 308 F.3d 1193, 1202 (Fed.Cir.2002)). Dictionaries, encyclopedias and treatises may be used in determining the ordinary and customary meaning of claim term language, so long as the definition does not contradict any definition found in the patent documents or ascertained from them. Phillips v. AWH Corp., 415 F.3d 1303 (Fed.Cir.2005). “[U]nless compelled to do otherwise, a court will give a claim term the full range of its ordinary meaning.” Rexnord Corp. v. Laitram Corp., 274 F.3d 1336, 1342 (Fed.Cir.2001).

“If the disputed claim term ‘is a term with no previous meaning to those of ordinary skill in the prior art, its meaning, then, must be found elsewhere in the patent.’ ” Novartis Phamaceuticals Corp. v. Abbott Laboratories, 375 F.3d 1328, 1334 (Fed.Cir.2004) (quoting J.T. Eaton & Co. v. Atlantic Paste & Glue Co., 106 F.3d 1563, 1568 (Fed.Cir.1997)). In most instances, the specification “is the single best guide to the meaning of a disputed term.” Vitronics, 90 F.3d at 1582. Although the patent specification may not be used to rewrite the claim language, SuperGuide, 358 F.3d at 875, the specification may be used to interpret what the patent holder meant by a word or phrase in the claim, E.I. du Pont de Nemours & Co. v. Phillips Petroleum Co., 849 F.2d 1430, 1433 (Fed.Cir.1988).

After considering the claim language and the specification, a court may consider the final piece of intrinsic evidence: the patent’s prosecution history. Vitronics, 90 F.3d at 1582. “[Statements made during the prosecution of a patent may affect the scope of the invention.” Rexnord, 274 F.3d at 1343. This is especially true if a particular interpretation of the claim was considered and specifically disclaimed during the prosecution of the patent. Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 30, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997); Vitronics, 90 F.3d at 1582-83. Generally, analysis of the intrinsic evidence will eliminate any ambiguity in the claim terms, rendering unnecessary any reference to extrinsic evidence. Vitronics, 90 F.3d at 1583.

2. Infringement

Infringement analysis requires a comparison of the properly construed claims with the allegedly infringing device or method to determine “whether all of the claim limitations are present, either literally or by a substantial equivalent, in the accused device.” Johnson Worldwide Associates, Inc. v. Zebco Corp., 175 F.3d 985, 988 (Fed.Cir.1999). “Literal infringement of a claim exists when each of the claim limitations ‘reads on,’ or in other words is found in, the accused device.” Allen Engineering Corp. v. Bartell Industries, Inc., 299 F.3d 1336, 1345 (Fed.Cir.2002). Under the doctrine of equivalents, “a product or process that does not literally infringe upon the express terms of a patent claim may nonetheless be found to infringe if there is ‘equivalence’ between the elements of the accused product or process and the claimed elements of the patented invention.” Warner-Jenkinson Co. v. Hilton Davis Chemical Co., 520 U.S. 17, 21, 117 S.Ct. 1040, 137 L.Ed.2d 146 (1997). Although infringement is a question of fact, IMS Technology, Inc. v. Haas Automation, Inc., 206 F.3d 1422, 1429 (Fed.Cir.2000), summary judgment is appropriate where there are no material facts in dispute. Johnson Worldwide, 175 F.3d at 988.

B. Infringement by the FullVelocity™ Products

1. Direct infringement, contributory infringement and active inducement

Before getting mired down in the intricacies of the claim requirements, I will address the parties’ dispute about defendant’s potential liability for any infringement of the method claims at issue that might have been performed with the Full-Velocity™ products. It is my understanding that plaintiff is pursuing its claims for direct infringement, contributory infringement and active inducement of infringement. See 35 U.S.C. § 271. Because “[l]iability for either active inducement of infringement or for contributory infringement is dependent upon the existence of direct infringement,” Joy Technologies, Inc. v. Flakt, Inc., 6 F.3d 770, 774 (Fed.Cir.1993) (citing cases), it is necessary to start by determining whether a jury could find defendant liable for direct infringement.

Direct infringement of a method or process claim occurs only when the process is performed and only by the entity performing the process. Id. at 774-75. “[A] method claim is not directly infringed by the sale of an apparatus even though it is capable of performing only the patented method.” Id. at 775. Although defendant concedes that it has used the FullVelocity™ products as directed, it contends that its use falls under either the experimental use exception or under the exemption in 35 U.S.C. § 271(e)(1), which applies solely for uses reasonably related to developing and submitting information used for federal regulations. Specifically, defendant asserts that it is testing the FullVelocity™ products in order to obtain approval from the Federal Food and Drug Administration.

