CPLRG™ 0037 - Enzo Biochem, Inc. v. Applera Corp. - Mar. 24, 2010

Enzo Biochem, Inc. v. Applera Corp., 599 F.3d 1325 (Fed. Cir. 2010) (LINN, Michel & Plager), rehearing and rehearing en banc denied, 605 F.3d 1347 (Fed. Cir. 2010) (PLAGER, dissenting from denial of panel rehearing) EnzoBiochem03242010

MAJOR ISSUES:  definiteness of claim language; biotechnology; nucelic acid labeling and detection; “substantially interfere”; summary judgment on invalidity by anticipation; prior art references; claim interpretation; claim differentiation

COMMENT.  Summary judgment is, potentially, an efficient tool for resolving disputes in which there is no dispute about the facts.  The costs of a trial are avoided.  Summary judgment can resolve complex issues of law but not facts.  However, separating law from fact is not so easy, especially with patent law issues such as indefiniteness, claim scope, and anticipation by prior art, and most especially when the underlying technology is complex, as this case illustrates.

1. LABEL AND DETECT NUCLEIC ACIDS.  Three patents concerned labeling and detecting nucleic acids (DNA and RNA).  U.S. Pat. No. 5,328,824 USPatNo5328824; U.S. Pat. No. No. 5,449,767 USPatNo5449767; U.S. Pat. No. 5,476,928 USPatNo5476928; U.S. Pat. No. 5,082,830 USPatNo5082830.

2. CLAIMS: “LINKAGE GROUP” ATTACH “A” TO “B”; DEFINED FUNCTIONALLY, NOT STRUCTURALLY; NOT INTERFERING SUBSTANTIALLY WITH HYBRIDIZATION AND DETECTION (OR, SIMPLY, DETECTION).  The patents claimed a compound defined by a structural formula and methods of using the compound as a detection probe.   The claimed compounds attached a nitrogenous base “B” to a chemical moiety “A” by a “linkage group.”  The claims defined “linkage” functionally, not structurally, to wit, as “not interfering substantially” with the ability of the probe to hybridize with a nucleic acid and to detect a signal (or, in the case of the ‘928 patent, substantially interfere with detection of the A moiety).

3. DISTRICT COURT: SUMMARY JUDGMENT OF INVALIDITY.  In an infringement suit, a district court granted an accused infringer’s motion for  summary judgment that the asserted claims of the three patents (‘824, ‘767, and ‘928) were invalid.
     a. INDEFINITENESS.  First, the district court held the claims were invalid for indefiniteness because the claims used an insufficiently defined phrase, “not interfering substantially” with hybridization and detection, in relation to a claim element (a linkage group).  The district court reasoned that the specification did not show how to gauge substantial interference or delimit a threshold at which interference prevents implementation of the method.
     b. ANTICIPATION BY AT LEAST THREE REFERENCES (KASAI, PINGOUD, BAUMAN)  Alternatively, the district court held that the claims were invalid for anticipation by at least three prior art references (Kasai, Pingoud, Bauman), which showed probes that, in fact, met the non-interference limitation.

