IMMUNOMEDICS, INC. v. THE BOARD OF DIRECTORS OF ROGER WILLIAMS MEDICAL CENTER et al

Filing 141

OPINION. Signed by Judge Jose L. Linares on 2/28/17. (DD, )

NOT FOR PUBLICATION
UNITED STATES DISTRICT COURT
DISTRICT Of NEW JERSEY
IMMUNOMEDICS, INC.,
Plaintiff,

Civil Action No.: 15-4526 (JLL)

OPINION
V.

ROGER WILLIAMS MEDICAL CENTER, et
cii.,
Defendant.

LINARES, District Judge.

This matter comes befoi-e the Court by way of an application for claim construction by
Plaintiff Immunornedics, Inc. and Defendants Dr. Richard P. Junghans, Dr. Steven C. Katz and
Roger Williams’ Medical Center. While this patent infringement action involves three separate
patents, the parties only seek construction of certain language contained in claims 1, 14, and 23 of
United States Patent No. 6,676,924 (“924 patent”) and claims 1 and 4 of United States Patent No.
6,926,893 (“893 patent”) (collectively, the “patents-in-suit”).1

The Court has considered the

parties’ written submissions (ECF Nos. 52, 63, 64, 98, 99) and the oral arguments advanced at the

Mathnan hearing which was held on January 23, 2017. (ECF No. 123).

The third patent-in-suit bears United States Patent No. 5,874,540 and does not contain the disputed term.
Accordingly, the said patent will not be discussed herein.

I.
A.

BACKGROUND

The Patents

The subject patents deal with, and relate to, the treatment of cancer and other infectious
diseases by utilizing specific antibodies to seek out and destroy the afflicted cells. (See Markman
Transcript at 7:259:16).2 The patents-in-suit claim a specific method of treating said illnesses by
utilizing a humanized antibody along with Chimeric Antigen Receptor T Cells (“CAR-I
Technology”). (See ECF Nos. 77-2, 77-2). To employ this method, Plaintiff “generated a DNA
that calls for [a specific antibody known as] humanized MN-14.” (Trans. at 13:24-25). Plaintiff
then asserts that humanized MN-14 (“hMN-14”) can be put into “viral vectors.” (Trans. at 14:12). A viral vector is a virus that can place new DNA into a cell; and in this case, specifically a T
Cell. (Trans at 8:14-17). Thereafier, the cell will generate hMN-14 on the surface. (Trans. at
14:2-3). Once this happens, the hMN-14 binds itself to the tumor and will destroy the cancer cell.
(Trans at 14:3-5).
The ‘924 Patent claims a “method for treating a patient comprising administering a
conjugate to said patient in an effective amount for treatment.” (See ECF No. 77-2 at 46, claim 1;
Trans. at 23:24-24:1). The conjugate here would include a conjugate of hMN-14 and a I Cell.
(Trans. at 24:1-3). Said differently, the ‘924 Patent claims methods treating or diagnosing patients
compromising administering a therapeutic or diagnostic agent bound to hMN-14. (See ECF No.
77 (“Compl.”) ¶f 189-90).
Plaintiffs ‘893 Patent claims a “method for inducing a cellular immune response in a
patient against a tumor that expresses carcinoembryonic antigen (CEA), said method comprising:
administering an effective immunostimulatory amount of transferred T cells to a patient; and

2

The Transcript from the January 23, 2017 Markman Hearing shall be cited as “Trans.” followed by the page and line
numbers, separated by a colon.

subsequently administering at least one cytokine to said patient.” (ECF No. 77-3 at 11, claim 1).
“[T]he ‘893 Patent talks about an effective amount of an effective immunostimulatory amount of
transfected T Cells to a patient.” (Trans. at 44:20-22). Thus, the ‘893 Patent claims methods for
introducing cellular immune response against a tumor that expressed CEA. (Compi.
B.

¶J 202-03).