Although defendant’s testing of its products might seem to fall under the experimental use exception, the Court of Appeals for the Federal Circuit has held that the scope of the exception is markedly narrow and that a defendant bears the burden of proving its applicability. Madey v. Duke University, 307 F.3d 1351, 1361 (Fed.Cir.2002). To qualify for the exception, a defendant’s actions must be performed “ ‘for amusement, to satisfy idle curiosity, or for strictly philosophical inquiry.’ ” Embrex, Inc. v. Service Engineering Corp., 216 F.3d 1343, 1349 (Fed.Cir.2000) (quoting Roche Products, Inc. v. Bolar Pharm. Co., 733 F.2d 858, 863 (Fed.Cir.1984)). Actions do not qualify for the experimental use defense when undertaken in the “ ‘guise of scientific inquiry’ ” if there are “ ‘definite, cognizable, and not insubstantial commercial purposes’ ” motivating them. Id. None of defendant’s evidence shows that its actions fall into the realm of idle curiosity. To the contrary, defendant’s assertion that it intends to obtain FDA approval in order to market its diagnostic assays belies any notion that its actions were without commercial motivation.

Defendant has similarly not supported its assertion that its actions are exempted under § 271(e)(1), which provides:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention ... solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

In a recently decided case, the United States Supreme Court held that § 271(e)(l)might apply to experimentation that is not ultimately the subject of an FDA submission. Merck KGaA v. Integra Lifesciences I, Ltd., — U.S. -, 125 S.Ct. 2372, 2382, 162 L.Ed.2d 160 (2005). (Although Merck was decided after briefing in this case was completed, both parties conscientiously alerted the court to its presence and explained what effect they thought it had to the present case.) However, the Court also confirmed that there are some bounds to the “reasonably related” standard. Id.

The exact scope of the “reasonably related” standard is not particularly relevant in this case in light of the fact that defendant has not actually said that its testing was related to obtaining FDA approval in any way. Instead, defendant relies on carefully crafted conjecture. In its proposed finding of fact, defendant asserts that it cannot market diagnostic assays without FDA approval. Dft’s Br., dkt. # 48, at 27. This assertion consists only of a bare legal conclusion that commercially marketed diagnostic assays require FDA approval; it explains nothing about defendant’s actions. Conspicuously missing from both defendant’s brief and its proposed findings of fact is a simple, straightforward assertion that its past testing of the FullVelocity™ products actually was performed in order to develop or submit information to the Food and Drug Administration.

Although defendant did not mention it in either its briefs or fact proposals, plaintiff acknowledges that defendant’s chief executive officer averred that defendant’s testing of its own products “is driven, in part by its desire to eventually expand the utility of its FullVelocity™ products and submit products using the FullVelocity™ platform for FDA approval.” Oparil Dec., dkt. # 51, Exh. 2, Sorge Dec. ¶ 29. However, in a deposition taken less than two months ago, this same individual conceded that defendant was only in the “start-up phase” of pursuing the diagnostics market for its FullVelocity™ products. Ahn Dec., dkt. # 56, Exh. 3, Sorge June 1, 2005 Dep. at 29:7-18.

In any event, I am not convinced that a remote desire to obtain FDA approval for products “using the FullVelocity™ platform” is sufficient to satisfy the “reasonably related” standard. Defendant’s construction of § 271(e)(1) would read the term “reasonably” out of the provision, granting immunity to any testing no matter how remotely related to a hypothetical submission to a federal agency. Moreover, § 271 provides exemption “solely for uses reasonably related to the development and submission of information” to federal regulatory agencies; defendant’s CEO testified that its testing was motivated “in part” by a desire to obtain FDA approval. Defendant will need evidence showing a far more concrete relationship between its past testing and its future intent to seek FDA approval if it intends to revive its argument under § 271(e)(1) at trial. At this point, its evidence is insufficient to support such an argument.

If plaintiff can prove direct infringement, it may be able to hold defendant liable for inducement pursuant to 35 U.S.C. § 271(b) or contributory infringement under 35 U.S.C. § 271(c). As for inducement liability, “a person infringes by actively and knowingly aiding and abetting another’s direct infringement.” Water Technologies Corp. v. Calco, Ltd., 850 F.2d 660, 668 (Fed.Cir.1988); see also 35 U.S.C. § 271(b). In its argument in opposition to a finding of inducement liability, defendant vacillates between asserting that the Full-Velocity™ products cannot be used in a way that infringes either the ’543 patent or the ’314 patent and that infringement will not occur when the FullVelocity™ products are used as directed. Because an entity cannot be held liable for infringement it did not actively promote, it is largely irrelevant whether the FullVelocity™ products can be used to infringe the claims. See, e.g., ICN Pharmaceuticals, Inc. v. Geneva Pharmaceuticals Technology Corp., 272 F.Supp.2d 1028, 1049 (C.D.Cal.2003) (potential off-label uses could not be basis for inducement liability where there was no evidence defendant encouraged or promoted off-label use). Furthermore, the parties have stipulated that “the materials for performing reactions with the accused FullVelocity™ products ... had no substantial use other than the use set forth in the instruction manuals and product inserts which accompany those products.” Oparil Dec., dkt. # 51, Ex. 55, ¶ 3. Thus, I will focus the analysis on whether the FullVelocity™ products cause infringement when used as directed. (Although defendant emphasizes its offer to change its instruction manuals so that its customers would be directed to use only probes with non comp