Vytacera Bio, LLC v. CytomX Therapeutics, Inc.

Filing 130

REPORT AND RECOMMENDATIONS regarding D.I. 102 MOTION for Claim Construction and D.I. 103 MOTION for Claim Construction. Please note that when filing Objections pursuant to Federal Rule of Civil Procedure 72(b)(2), briefing consists sole ly of the Objections (no longer than ten (10) pages) and the Response to the Objections (no longer than ten (10) pages). No further briefing shall be permitted with respect to objections without leave of the Court. Objections to R&R due by 10/21/2021. Signed by Judge Christopher J. Burke on 10/7/2021. (mlc)

IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF DELAWARE
VYTACERA BIO, LLC,
Plaintiff,
v.
CYTOMX THERAPEUTICS, INC.,
Defendant.

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Civil Action No. 20-333-LPS-CJB

REPORT AND RECOMMENDATION
In this patent infringement action filed by Plaintiff Vytacera Bio, LLC (“Plaintiff” or
“Vytacera”) against Defendant CytomX Therapeutics, Inc. (“Defendant” or “CytomX”),
presently before the Court is the matter of claim construction. (D.I. 102; D.I. 103) The Court
recommends that the District Court adopt the constructions set forth below.
I.

BACKGROUND
A.

Procedural Background

On March 4, 2020, Vytacera filed the instant action against CytomX in this Court. (D.I.
1) There are two patents-in-suit: United States Patent Nos. 8,809,504 (the “'504 patent”) and
9,775,913 (the “'913 patent” and collectively with the '504 patent, the “patents-in-suit”). (See
D.I. 1) United States District Judge Leonard P. Stark has referred this case to the Court to
resolve all pre-trial matters, up to and including the end of fact discovery (including the
resolution of claim construction proceedings). (D.I. 36)
Briefing with regard to claim construction was completed on July 9, 2021. (D.I. 58; D.I.
61) The Court conducted a Markman hearing by video conference on August 23, 2021
(hereinafter, “Tr.”).
B.

Factual Background

Vytacera is a Delaware corporation with its principal place of business in Portola Valley,
California, (D.I. 1 at ¶ 2), and it owns the rights to the '504 patent and the '913 patent, (id. at ¶¶
25, 32). CytomX is a Delaware corporation with its principal place of business in San Francisco,
California. (Id. at ¶ 3) It is a clinical-stage biopharmaceutical company that specializes in
cancer treatments, namely Probody® therapeutics. (Id.; D.I. 51 at 4) CytomX uses its Probody
technology platform to conduct basic research and identify and develop certain pharmaceutical
compounds. (D.I. 1 at ¶ 3)
Both of the patents-in-suit “relate[] to inhibitors that bind, inhibit, suppress, neutralize[]
or decrease activity of a biologically active agent.” (D.I. 1, ex. 1 (hereinafter, “'504 patent”)
Abstract; id., ex. 2 (hereinafter, “'913 patent”), Abstract) The '504 patent is entitled “Inhibitor
Which Is Deactivatable by a Reagent Produced by a Target Cell” and it issued on August 19,
2014. ('504 patent) The '913 patent is entitled “Method of Site Specific Activation of an
Antibody by a Protease” and it issued on October 3, 2017. ('913 patent) In essence, the '504
patent teaches specifics regarding the composition of the inhibitors that reduce the activity of a
biologically active agent, and the '913 patent teaches methods of their use. (D.I. 53 at 2; see also
'504 patent, col. 3:50-52) 1 These inhibitors can be “deactivated by an enzyme produced by
vertebrate cells” at the disease site, so that the biologically active agent is then released at the site
in an active form, such that it can have a therapeutic effect for a patient. (Id., col. 3:52-64) Both
patented inventions “can be used for treatment of a disease such as cancer, inflammatory[] or an
autoimmune disease.” (Id., col. 3:53-55)
Further details concerning the patents-in-suit will be addressed below in Section III.

1

The patents-in-suit share a specification, (D.I. 51 at 1 n.1), so unless otherwise
noted, when referring to the patents’ specifications, the Court will simply cite to the '504 patent.
2

II.