4. DEFINITENESS; SUFFICIENT GUIDANCE ON WHEN A LINKAGE SUBSTANTIALLY INTERFERES WITH HYBRIDIZATION AND DETECTION.  The Federal Circuit held that the district court erred in finding indefiniteness.  The accused infringer argued that a DNA strand’s ability to hybridize varied with length and sequence and that a given linkage group might cause interference in some strands but not others.  However, the patent and its prosecution history provided sufficient guidance on when a compound would, as a linkage group, not substantially interfere with hybridization and detection.
     a. CLAIMS CANNOT BE BOTH INDEFINITE AND ANTICIPATED.  First, the district court erred in finding claims both anticipated and indefinite:  a claim cannot be anticipated unless it is construed and compared to a prior art reference; an indefinite claim is one that cannot be construed.
     b. “SUBSTANTIALLY”: MAGNITUDE, NOT APPROXIMATION.  “Substantially” can denote approximation or magnitude.  Deering Precision Instruments, LLC v. Vector Distrib. Sys., Inc., 347 F.3d 1314, 1323 (Fed. Cir. 2003).  Here, “substantially” pertained to the magnitude of interference.  See § 5233.
     c. DEPENDENT CLAIM SPECIFYING A PARTICULAR STRUCTURE PROVIDES SOME GUIDANCE ON INDEPENDENT CLAIM’S FUNCTIONAL ELEMENT.  The ‘824 and ‘767 patents contained a dependent claim specifying that the “linkage group” be a particular chemical structure ((-CH=CH–CH2–NH–).
           i. AT LEAST AS MUCH INTERFERENCE AS THE SPECIFIC STRUCTURE.  An ordinarily skilled person would presume that the dependent claim’s specific structure met the independent claim’s functional limitation and thus that that limitation (“not interfering substantially”) allowed at least as much interference as the specific structure.  AK Steel Corp. v. Sollac & Ugine, 344 F.3d 1234, 1242 (Fed. Cir. 2003).
            ii. IF DEPENDENT CLAIM STRUCTURE PRECLUDES HYBRIDIZATION, THE CLAIMS ARE INVALID, BUT FOR NON-ENABLEMENT, NOT INDEFINITENESS.  If a linkage group having the dependent claim’s specified structure entirely precluded hybridization, it would be invalid for lack of enablement, not indefiniteness.  Exxon Research & Eng’g Co. v. United States, 265 F.3d 1371, 1382 (Fed. Cir. 2001); Miles Labs., Inc. v. Shandon Inc., 997 F.2d 870, 875 (Fed. Cir. 1993).
     d. SPECIFICATION ADDITIONAL EXAMPLES; SOME CRITERIA.  The specification provided additional examples and “some criteria” for selecting suitable linkage groups.
          i. WELL KNOWN BONDS; “EVEN MORE PREFERRED”: FROM A PRIMARY AMINE AND CH2–NH STRUCTURE.  The specification stated that linkage groups could include well known bonds and that “[i]t is even more preferred that the chemical linkage group be derived from a primary amine, and have the structure –CH2–NH–, since such linkages are easily formed utilizing any of the well known amine modification reactions.”
          ii. WITHSTAND ALL NORMAL EXPERIMENTAL CONDITIONS.  The specification stated that the linkage must be such as to “withstand all experimental conditions to which normal nucleotides … are routinely subjected.”
          iii. GENERAL GUIDELINES FROM EXAMPLES; THERMAL DENATURATION PROFILES.  The specification taught that “thermal denaturation profiles” can be used to measure whether a linkage group interferes.  A strand’s hybridization bonding is indicated by its melting temperature so that a lower melting temperature is indicative of a weaker bond.  The specification gave two examples of satisfactory DNA strands with substitutions.  One substituted strand showing only a 5 degree drop in melting temperature compared to an unsubstituted control was deemed acceptable.  Another substituted strand showing a 15 degree drop was still deemed acceptable when the “degree of cooperativity” and “extent of hyperchromicity” were the same as the control.  These examples provided a “general guideline”: “when a linkage group is incorporated into a DNA strand having a length and sequence similar to those used in the specification, a decrease in Tm of up to 5 [degree] C implies that the linkage group does not `substantially interfere’ with hybridization, and a decrease of up to 15 [degree] C is acceptable if the degree of cooperativity and the extent of hyperchromicity are the same for the modified and unmodified strands.”
     e. PROSECUTION HISTORY; RESPONSE TO INDEFINITENESS REJECTION; EIGHT SPECIFIC LINKING GROUPS THAT DID NOT SUBSTANTIALLY INTERFERE.  The patents’ prosecution history was “helpful.”  A PTO examiner had rejected the claims on the ground that the “not interfering substantially” limitation was indefinite.  The patent owner overcame the rejection by submitting a declaration by its vice president, Engelhardt. The declaration listed eight “specific linkage groups” that did not substantially interfere.
     f. DETECTION DEFINITE FOR SAME REASONS AS HYBRIDIZATION.  Most of the above evidence, which was applicable to the definiteness of hybridization, was applicable to the definiteness of the “not interfering substantially” limitation.