Disputed Term and Proposed Construction

The parties have asked the Court to construe the term “effective amount.” “Effective
amount” is used three times in the ‘924 Patent and twice in the ‘893 Patent. In the ‘924 Patent
“effective amount” appears in Claims 1, 14 and 23. (ECF No. 77-2 at 46-48). Claim 1 of the ‘924
claims
A method for treating a patient comprising administrating a conjugate to
said patient in an effective amount for treatment, wherein said conjugate
comprises:
a therapeutic agent bound to a humanized Class III, anti
CEA, monoclonal antibody (mAb) or a fragment thereof,
wherein complementarily-determining regions (CDR5) of
said humanized mAb are CDRs from a parental murine Class
III, anti CEA mAb, wherein the light chain variable region
comprises CDRL1 comprising KASQDVGTSA (SEQ ID
NO:20), CDRL2 comprising WTSTRHT (SEQ ID NO: 21),
and CDRL3 comprising QQYSLYRS (SEQ ID NO:22), and
the heavy chain variable region comprises CDRH1
comprising TYWMS (SEQ ID NO:23), CDRH2 comprising
EIHPDS$TINYAP$LKD (SEQ ID NO:24), and CDRH3
comprising LYFGFPWFAY (SEQ ID NO:25), and each of
the framework regions (FRs) of the light and heavy chain
variable regions is from a human antibody, where said
humanized mAb retains the binding specificity of said
parental murine Class III, anti-CEA mAb.

(ECF No. 77-2 at 46)(emphasis added). Next, Claim 14 claims
A method for diagnosing a patient comprising administering a conjugate to
said patient in an effective amount for diagnosis, wherein said conjugate
comprises:
a diagnostic agent bound to a humanized Class III, 30 anti
CEA, monoclonal antibody (mAb) or a fragment thereof,
wherein the cornplernentarity-deterrnining regions (CDRs)

of said humanized mAb are CDRs from a parental murine
Class III, anti-CEA mAb, wherein the light chain variable
region comprises 35 CDRLI comprising KA$QDVGTSVA
(SEQ ID N0:20), CDRL2 comprising WTSTRHT (SEQ ID
N0:21), and CDRL3 comprising QQYSLYRS (SEQ ID
N0:22), and the heavy chain variable region comprises
CDRH1 comprising TYWMS (SEQ ID N0:23), 40 CDRH2
comprising EIHPDSSTNYAPSLKD (SEQ ID N0:24) and
CDRH3 comprising LYFGFPWFAY (SEQ ID N0:25), and
each of the framework regions (FRs) of the light and heavy
chain variable regions is from a human antibody, wherein
said humanized mAb 45 retains the binding specificity of
said parental murine Class III, anti-CEA mAb.
(ECF No. 77-2 at 47). Finally, Claim 23 claims
A method for treating a patient comprising administering a humanized Class
III, anti-CEA, monoclonal antibody (mAb) to said patient in an effective
amount for treatment, wherein said mAb comprises:
a humanized Class III, anti-CEA, monoclonal antibody
(mAb), wherein the complernentarity-determining regions
(CDR5) of said humanized mAb are CDRs from a parental
murine Class III, anti-CEA mAb or a fragment thereof,
wherein the light chain variable region comprises CDRLI
comprising KASQDVGTSVA (SEQ ID N0:20), CDRL2
comprising WTSTRHT (SEQ ID N0:21), and CDRL3
comprising QQYSLYRS (SEQ ID N0:22), and the heavy
chain variable region comprises CDRHI comprising
(SEQ.ID) N0:23),
TYWMS
CDRH2
comprising
EIHPDSSTNYAPSLKD (SEQ ID N0:24) and CDRH3
comprising LYFGFPWFAY (SEQ ID N0:25), and each of
the framework regions (FRs) of the light and heavy FRH4
comprises a region of 9-13 amino acids that occurs naturally
in the FRH4 of a human antibody.
(ECF No. 77-2 at 47-48)(emphasis added).
The ‘893 Patent utilizes the term “effective” in Claims 1 and 4. (ECF No. 77-3). Claim I
of the ‘893 patent claims
A method for inducing a cellular immune response in a patient against a
tumor that expresses carcinoembryonic antigen (CEA), said method
comprising:
administering an effective irnrnitnostimulatoiy amount of
transfected T cells to a patient; and subsequently
administering at least one cytokine to said patient; wherein