STANDARD OF REVIEW
It is well-understood that “[a] claim in a patent provides the metes and bounds of the right

which the patent confers on the patentee to exclude others from making, using, or selling the
protected invention.” Corning Glass Works v. Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1257
(Fed. Cir. 1989). Claim construction is a generally a question of law, although subsidiary fact
finding is sometimes necessary. Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 325-26
(2015).
The Court should typically assign claim terms their “‘ordinary and customary
meaning[,]’” which is “the meaning that the term[s] would have to a person of ordinary skill in
the art in question at the time of the invention, i.e., as of the effective filing date of the patent
application.” Phillips v. AWH Corp., 415 F.3d 1303, 1312-13 (Fed. Cir. 2005) (citations
omitted). However, when determining the ordinary meaning of claim terms, the Court should
not extract and isolate those terms from the context of the patent; rather it should endeavor to
reflect their “meaning to the ordinary artisan after reading the entire patent.” Id. at 1321; see
also Eon Corp. IP Holdings LLC v. Silver Spring Networks, Inc., 815 F.3d 1314, 1320 (Fed. Cir.
2016).
In proceeding with claim construction, the Court should look first and foremost to the
language of the claims themselves, because “[i]t is a bedrock principle of patent law that the
claims of a patent define the invention to which the patentee is entitled the right to exclude.”
Phillips, 415 F.3d at 1312 (internal quotation marks and citations omitted). For example, the
context in which a term is used in a claim may be “highly instructive.” Id. at 1314. In addition,
“[o]ther claims of the patent in question, both asserted and unasserted, can . . . be valuable” in
discerning the meaning of a particular claim term. Id. This is “[b]ecause claim terms are

3

normally used consistently throughout the patent, [and so] the usage of a term in one claim can
often illuminate the meaning of the same term in other claims.” Id. Moreover, “[d]ifferences
among claims can also be a useful guide[,]” as when “the presence of a dependent claim that
adds a particular limitation gives rise to a presumption that the limitation in question is not
present in the independent claim.” Id. at 1314-15.
In addition to the words of the claims, the Court should look to other intrinsic evidence.
For example, the Court should analyze the patent specification, which “may reveal a special
definition given to a claim term . . . that differs from the meaning [that term] would otherwise
possess” or may reveal an intentional disclaimer of claim scope. Id. at 1316. Even if the
specification does not contain such revelations, it “is always highly relevant to the claim
construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a
disputed term.” Id. at 1315 (internal quotation marks and citation omitted). That said, however,
the specification “is not a substitute for, nor can it be used to rewrite, the chosen claim
language.” SuperGuide Corp. v. DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed. Cir. 2004). And
a court should also consider the patent’s prosecution history, if it is in evidence, because it “can
often inform the meaning of the claim language by demonstrating how the inventor understood
the invention and whether the inventor limited the invention in the course of prosecution[.]”
Phillips, 415 F.3d at 1317.
Extrinsic evidence, “including expert and inventor testimony, dictionaries, and learned
treatises[,]” can also “shed useful light on the relevant art[.]” Id. (internal quotation marks and
citations omitted). Overall, while extrinsic evidence may be useful, it is “less significant than the
intrinsic record in determining the legally operative meaning of claim language.” Id. (internal

4

quotation marks and citations omitted); accord Markman v. Westview Instruments, Inc., 52 F.3d
967, 981 (Fed. Cir. 1995).
In utilizing these resources during claim construction, courts should keep in mind that
“[t]he construction that stays true to the claim language and most naturally aligns with the
patent’s description of the invention will be, in the end, the correct construction.” Renishaw PLC
v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998).
III.

DISCUSSION
In their briefing, the parties raised disputes about five different claim terms. The Court

subsequently ordered that resolution of the parties’ dispute as to one term (“recognition domain”)
would be deferred to a later stage of the case, because the parties’ briefing did not really get to
the heart of the real dispute as to that term. 2 (See Tr. at 238-39; see also D.I. 94; D.I. 106)
Below, then, the Court will recommend constructions for the four terms that are ready for
resolution now.
A.

“inhibitor”

The first disputed term, “inhibitor,” appears, inter alia, in claim 1 of the '504 patent, and
claims 1 and 22 of the '913 patent. Claim 1 of the '504 patent is representative for our purposes,
and is reproduced below:
1. An inhibitor which is deactivatable by a reagent produced by a
target cell comprising:
(a) a first moiety that binds, inhibits, suppresses,
neutralizes, or decreases activity of a biologically active
agent wherein said first moiety is operably linked to;

2

By the end of the Markman hearing, it seemed possible that the parties, now that
they understood the other side’s actual position as to the “recognition domain” term, might be
able to come to agreement on a construction. The Court ordered the parties to further meet and
confer on the issue. The parties did so, but were unable to agree. (D.I. 94)
5

(b) a second moiety specifically cleavable by a protease
produced by a target cell, wherein said first and second
moieties are not attached in nature and wherein specific
cleavage of said second moiety causes reduction of binding
activity of said inhibitor.
('504 patent, col. 83:11-20 (emphasis added)) The parties’ proposed constructions are below:
Term