5. ANTICIPATION: SUMMARY JUDGMENT NOT PROPER FOR SOME CLAIMS; PROPER FOR OTHER CLAIMS.  The district court’s grant of summary judgment of invalidity for anticipation by three prior art references was correct as to the asserted claims of one patent (‘928) but not as to those of the other two patents (‘824 and ‘767).
     a. BURDEN OF PERSUASION ON ACCUSED INFRINGER.  On a summary judgment motion attacking patent claim’s as invalid anticipation by prior art references, an accused infringer’s bears the burden persuasion.
          i. DETAILED CLAIM CHARTS; EXPERT DECLARATION.  Here, the accused infringer submitted (i) “detailed claim charts showing where each and every claim limitation is disclosed in the prior art,” and (ii) “an expert declaration explaining how the prior art meets those limitations under the district court’s claim construction.”
          ii. TWO REFERENCES: ARGUABLY WITHIN “EVEN MORE PREFERRED EMBODIMENTS”; THREE REPORT MOEITY A DETECTION.  Two of the accused infringer’s references disclosed linkage groups within the specification’s set of “even more preferred embodiments” because they were from a primary amine and had a CH2–NH structure.  Also, three of the references reported moeity A detection.
          iii.  PRIMA FACIE SHOWING; PATENT OWNER’S BURDEN TO SET OUT SPECIFIC FACTS SHOWING A GENUINE FACT ISSUE.  Based on its showing, the accused infringer “carried its initial burden of making a prima facie showing of anticipation.”  The burden shifted to the patent owner to set specific facts showing a genuine fact issue for trial.  Mere denials and conclusory statements would not suffice.
     b. KASAI REFERENCE; ‘824 AND ‘767 PATENT CLAIMS; EXPERT SHERMAN’S DECLARATION.  The district court granted summary judgment that the Kasai reference anticipated the asserted ‘824 and ‘767 patent claims.  This was error in view of the declaration the patent owner submitted by its expert, Sherman.
          i. KASAI GROUP:  SINGLE CARBON-CARBON BOND NOT SUFFICIENTLY RIGID TO PREVENT INTERFERENCE WITH HYBRIDIZATION.  The expert Sherman opined that the Kasai group was not sufficiently rigid to prevent significant interference with its single carbon-carbon bond.
          ii. ACCUSED INFRINGER: DISREGARD SHERMAN DECLARATION? INCONSISTENT WITH PRIOR DECLARATION SUBMITTED DURING PROSECUTION?  The accused infringer argued that the Sherman declaration did not create a fact issue because its assertion that a single bond structure was not sufficiently rigid was inconsistent  with a declaration (Engelhardt) the patent owner submitted during prosecution.  The Engelhardt declaration had included single bond structures as suitable linkage groups.  See Cleveland v. Policy Mgmt. Sys. Corp., 526 U.S. 795, 806 (1999).
          iii. UNDER SUMMARY JUDGMENT STANDARD, DECLARATION VIEWED MOST FAVORABLY TO OPPOSING PARTY (PATENT OWNER).  The standard for a summary judgment requires that the declaration and other evidence be viewed in a light more favorable to the party opposing summary judgement, here the patent owner.
           iv. SHERMAN’S EXPLANATION OF KASAI: LIMITED TO THAT PARTICULAR SINGLE BOND STRUCTURE; NOT BROAD CONDEMNATION OF ALL SINGLE BOND STRUCTURES; NO NECESSARY INCONSISTENCY.  In this light, the Sherman declaration must be read as only criticizing the specific single carbon group in Kasai and not as a broad condemnation of all single bond structures a suitable linkage group.