said transfected T cells are produced by obtaining T cells
from the patient and transfecting said T cells with an
expression vector to obtain said transfected T cells; wherein
said expression vector comprises a DNA molecule encoding
either a chimeric imrnunoglobulinlT cell receptor or a
chimeric irnrnunoglobulinlCD3 protein, and wherein said
immunoglobulin-encoding portion of said DNA molecule
encodes the variable regions of a Class III anti-CEA
antibody, wherein the Class III anti-CEA antibody is MN-14
or humanized MN-14, and further wherein the variable
regions of the u and 13 polypeptide chains of said T cell
receptor are replaced by said variable regions of the
antibody.

(ECF No. 77-3 at 1 1)(ernphasis added).
Claim 4 of the ‘893 patent claims
A method for inducing a cellular immune response in a patient against a
tumor that expresses carcinoembryonic antigen (CEA), said method
comprising:
administering an effective immunostirntdatoiy amount of
transfected T cells to a patient; and subsequently
administering at least one cytokine to said patient; wherein
said I cells are produced by obtaining T cells from the
patient and transfecting said I cells with an expression
vector to obtain said transfected T cells; wherein said
expression vector comprises a DNA molecule encoding
either a chimeric immunoglobulinlT cell receptor or a
chimeric immunoglobulinlCD3 protein, and wherein said
immunoglobulin-encoding portion of said DNA molecule
encodes the variable regions of an anti-idiotypic antibody
that recognizes a Class III anti-CEA antibody, wherein the
anti-idiotype antibody is W12, and further wherein the
variable regions of the C. and fpolypeptide chains of said T
cell receptor are replaced by said variable regions of the
antibody.

(ECF No. 77-3 at 11)(emphasis added). The parties agree that the term “immunostimulatory”
contained in Claim 1 of the ‘893 Patent is not subject to construction and that the only tenn that
the Court needs to construe in this claim is “effective amount.” (Trans. at 25:24-26:5).

Plaintiff proposes that this Court decline to construe the disputed term because Defendants
cannot show that the ten-n is indefinite, or, in the alternative, construe it as having its plain and
ordinary meaning. (See ECF No. 64 (“P1. Open. Br.”) at 13; ECF No. 98 (“P1. Rep. Br.”) at 10).
Moreover, Plaintiff asserts that, should the Court decline to construe the tenTi as having its plain
and ordinary meaning, that the Court should construe “effective amount” and “effective
immunostimulatory amount” to mean “an amount capable of producing [the claimed] result.”
(Trans. at 28:25-29:2). Defendants do not propose a construction. Rather, Defendants aver that
the disputed term is indefinite and the patents-in-suit are therefore invalid. (ECF No. 63 (“Def.
Open. Br.”) at 6-10); (ECF No. 99 (“Def. Rep. Br.”) at 10).
II.