Vytacera’s Proposal

CytomX’s Proposal

“inhibitor”

“a first and second moiety as
defined by the claim”

“a molecule, separate from the
[biologically active
agent/antibody], having the
ability to bind, inhibit,
suppress, neutralize, or
decrease activity of a
[biologically active
agent/antibody]”

(D.I. 43 at 6; see also D.I. 51 at 6 & n.3) 3
There is no dispute that there can be some type of connection (e.g., binding) between the
claimed inhibitor and the biologically active agent. (Tr. at 37-38) But the crux of the parties’
dispute is about whether the inhibitor can ever be a part of the same molecule as (i.e., be
“chemically link[ed]” or “chemically attached” in the same molecule with regard to) the
biologically active agent. See id. CytomX says it cannot, and that the inhibitor and the
biologically active agent must always be separate molecules; Vytacera disagrees and says that
the inhibitor and the biologically active agent can be a part of the same molecule. (D.I. 51 at 7;
D.I. 53 at 8; Tr. at 16, 19, 21-27, 33-35) For the following two reasons, the Court agrees with
CytomX.

3

The '913 patent’s claims state that the biologically active agent referenced therein
is an “antibody,” and so CytomX’s construction is to be read as reciting “antibody” instead of
“biologically active agent” with regard to those patent’s claims. (D.I. 51 at 6 n.3)
6

First, the claim language provides strong indication that an “inhibitor” and a biologically
active agent are separate entities that are not chemically attached. More specifically:
•

The '504 patent claims state that the “inhibitor” interacts with a
“biologically active agent,” ('504 patent, col. 83:11-14), and
the '913 patent claims state that the “inhibitor” interacts with an
“antibody” (which the parties agree is a biologically active
agent), ('913 patent, cols. 85:21-26, 86:56-60, 87:7-16; see also
Tr. at 30, 45). By using different words for these two terms,
the claims suggest that an “inhibitor” is a separate and distinct
entity from a “biologically active agent.”

•

This is also indicated by the reality that the inhibitor has a
component that takes action (i.e., “binds, inhibits, suppresses,
neutralizes, or decreases activity of”) that in turn affects the
biologically active agent. It is hard to conceive of how a first
entity (the inhibitor) could be said to “inhibit” or “suppress” or
“neutralize” a second entity (the biologically active agent), if
those two things were actually all part of the same chemical
molecule. Put another way (as CytomX noted in its briefing),
it seems nonsensical that the inhibitor could be part of the same
molecule of the very thing that it inhibits. (Cf. D.I. 51 at 9 (“A
unitary molecule that has one region that acts to inhibit another
region that is the biologically active agent being inhibited[]
would not function as an inhibitor.”) (emphasis in original); see
also Tr. at 35-36)

•

Nothing in the claims suggests that the inhibitor and
biologically active agent are chemically attached.

Second, the specification also supports CytomX’s proposal in various ways. In that
regard:
•

The first two sentences of the Abstract read: “The invention
relates to molecules inhibiting biologically active compounds
and further comprising moieties specifically cleavable by a
reagent produced by a target cell. The invention relates to
inhibitors that bind, inhibit, suppress, neutralize, or decrease
activity of a biologically active agent.” ('504 patent, Abstract
(emphasis added)) This wording strongly suggests that
inhibitors are stand-alone “molecules” and that they inhibit
separate “molecules” (the “biologically active compounds,”
which is a synonym for “biologically active agents”).
7

•

The specification describes the “[i]nhibitor-ligand pair” 4 as a
“set of molecules that demonstrate specific binding[.]” ('504
patent, col. 5:36-37 (emphasis added); see also D.I. 51 at 10;
D.I. 61 at 2) The reference to a “set of molecules” again
denotes that this “pair” being described must amount to more
than one molecule—not that the inhibitor and the ligand are
part of the same molecule.

•

Vytacera’s counsel acknowledged that all of the examples
described in the specification discuss how the inhibitor and
biologically active agent are bound together, but do not discuss
the two entities being chemically attached in the same
molecule. (Tr. at 107)

For the above reasons, the term “inhibitor” should be construed to mean “a molecule,
separate from the [biologically active agent/antibody], having the ability to bind, inhibit,
suppress, neutralize, or decrease activity of a [biologically active agent/antibody].”
B.