          v. TWO CHARACTERISTICS CONTRIBUTE TO INTERFERENCE: (1) BOND (SINGLE OR DOUBLE); (2) CHAIN LENGTH.  At least two characteristics of a linkage group can contribute to hybridization interference: the bond (single or double) and the chain’s length.  In his declaration, the expert Sherman focused on the bond, but the patent discussed both the bond and chain length.
          vi. KASAI STRUCTURE WITHIN PATENT’S “EVEN MORE PREFERRED” EMBODIMENT?  INFINITE VARIETY; SUBSET OF PREFERRED EMBODIMENT?  The accused infringer argued that the Kasai reference’s structure fell within the patent specification’s “even more preferred” category, that is, derived from a primary amine with a –CH2–NH– structure.  However, the patent indicated that there was “an infinite variety of linkage groups” in the category.  The patent owner read the “even more preferred” language as a “subset of preferred embodiments,” to wit, those with double bonds.  That reading is reasonable and must be credited on summary judgment.
     c. PINGOUD REFERENCE; ‘767 PATENT.  The district court granted summary judgment that the Pingoud reference anticipated the asserted ‘767 patent claims.  This was error because the Pingoud reference stated that its compound caused substantial interference with hybridization.  As with the Kasai reference, the accused infringer’s argument based on the patent’s “even more preferred” embodiment failed.
     d BAUMAN REFERENCE; ‘928 PATENT CLAIMS; ANTICIPATION IN VIEW OF CORRECT CLAIM CONSTRUCTION.  The district court granted summary judgment that the Bauman reference anticipated the asserted claims of the ‘928 patent.  This was correct, especially in view of a necessary correction in the district court’s interpretation of the claims.
           i. GLUTATHIONE AS LINKING GROUP; ATTACHMENT AFTER, NOT BEFORE, HYBRIDIZATION.  Bauman used as the linkage between moiety A and the base B a glutathione group.  Bauman disclosed attaching the linkage group after hybridization, unlike the embodiments disclosed in the ‘928 patent in which the attachment is before hybridization.
          ii. PATENT OWNER: CLAIMS REQUIRE THAT LINKAGE NOT INTERFERE WITH HYBRIDIZATION AFTER LABEL ATTACHED?  The patent owner argued that Bauman could not anticipate because ‘928 patent required that the linkage group not interfere with hybridization after the label was attached.
          iii. The argument lacked merit for two reasons.
               A. FIRST:  CLAIM TO PRODUCT, NOT PROCESS.  First, the claims are to a product, a “compound” with a formula-defined structure, not to a process.  For anticipation, how a claimed product is made is irrelevant.  In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985).
               B. SECOND, CLAIM IS SILENT ON HYBRIDIZATION; DISTRICT COURT ERROR IN CONSTRUING CLAIMS; ONLY DETECTION REQUIRED.  Second, the claims are silent as to hybridization.  The district court construed the claims as requiring no substantial interference with both hybridization and detection.  That was error because (1) the language of the claims required only that a linkage ground be “not interfering substantially with detection of A,” and (2) there was no clear disclaimer of claim scope in the specification or prosecution history.
           vi. IN BAUMAN, NO INTERFERENCE WITH DETECTION OF A.  The patent owner did not dispute that Bauman disclosed a linkage group that did not substantially interfere with detection of A.