LEGAL STANDARD

A court’s analysis of a patent infringement claim is two-fold. Tate Access Floors, Inc. v.
Interface Architectural Resources, Inc., 279 F.3d 1357, 1365 (Fed. Cir. 2002). The court must

first define the meaning and scope of the patent claims as a matter of law. Markman v. WesMew
Instruments, Inc., 52 F.3d 967, 978 (Fed. Cir. 1995) (en bane), aff’d, 517 U.S. 370 (1996). The
court then engages in a comparison of the claims as construed to the alleged infringing product or

method. Tate, 279 F.3d at 1365. At this stage, the Court must only engage in the first step.
Claim construction is a matter of law to be determined solely by the court. Phillips v. A WH
Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005), cert. denied, 546 U.S. 1170 (2006). “It 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.” Id. at 1312 (quotations omitted). In construing the terms of a patent,
a court should look first to the language of the claim itself Vitronics Corp. v. Conceptronic, Inc.,
90 F.3d 1576, 1582 (Fed. Cir. 1996). The terms in the claim “are generally given their ordinary
and customary meaning.” Id. at 1582. “[T]he ordinary and customary meaning of a claim term is
the meaning that the term 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, 415 F.3d at
1313. A court “must look at the ordinary meaning in the context of the written description and the
prosecution history.” Medrad, Inc. v. MRI Devices Corp., 401 F.3d 1313, 1319 (Fed. Cir. 2005).
The court should turn to “those sources available to the public that show what a person of skill in
the art would have understood disputed claim language to mean.” Innova/Pure Water, Inc. v.
Safari Water filtration Svs., Inc., 381 f.3d 1111, 1116 (Fed. Cir. 2004).
To this end, the court should first examine the intrinsic record—the patent itself, including
the claims, the specification and, if in evidence, the prosecution history. Vitronics, 90 F.3d at 1582
(citing Markman, 52 F.3d at 979). The specification “acts as a dictionary when it expressly defines
tenns used in the claims or when it defines terms by implication.” Id. Indeed, the Federal Circuit
has explained that the specification is “usually.

.

.

dispositive.

.

.

[and] the single best guide the

meaning of a disputed term.” Phillips, 415 F.3d at 1315 (quoting Vitronics, 90 F.3d at 1582). It
is “entirely appropriate for a court, when conducting claim construction, to rely heavily on the
written description for guidance as to the meaning of the claims.” Id. at 1317. The specification
is also an important guide in claims construction as it may contain “an intentional disclaimer, or
disavowal, of claim scope by the inventor.” Id. at 1316.
Additionally, the court should consult the patent’s prosecution history as it “provides
evidence of how the PTO and the inventor understood the patent.”

Id.

Courts should be

circumspect in reviewing a prosecution history as it represents “an ongoing negotiation between
the PTO and the applicant, rather than the final product of the negotiation.” Id. A district court
may also examine extrinsic evidence: “all evidence external to the patent and prosecution history.”
Markman, 52 F.3d at 980; Phillips, 415 F.3d at 1317-18 (stating that the Federal Circuit “ha[s]
authorized district courts to rely on extrinsic evidence”). Such evidence consists of testimony by
the inventor or by experts, dictionaries, and treatises. Markman, 52 F.3d at 980. In particular, a

court may find reference to technical dictionaries useful “in determining the meaning of particular
terminology.” See Phillips, 415 F.3d at 1318. However, extrinsic evidence is generally thought
to be less reliable than the patent and prosecution history, Id. at 13 18-19; in essence, it is “less
significant than the intrinsic record in determining the legally operative meaning of claim
language,” C.R. Bard, Inc. v. US. Surgical Coip., 388 f.3d 858, 862 (Fed. Cir. 2004)(quotation
omitted). With this framework in mind, the Court now turns to the disputed claim language.
Finally, a party may challenge the definiteness of the disputed tenm Should the Court find
the term indefinite the claim is rendered invalid. Nautilus, Inc. v. Biosig Instruments, Inc., 134
S.Ct. 2120, 2124-25 (2014). “A lack of definiteness renders invalid ‘the patent or any claim in
suit.” Nautilus, 134 S.Ct. at 2125 (quoting 35 U.S.C.

§ 282, ¶2(3)). The Federal Circuit recently

confirmed that an “[i]ndefiniteness [defense] must be proven by clear and convincing evidence.”
Sonix

Tech. Co., Ltd. V. Publications hit ‘1, Ltd.,

---

F.3d

,

*5 (Fed. Cir. 2017).