“inhibitor is administered alone or together with said antibody”

The second disputed term, “inhibitor is administered alone or together with said
antibody” appears, inter alia, in claims 1 and 22 of the '913 patent, which are reproduced below:
1. A method of site specific activation of an antibody comprising
administration of an inhibitor which is deactivatable by a protease
produced by a target cell comprising:
(a) a first moiety that binds, inhibits, suppresses,
neutralizes, or decreases activity of said antibody wherein
said first moiety is operably linked to
(b) a second moiety comprising a polypeptide specifically
cleavable by said protease produced by said target cell,
wherein said first and second moieties are not attached in
nature and wherein specific cleavage of said second moiety
causes reduction of binding, inhibiting, suppressing, or
neutralizing activity of said inhibitor and restoration of
activity of said antibody;

4

The specification notes that the terms “ligand” and “[b]iologically active agent”
“can be used interchangeably[.]” ('504 patent, col. 5:45-47; see D.I. 61 at 2 n.2)
8

said inhibitor is administered alone or together with said
antibody such that the activity of said antibody is reduced
until it reaches said target cell producing said protease
wherein the inhibitor is cleaved by said protease and
activity of said antibody is restored.
...
22. A method of site specific activation of a monoclonal antibody,
a bispecific antibody and a single chain antibody or a combination
thereof comprising administration of an inhibitor which is
deactivatable by a reagent produced by a target cell comprising:
(a) a first moiety that binds, inhibits, suppresses,
neutralizes, or decreases activity of said monoclonal
antibody, bispecific antibody and single chain antibody or a
combination thereof wherein said first moiety is operably
linked to
(b) a second moiety comprising a polypeptide specifically
cleavable by said reagent comprising a protease produced
by said target cell, wherein said first and second moieties
are not attached in nature and wherein specific cleavage of
said second moiety causes reduction of binding, inhibiting,
suppressing, or neutralizing activity of said inhibitor and
restoration of activity of said monoclonal antibody,
bispecific antibody and single chain antibody or a
combination thereof;
said inhibitor is administered alone or together with said
monoclonal antibody, bispecific antibody and single chain
antibody or a combination thereof such that the activity of
said monoclonal antibody, bispecific antibody and single
chain antibody or a combination thereof is reduced until it
reaches said target cell producing said reagent wherein the
inhibitor is cleaved by said reagent and activity of said
monoclonal antibody, bispecific antibody and single chain
antibody or a combination thereof is restored.
('913 patent, cols. 85:22-39, 86:55-87:16 (emphasis added)) The parties’ proposed constructions
are below:
Term

Vytacera’s Proposal

9

CytomX’s Proposal

“inhibitor is administered
alone or together with said
antibody”

“[i]nhibitor can be attached to
the antibody or not attached to
the antibody”

“inhibitor [as construed] is
administered by itself, i.e., not
with said antibody, or inhibitor
[as construed] is coadministered with said
antibody”

(D.I. 43 at 8)
The dispute as to this term is an offshoot of the dispute regarding the construction of
“inhibitor.” The import of Vytacera’s proposal here was (again) to obtain a construction that
makes it clear that in some circumstances, an inhibitor can be “attached” (i.e., chemically
attached, as part of the same molecule) to the antibody (i.e., the biologically active agent). (D.I.
53 at 11-12; D.I. 58 at 5-6; D.I. 61 at 7; see also Tr. at 83 (Vytacera’s counsel noting that the
dispute over this term involves “everything that we’ve been arguing previously [as to the
‘inhibitor’ term]”)) For the reasons set out above regarding the “inhibitor” term, the Court has
explained why this is incorrect. Nor does it make any sense to the Court to have that “chemical
attachment” fight with regard to this particular claim term, which is about the entirely different
concept of “administ[ration]” of the inhibitor and biologically active agent. (Tr. at 92-93
(CytomX’s counsel noting that “it doesn’t make sense to take the word ‘administered’ . . . and to
convert it into kind of a compositional feature of attachment”)) So for all of these reasons, the
Court rejects Vytacera’s proposed construction.
If “administering [the inhibitor] . . . together with” the antibody does not mean that the
two can be chemically attached, then what does that language mean? In the Court’s view,
CytomX is correct to say that it means that the inhibitor is simply “co-administered with [the]
antibody.” The '913 patent specification says that “[i]n [a] preferred embodiment of the
invention, the inhibitor is administered alone, co-administered with an active agent, or co[]administered with an active agent and an adjuvant, a pharmaceutically acceptable carrier, a
10

diluent, or an excipient to a vertebrate.” ('913 patent, col. 14:59-63 (emphasis added); see D.I.
51 at 12) And other portions of the specification emphasize that when two substances are
administered “together,” or co-administered, that just means that the two substances are provided
to a patient “in combination with” each other in some way. ('913 patent, col. 37:4-5; see also id.,
cols. 5:44-48; 33:53-55)
For the above reasons, then, the term “inhibitor is administered alone or together with
said antibody” should be construed to mean “inhibitor is administered by itself, i.e., not with said
antibody, or inhibitor is co-administered with said antibody.”
C.