6. CLAIM INTERPRETATION; FOURTH PATENT ON IMPROVEMENTS: 1988 FILING; CORRECT CONSTRUCTION OF “NON-RADIOACTIVE MOIETY”; INDIRECT DETECTION; NO INFRINGEMENT.  A fourth patent (‘830) claimed an improvement resulted from a 1988 application.  The district court correctly construed the claim phrase “non-radioactive moiety” as meaning a moeity used in indirect detection, that is, “a moiety that can be detected with a preformed detectable molecular complex.”
     a. TERM CANNOT HAVE LITERAL MEANING; COVERAGE OF ANY PIECE OF NATURAL DNA; INVALID ON FACE.  The phrase cannot have its literal meaning, which would broadly cover any piece of natural DNA and render “the claims invalid on their face.”
     b. PATENT OWNER:  “NON-RADIOACTIVE MOEITY” MEANS “NON-RADIOACTIVE DETECTION MOEITY,” THAT IS, LABEL, USABLE IN EITHER DIRECT OR INDIRECT DETECTION?  The patent owner argued that the disputed phrase should mean a “non-radioactive detection moeity”, which could be used in direct or indirect detection.
     c. CLAIM LANGUAGE; METHOD CLAIM 18 REQUIREMENT OF INDIRECT DETECTION; PRESUMPTION THAT TERM CARRIES SAME MEANING IN ALL CLAIMS.  That the “non-radioactive moiety” was simply a binding site for a preformed detectable molecular complex, with the complex, not the moiety generating a signal, was supported by the language of method claim 18 and the principle that claim terms presumptively carry the same meaning in all a patent’s claims.
i. Claim 18 was unambiguously limited to indirect detection.  It required “contacting [a] single stranded nucleic acid [target] under hybridizing conditions with (i) a [nucleotide] probe having at least one non-radioactive moeity … attached to each … end, said probe being capable of hybridizing to said target …, and (ii) a preformed detectable molecular complex; and detecting any hybridized complexes, thereby detecting the target nucleic acid sequence.”
ii. If the non-radioactive moeity generated a detectable signal (as in direct detection), there would have been no reason to contact it with the hybridized complex as the contact step’s part (ii) required.
iii. Also, what was detected was “hybridized complexes,” not the moiety.
iv. Therefore, at least for claim 18, it was clear that a “non-radioactive moeity” was “a moiety that can be detected with a preformed detectable molecular complex” (indirect detection).
v. CONSISTENT USAGE OF PHRASE IN ALL CLAIMS. The patent owner did not argue that the phrase (“non-radioactive moiety”) had a different meaning in claim 1 and 12 from that in claim 18.  Claims normally have a consistent meaning throughout a patent.
b. CLAIM DIFFERENTIATION.  The patent owner argued that the district court’s construction, which limited “non-radioactive moiety” to indirect detection, violated the doctrine of claim differentiation.  The argument lacked merit.
i. CLAIM 1.  Independent claim 1 recited:  “1. An oligo- or polynucleotide having at least one non-radioactive moiety directly or indirectly attached to each of the 5′ and 3′ end nucleotides thereof.”
          ii.  DEPENDENT CLAIM 14; CLAIM 1 NUCLEOTIDE AND A “PREFORMED DETECTABLE MOLECULAR COMPLEX.  Dependent claim 14 recited:  “14. A nucleic acid hybridization assay composition comprising an oligo- or polynucleotide of claims 1 or 12, and a preformed detectable molecular complex.”  (Emphasis added).
          iii. CONSTRUCTION: NON-RADIOACTIVE MOEITY CAN BE DETECTED WITH A PREFORMED DETECTABLE MOLECULAR COMPLEX.  The district court’s construction of “non-radioactive moiety” required that it ” `can be detected with a preformed detectable molecular complex.’  … (emphasis added).”
          iv. PATENT OWNER: CLAIMS 1 AND 14 RENDERED COEXTENSIVE?  The patent owner argued that that construction rendered claims 1 and 14 coextensive, a result contrary to the claim differentiation doctrine.
          v. CLAIM 1 BROADER, REQUIRING ONLY CAPABILITY OF DETECTION WITH A COMPLEX; CLAIM 14 REQUIRED ACTUAL PRESENCE OF THE COMPLEX.  However, claim 1, as construed, was broader than claim 14.  Claim 1 only required a capability of a detection with a complex.  Dependent claim 14 required the actual presence of the complex.
     c. SPECIFICATION:  NO DISCLOSURE OF DIRECT DETECTION.  The patent’s specification contained no disclosure of direct detection.  Thus, the specification did not support the patent owner’s broad disclosure.
          i. PREFERRED EMBODIMENTS NOT READ INTO CLAIMS.  The absence of a direct detection embodiment was not conclusive because courts do not read preferred embodiments into claims.  Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 913 (Fed. Cir. 2004).
          ii. Here, however, the claim language strongly suggested the narrower interpretation, an interpretation not precluded by the specification.
     d. PROSECUTION HISTORY.  The patent’s prosecution history undercut rather than supported the patent owner’s broad construction.
          i. During prosecution, in response to a prior art rejection, the patent owner argued that “no prior art reference ever taught or suggested the possibility of a nucleic acid hybridization assay composition comprising such a labelled oligo- or polynucleotide and a preformed detectable complex, e.g., a preformed avidin or streptavidin detectable molecular complex, as defined by the present claims.’ … (emphasis added).”
           ii. PATENT OWNER: “NON-RADIOACTIVE MOIETY” JUST A LABEL?  The patent owner argued that the statement equated “a `non-radioactive moiety’ with a `labeled oligo- or polynucleotide,’ which in turn suggests that the moiety is simply a `label.’ ”
          iii. HOW WAS THE “LABEL” DETECTED?  However, that argument did not resolve the question of how the “label” was detected.
          iv. The sentence as a whole suggested that detection was accomplished by the “preformed detectable complex.”
          v. The passage mentioned a biotin-avidin complex binding, which was an example of indirect detection.

1. On the definiteness requirement for claims, particularly in relation to the word “substantial,” see Chisum Patent Law Digest 2422, 2424, 5233; Chisum on Patents 8.03[3][c][vi].
2. On summary judgment in regard to anticipation, see Chisum Patent Law Digest 1245.
3. On claim interpretation, with illustrations in cases involving biotechnology, see Chisum Patent Law Digest 5229.12.  On claim differentiation, see Chisum Patent Law Digest 5240.

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