“indefiniteness analysis involves general claim construction principles.” Sonix,

---

F.3d

----

The
at *6

(citing Enzo Biochem, Inc. v. Applera Corp., 599 F.3d 1325, 1332 (Fed. Cir. 2010).
III.

ANALYSIS

As noted, Defendants have advanced an indefiniteness defense. Accordingly, the Court
will address this argument first. The

tenhl

“effective amount” is used in Claims 1, 14 and 23 of

the ‘924 Patent, and “effective immunostimulatory amount” is used in Claims 1 and 4 of the ‘893
Patent. As discussed, neither party disputes the meaning of the term “immunostimulatory,” and
agree that this term means to cause a person’s immune system to have a reaction. (Trans. at 25:2426:5). Thus, the only question before the Court is the meaning of “effective tenTi” as it appears in
the aforementioned patents.
$

Here, the Court finds that, based on both intrinsic and extrinsic evidence, the term
“effective amount” is not indefinite in either patent. The ‘924 Patents’ specification provides clear
guidance with regards to the term “effective amount.” There, the specification explains that “for
purpose of therapy, a humanized antibody conjugate and pharmaceutically acceptable carrier are
administered to a patient in a therapeutically effective amount.” (ECF No. 77-2 at col. 10, 11. 5356)(emphasis added). The specification goes on to explain that “[a] combination of a conjugate
and pharmaceutically accepted carrier is said to be administered in a ‘therapeutically effective
amount’ tf the amount administered is physiologically significant.”

(Id. at col. 10, 11. 53-

59)(emphasis added). According to the specification “[a]n agent is ‘physiologically significant’ if
its presence results in a detectable change in the physiology of a receipt patient.” (Id. at col. 10,
11. 59-61)(emphasis added). The specification also explains that “[a] targeted therapeutic agent is
‘therapeutically effective’ if it delivers a higher proportion of the administered dose to the intended
target that accretes at the target upon systemic administration of the equivalent untargeted agent.”
(Id. at col. 10, 11. 6 1-65). Accordingly, the ‘924 Patent’s specification contains a clear definition
and “acts as a dictionary [because] it expressly defines terms used in the claims.” Vitronics, 90
F.3d at 1582.
Similarly, the term is not indefinite in the ‘$93 Patent. Once again, the ‘893 Patent’s
specification contains a detailed definition for “therapeutically effective amount.”

The

specification explains that, “[flor purposes of therapy, antibodies or fragments are administered to
a mammal in a therapeutically efftctive amount.” (ECF No. 77-3, col. 13, 11. 43-45)(emphasis
added). “An antibody preparation is said to be administered in a ‘therapeutically effective amount’
if the amottnt administered is physiologically signflcant.
9

(ECF No. 77-3, col. 13, 11. 45-

47)(ernphasis added).

The specification further explains that “[a]n agent is physiologically

signIcant ifits presence results in a detectable change in the physiology ofa recipient mammal.”
(ECF No. 77-3, col. 1 3, 11. 47-49)(ernphasis added). Finally, the specification states that, “[i]n
particular, an antibody preparation of the present invention is physiologically signIcant

f its

presence invokes a httmoral and/or cellular immune response in the recipient mammal.” (ECF
No. 77-3, col. 13, 11. 49-52)(emphasis added). Once again, the Court finds that the term is not
indefinite. The specification of the ‘893 Patent contains a clear definition of what the term
“effective amount” means in the context of the invention.
Moreover, extrinsic evidence also shows that “effective amount,” as used in both the ‘924
and ‘$93 Patents, is not indefinite.