“reduction of binding activity of said inhibitor”

The third disputed term, “reduction of binding activity of said inhibitor,” appears, inter
alia, in claim 1 of the '504 patent. The claim is reproduced again here:
1. An inhibitor which is deactivatable by a reagent produced by a
target cell comprising:
(a) a first moiety that binds, inhibits, suppresses,
neutralizes, or decreases activity of a biologically active
agent wherein said first moiety is operably linked to;
(b) a second moiety specifically cleavable by a protease
produced by a target cell, wherein said first and second
moieties are not attached in nature and wherein specific
cleavage of said second moiety causes reduction of binding
activity of said inhibitor.
('504 patent, col. 83:11-20 (emphasis added)) The parties’ proposed constructions are below:
Term

Vytacera’s Proposal

CytomX’s Proposal

“reduction of binding
activity of said inhibitor”

“[i]nhibition, suppression, or
neutralizing activity of the
inhibitor is reduced, lowered,
or removed”

“a reduction in the inhibitor’s
ability to bind a biologically
active agent”

(D.I. 43 at 4-5)

11

The crux of the dispute here is whether “reduction of binding activity” only dictates
reduction of binding activity (as CytomX proposes), or whether (as Vytacera proposes) it also
requires diminution of the inhibition, suppression or neutralizing activity of the inhibitor. In
Vytacera’s view, “binding” is basically a synonym for “inhibition, suppression, or neutralizing
activity[,]” (Tr. at 113, 120), and so when the term-at-issue requires a “reduction of binding
activity,” that necessarily means not only a “reduction of binding activity” but also a reduction of
“inhibition, suppression, or neutralizing activity.” In CytomX’s view, however, there is a
difference between the “concepts of binding on the one hand,” and “the other words of activity
used in the claim [like] inhibit[s], suppress[es and] neutralize[s.]” (Id. at 121; see also id. at 12324) 5
Looking first at the words of claim 1, we see that limitation (a) uses the conjunction “or”
in describing how the first moiety interacts with the biologically active agent. The use of “or”
would typically indicate that the first moiety “binds” the agent, or “inhibits” the agent, or
“suppresses” the agent, or “neutralizes” the agent or “decreases activity of” the agent, or that it
can do more than one or all of these things—but it would not typically suggest that the first
moiety is required to do any more than one of these things. That said, limitation (b) requires that
cleavage of a second moiety causes reduction of the “binding activity” of the inhibitor. In light
of that language in limitation (b), both parties agree the first moiety is at least required to bind a
biologically active agent. (D.I. 51 at 13; Tr. at 121, 126-27, 131, 142)

5

This is because, in CytomX’s view, while binding “implies necessarily a decrease
in activity or a suppression of activity” or a neutralization of activity in a certain way, a moiety
may also inhibit or suppress or neutralize activity in a “different way than binding” does. (Tr. at
128) In other words, to CytomX, “inhibits, suppresses, [and] neutralizes” are broader terms than
binding, vis-à-vis the inhibitor’s impact on a biologically active agent.
12

From there, in the Court’s view, the fact that the claim uses separate terms for “binds,”
“inhibits,” “suppresses,” “neutralizes,” or “decreases activity” indicates to the Court that those
are each at least somewhat different processes, and that (contrary to Vytacera’s position) they do
not all have the exact same meaning. See Helmsderfer v. Bobrick Washroom Equip., Inc., 527
F.3d 1379, 1382 (Fed. Cir. 2008) (“Our precedent instructs that different claim terms are
presumed to have different meanings.”). And because of the use of the word “or” in limitation
(a), even though the first moiety is required to bind a biologically active agent, it does not appear
that the moiety is also necessarily required to inhibit, or suppress, or neutralize or decrease the
activity of the agent (at least to an extent different from what occurs during “binding” activity).
The claim seems to allow that the first moiety can do one or more of those things in addition to
binding with the agent, but that it is not required to do any of them. And so, when it comes to
the term in question, Vytacera’s proposal appears to contravene the claim language—in that it
would require that cleavage of the second moiety cause not only reduction of binding activity
(i.e., the kind of reduction specifically called out by the claim term itself), but also an additional
type of reduction of inhibition, suppression or neutralizing activity, when the claim does not
actually require that any such additional activity would have been occurring in the first place.
In addition to the claim language, the '504 patent’s prosecution history provides some
support to CytomX’s position. In response to an Office Action—wherein the Examiner had
rejected the proposed claims pursuant to 35 U.S.C. §§ 102 & 103 in light of prior art including
“Thorpe et al.”—the patentee amended limitation (b) in claim 1. (D.I. 43, ex. 1) In doing so, the
patentee removed the terms “inhibiting, suppressing, or neutralizing” from that part of the claim,
as follows:
(b) a second moiety specifically cleavable by a protease reagent
produced by a target cell, wherein said first and second moieties
13

are not attached in nature and wherein specific cleavage of said
second moiety causes reduction of binding, inhibiting, suppressing,
or neutralizing activity of said inhibitor.
(Id. at Appx0008 (alteration and emphasis in original)) In further explaining his position, the
patentee responded to the Examiner’s rejection by noting, inter alia, that:
Thorpe et al. disclose[s] a site specific delivery of a coagulant
using an antibody. Thorpe et al. does not disclose “a specific
cleavage of said second moiety causes reduction of binding
activity of said inhibitor to its target.” Thorpe et al. fusion protein
constructs are cleaved without affecting the protein activity or the
binding activity.
(D.I. 43, ex. 1 at Appx0003 (regarding 35 U.S.C. § 102 rejection); see also id. (regarding 35
U.S.C. § 103 rejection)) It is hard to tell for sure what was in the patentee’s mind here, or how
or whether the patentee felt that striking “inhibiting, suppressing, or neutralizing activity” from
limitation (b) helped underscore why the present invention should be distinguished from Thorpe
et al. 6 But in the end, the effect of the amendment seems to be that after cleavage, no associated
reduction of “inhibiting, suppressing, or neutralizing” activity (other than what may occur due to
a reduction in binding activity) is relevant to the claim’s scope. 7 (Tr. at 133) And so (as

6

During the Markman hearing, Vytacera’s counsel suggested that in distinguishing
the claim from Thorpe et al. during prosecution, the only thing that the patentee was trying to
convey to the Examiner was that in Thorpe et al. “nothing happened with the cleavage[,]” while
in the patented invention “once you cleave the inhibitor, it has a reduction of binding activity.”
(Tr. at 115) But the Court then followed up by asking counsel why—if all the patentee was
trying to do was to make that point—did the patentee remove the words “inhibiting, suppressing,
or neutralizing” from the claim? (Tr. at 116) After all, if those words are simply synonyms for
“binding,” as Vytacera suggests, then there would seem to be no reason to remove them from the
claim—since their presence in the claim would not interfere with the point the patentee was
trying to make. Vytacera’s counsel did not have an answer to that question. (Id.)
7

The Court need not decide if this evidence is so clear and unmistakable to amount
to prosecution disclaimer. TC Tech. LLC v. Sprint Corp., 379 F. Supp. 3d 305, 325 (D. Del.
2019). The Court simply cites to it as another piece of persuasive evidence indicating that
CytomX’s proposed construction is correct.
14

Vytacera’s counsel acknowledged during the Markman hearing), its proposed construction
amounts to an effort to re-insert into the claim the very thing that the patentee struck from the
claim during prosecution. (Tr. at 140-41) That seems inappropriate.
For the reasons set out above, Vytacera’s proposed construction should not be adopted.
Having said that, the Court does not think that adopting CytomX’s proposed construction is
necessary either. CytomX’s proposal simply repositions the words of the claim term, which will
not be helpful to the factfinder. (D.I. 58 at 6) Thus, having resolved the parties’ dispute here,
the Court will not recommend a new construction. Instead, it simply recommends that
“reduction of binding activity of said inhibitor” be afforded its plain and ordinary meaning.
D.

“biologically active agent”

The fourth and final disputed term, “biologically active agent” also appears in claim 1 of
the '504 patent. One more time, that claim reads:
1. An inhibitor which is deactivatable by a reagent produced by a
target cell comprising:
(a) a first moiety that binds, inhibits, suppresses,
neutralizes, or decreases activity of a biologically active
agent wherein said first moiety is operably linked to;
(b) a second moiety specifically cleavable by a protease
produced by a target cell, wherein said first and second
moieties are not attached in nature and wherein specific
cleavage of said second moiety causes reduction of binding
activity of said inhibitor.
('504 patent, col. 83:11-20 (emphasis added)) The parties’ proposed constructions are below:
Term

Vytacera’s Proposal

CytomX’s Proposal

“biologically active agent”

“[m]olecules that regulate the
immune response to disease
cells including stimulation of
cells to secrete immuneaugmenting cytokines,

“biologically active compound,
which is a separate molecule
from the inhibitor”