Specifically, Defendants themselves have used the term

“effective” in various publications. (Trans. 33:15-22). Plaintiff points to two articles authored by
Defendants Junghans and Katz wherein the subject technology is discussed and “effective” or
“efficacious” was utilized regarding said technology. In December 2008, Defendant Junghans
regarding the CEA technology. (See ECF No. 64-4 (RPJunghans, et al., Clinical Cancer Research
2008 December 15; 14(24): 8112-8122)). The purpose of the “report [was to] describe[] the

development and preclinical qualification tests of 2’’ generation (gen) anti-carcinoembryonic
(CEA) designer T Cells for use in human trial.” (Id. at 1). The report details the various tests
conducted and the results of said tests. (Id.). In the results section, Defendant Junghans and his
coauthors conclude that “2’ generation T cells were more effective in suppressing titmor in animal
models.” (Id.)(emphasis added). Hence, it is apparent that Defendant Junghans, a person of
ordinary skill in the art, has a clear understanding of the term “effective” as used in the context of
the patents-in-suit.
10

Defendant Katz also has an understanding of the term, as he too has coauthored literature
relating to the patents-in-suit. (ECF No. 64-5 (SC Katz, RP Jitnghans, et at. Cancer Gene Therapy

2016 23, 142-48)). The article begins by noting that “[m]etastatic spread of colorectal cancer
(CRC) to the peritoneal cavity is common and difficult to treat, with many patients dying from
malignant bowel obstruction.” (Id. at 1). Defendant Katz and Junghans, along with their other
coauthors, explain that they “are now studying intraperitoneal (IP) delivery of CAR-Ts for
peritoneal carcinomatosis.” (Id.). The article continues by stating that Defendants “have tested a
novel pre-clinical strategy for regional IP CAR-T delivery combined with the targeting of
suppressor cell populations in a murine model of PC.” (Id.). Defendants further note that they
“performed in vivo testing of IP CAR-T infusions in combination with suppressor cell depletion
or blockade” and that, after 14 days, “CAR-Ts atone signIcantly diminished the tumor burden

when compared with untreated mice.”

(Id. at 4)(emphasis added).

Thereafter, Defendants

conclude that “[t]he combination of CAR-Ts and anti-Gr-l was the most efficacious overatt” since
“[o]n day 14, there was no detectabte tumor found in any mouse that received the IP CAR-T.”
(Id.)(emphasis added). Therefore, it is apparent that both Defendants Katz and Junghans have an
explicit understanding of the term “effective amount” as it pertains to the patents-in-suit.
In conclusion, the Court finds that the term “effective amount” is not indefinite. The
specification of both patents continues an unambiguous definition of the term as it is used therein.
Moreover, both Defendants, who are extremely familiar with the subject technology, use the term
in their own scholarly articles and manuscripts. Defendants have failed to carry their burden in
showing that the term in dispute is indefinite by clear and convincing evidence. Thus, the term

11

“effective amount,” as used in the patents-in-suit, is not indefinite since a person of ordinary skill
in the art would have an obvious understanding of same.
Furthermore, the Court finds that the tenTi “effective amount” should be given its plain and
ordinary meaning which, in the context of the patents-in-suit, is consistent with Plaintiffs
proposed construction. As discussed, Defendants have not submitted any proposed construction
that is different and only

argue

that the ten-n is indefinite. The Court is cognizant that the Federal

Circuit has held that where “the plain and ordinary meaning of the disputed claim language is clear,
the district court [does] not err by declining to construe the claim term,” Sttmmit 6, LLC v. Samsung
Elecs. Co., $02 F.3d 1283, 1291 (Fed. Cir. 2015), in the case at bar, although the Court does find
that the ten-n at issue has a plain and ordinary meaning, it also finds that the plain and ordinary
meaning coincides with Plaintiffs proposed construction of”an amount capable of producing the
claimed result,” and hereby construes the term as such.
CONCLUSION

For the aforementioned reasons, this Court concludes that the term “effective amount” is
not indefinite and construes it to mean “an amount capable of producing the claimed result.”

DATED: Februaryc9017
JO

.L ARES
1frED STATES DISTRICT JUDGE

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