15

chemokines, an inhibitory
peptide”
(D.I. 43 at 3)
The Court first examines CytomX’s proposed construction. That proposal imports the
phrase “biologically active compound,” which the parties all agree means the same thing as
“biologically active agent.” (Tr. at 160-61, 176-77) In the Court’s view, this part of CytomX’s
construction could be confusing, because it might suggest that “biologically active compound” is
the only synonym for “biologically active agent” used by the patents. In fact, that is not so, as
the patents also use other terms (like “ligand”) to mean “biologically active agent.” (See, e.g.,
'504 patent, col. 5:45-47) So the Court is not going to adopt that part of CytomX’s proposal.
The only remaining part of CytomX’s proposal relates to the chemical “separateness” of
the inhibitor from the biologically active agent. (D.I. 51 at 15) The Court has already resolved
that dispute above in addressing the term “inhibitor.” There is no need to do so again here by
importing this additional proposed language (i.e., “which is a separate molecule from the
inhibitor”) into a new construction of “biologically active agent.”
This is all a way of saying that the Court does not find CytomX’s proposal very helpful in
resolving the parties’ true dispute over this term. Vytacera’s proposal does at least engage with
that dispute, and the Court addresses it next.
Vytacera’s proposal is taken from the following excerpt in the specification:
Biologically active agent, active agent, (biologically) active
compound, biological response modifier, or ligand (can be used
interchangeably): Are molecules that regulate the immune
response to disease cells including stimulation of cells to secrete
immune-augmenting cytokines, chemokines, a[n] inh[i]bitory
peptide, molecules like interleukines (IL), IL-1, IL-2, GM-CSF,
IFN, and IL-12, colony stimulating factor (CSF), GM-CSF,
interleukins, interferons, colony stimulating factors, a coagulation
factor, a fibrinolytic protein, a photosensitizing agent, or an
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imaging agent, a biological activation cascade or a component of
this cascade, a component of the coagulation system, a component
of fibrinolysis system, a component of the complement system, the
kinin system, an enzyme which converts the inactive precursor of a
pharmacological substance into the pharmacologically active
substance, antibodies, peptides, muteins of the above, a
pharmacologically active substance, macromolecular drugs,
chemical drugs, and the like are contemplated.
('504 patent, col. 5:45-62 (emphasis added)) Vytacera considers this block quote (hereafter, “the
block quote”) to be a definition of “biologically active agent”; it urges the Court to adopt only
the portion of that asserted definition that is italicized above. But the Court does not think it
should do so, for a few reasons.
As an initial matter, while the above-excerpted block quote does seem an attempt by the
patentee to explain what a “biologically active agent” can be, the Court is not convinced that
Vytacera’s proposal (which reproduces only a portion of that block quote) is faithful to the
meaning of this text. Vytacera’s position is that the block quote is meant to explain that
“biologically active agents” are all “molecules that regulate the immune response to disease
cells”; it argues that everything listed after this wording in the block quote are simply examples
of molecules that regulate the immune response. (Tr. at 149, 151, 155, 187-89) The Court,
however, is not sure that is correct. For example, CytomX’s counsel argued that one of those
listed agents—“photosensitizing agents”—do not regulate the immune response to disease cells.
(D.I. 51 at 16; Tr. at 180-81) In its briefing, CytomX pointed to a portion of the specification
that describes these photosensitizing agents; that text seems to focus on how such agents absorb
light and transfer absorbed energy to oxygen molecules in tissue. (D.I. 51 at 16 (citing '504

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patent, col. 32:10-28)) The text does not appear to indicate (at least facially) that such agents in
fact regulate an immune response. (Id.) 8
Instead, the Court believes that CytomX’s reading of the block quote is the better one.
CytomX asserts that the block quote is simply delineating exemplary biologically active agents
(that is, agents that have some biological activity on living matter), and that it does so, for the
most part, by listing various such agents and setting them off by commas. (Tr. at 178-79) In
other words, CytomX reads this listing as follows:
Biologically active agent, active agent, (biologically) active
compound, biological response modifier, or ligand (can be used
interchangeably): Are[:]
[(1)] molecules that regulate the immune response to disease cells
including stimulation of cells to secrete immune-augmenting
cytokines,
[(2)] chemokines,
[(3)] a[n] inhibitory peptide,
[(4)] molecules like interleukines (IL), IL-1, IL-2, GMCSF, IFN, and IL-12,
[(5)] colony stimulating factor (CSF),
[(6)] GM-CSF,
[(7)] interleukins,
[(8)] interferons,
[(9)] colony stimulating factors,

8

During the Markman hearing, Vytacera’s counsel stated that it would point the
Court to text in the specification that showed that a photosensitizing agent does affect the
immune response to disease cells. (Tr. at 189-90) But its counsel ended up citing to the same
portion of the specification that CytomX pointed to (discussed above). (Id. at 195) And the
Court did not understand Vytacera’s counsel’s argument as to how that part of the specification
supported Vytacera’s argument. (Id.) There might be other evidence that suggests that Vytacera
is right here, but Vytacera has not presented it to the Court.
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[(10)] a coagulation factor,
[(11)] a fibrinolytic protein,
[(12)] a photosensitizing agent, or an imaging agent, 9
[(13)] a biological activation cascade or a component of
this cascade,
[(14)] a component of the coagulation system,
[(15)] a component of fibrinolysis system,
[(16)] a component of the complement system,
[(17)] the kinin system,
[(18)] an enzyme which converts the inactive precursor of a
pharmacological substance into the pharmacologically
active substance,
[(19)] antibodies,
[(20)] peptides,
[(21)] muteins of the above,
[(22)] a pharmacologically active substance,
[(23)] macromolecular drugs,
[(24)] chemical drugs,
[(25)] and the like are contemplated.
(See '504 patent, col. 5:45-62) This interpretation seems sensible. And it does not appear
disputed that all of the above-listed substances would at least qualify as agents that have some
biological activity (i.e., “biologically active agents”).
Another point in favor of CytomX’s position is that, in other portions of the specification
that describe preferred embodiments, the patent clearly states that substances including
“vitamins” and “toxins” are also biologically active agents. ('504 patent, col. 27:36-59 (noting
9

According to Vytacera’s counsel, these are one in the same. (Tr. at 188-89)
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that “vitamins” are an example of “ligands”); id., cols. 5:65-6:1, 28:49-50 (stating that “toxins”
are “active agents” and that they are inhibited by an inhibitor)) This would be in harmony with
CytomX’s reading of the block quote, since at the end of that quote, the patent notes that the
above list of biologically active agents is not exclusive (by using the wording “and the like”).
('504 patent, col. 5:62) But it would not jibe with Vytacera’s reading of the block quote. During
the Markman hearing, Vytacera’s counsel confirmed that in Vytacera’s view, “vitamins” and
“toxins” are not biologically active agents and would not fit within the confines of its proposed
construction. (Tr. at 157-59) That simply indicates to the Court that Vytacera’s proposed
construction must be wrong—because it would directly contradict those portions of the
specification that say that “vitamins” and “toxins” are biologically active agents.
So the Court has clearly resolved the dispute as to Vytacera’s proposed construction—by
rejecting it. And it has explained why it found CytomX’s proposed construction unhelpful. In
light of this, and because the meaning of the term-at-issue seems not hard to discern (it is an
agent, that has some amount of biological activity), (D.I. 51 at 15; Tr. at 172-73; ('504 patent,
cols. 3:57-58, 83:13), the Court recommends that “biologically active agent” simply be afforded
its plain and ordinary meaning.
IV.

CONCLUSION
For the foregoing reasons, the Court recommends that the District Court adopt the

following constructions:
1. “inhibitor” should be construed to mean “a molecule, separate from the [biologically
active agent/antibody], having the ability to bind, inhibit, suppress, neutralize, or
decrease activity of a [biologically active agent/antibody]”;

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2. “inhibitor is administered alone or together with said antibody” should be construed
to mean “inhibitor is administered by itself, i.e., not with said antibody, or inhibitor is
co-administered with said antibody”;
3. “reduction of binding activity of said inhibitor” should be afforded its plain and
ordinary meaning; and
4. “biologically active agent” should be afforded its plain and ordinary meaning.
This Report and Recommendation is filed pursuant to 28 U.S.C. § 636(b)(1)(B), Fed. R.
Civ. P. 72(b)(1), and D. Del. LR 72.1. The parties may serve and file specific written objections
within fourteen (14) days after being served with a copy of this Report and Recommendation.
Fed. R. Civ. P. 72(b)(2). The failure of a party to object to legal conclusions may result in the
loss of the right to de novo review in the district court. See Sincavage v. Barnhart, 171 F. App’x
924, 925 n.1 (3d Cir. 2006); Henderson v. Carlson, 812 F.2d 874, 878-79 (3d Cir. 1987).
The parties are directed to the Court’s Standing Order for Objections Filed Under Fed. R.
Civ. P. 72, dated October 9, 2013, a copy of which is available on the District Court’s website,
located at http://www.ded.uscourts.gov.

Dated: October 7, 2021

Christopher J. Burke
UNITED STATES MAGISTRATE JUDGE

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