biomodal Limited et al v. New England Biolabs, Inc.

Filing 78

Judge Richard G. Stearns: ORDER entered granting in part and denying in part 54 Motion to Dismiss for Failure to State a Claim; finding as moot 66 Motion to Strike ; denying 7 Motion for Preliminary Injunction. Counts I, II, and III are dismissed. Defendant's response to the remaining counts of the Complaint is due in fourteen (14) days. (RGS, law3)

UNITED STATES DISTRICT COURT
DISTRICT OF MASSACHUSETTS
CIVIL ACTION NO. 24-11697-RGS
BIOMODAL LIMITED and CHILDREN’S
MEDICAL CENTER CORPORATION
v.
NEW ENGLAND BIOLABS, INC.
MEMORANDUM AND ORDER ON
PLAINTIFFS’ MOTION FOR A
PRELIMINARY INJUCTION and
DEFENDANT’S MOTION TO DISMISS
November 25, 2024
STEARNS, D.J.
Plaintiffs biomodal Limited (biomodal) and Children’s Medical Center
Corporation (CMCC) filed this action against defendant New England
Biolabs, Inc. (NEB), accusing it of infringing U.S. Patent Nos. 10,337,053 B2
(’053 patent); 10,443,091 B2 (’091 patent); 10,533,213 B2 (’213 patent);
10,731,204 B2 (’204 patent); 10,774,373 B2 (’373 patent); 10,767,216 B2
(’216 patent); 11,072,818 B2 (’818 patent); and 11,208,683 B2 (’683 patent).
Before the court are two motions: (1) plaintiffs’ motion for a preliminary
injunction prohibiting NEB from marketing allegedly infringing products;
and (2) defendant’s motion to dismiss the claims of the ’204, ’213, ’818, ’373
and ’683 patents as embodying unpatentable subject matter under 35 U.S.C.

§ 101. 1 For the following reasons, the court will allow in part and deny in part
the motion to dismiss and deny the motion for a preliminary injunction.
MOTION TO DISMISS
I.

The Patents
Epigenetics is the study of changes in gene expression that are not

encoded in DNA – in other words, how environmental and behavioral factors
impact the function of genes without changing the underlying sequence of
the DNA.

One of the most common epigenetic modifications is the

methylation of DNA. This is often performed by using 5-azacytidine, one of
the several analogs for the nucleoside cytidine, to create 5-methylcytosine
(5mC). 5mC may further be oxidized into 5-hydroxymethylcytosine (5hmC).
5mC and 5hmC occur naturally and are often associated with diseases
like cancer, making detection and quantification of these modifications
medically significant. The asserted patents, which share substantially the
same specification and claim priority to the same provisional application,
address this issue. They are directed to “novel methods for regulating and
detecting the cytosine methylation status of DNA.” ’213 patent, abstract.

1 NEB does not move to dismiss the claims of the ’053, ’091, or ’216

patents.

2

NEB challenges the following claims from the asserted patents: 2
’818 patent
1. A method comprising contacting with, or delivering to a
nucleic acid sequence, an enzyme or fragment thereof that
oxidizes at least one methylated DNA base, in an amount
effective
to
convert
5-methylcytosine
to
5hydroxymethylcytosine.
’204 patent
1. A method of converting a methylated cytosine residue in an
isolated nucleotide sequence to a modified base, the method
comprising:
contacting said isolated nucleotide sequence with an enzyme or
a catalytically active fragment thereof that converts said
methylated cytosine residue in said isolated nucleotide sequence
to said modified base, wherein said modified base comprises a
hydroxymethylated cytosine residue,
wherein said enzyme or said catalytically active fragment thereof
comprises TET1, TET2, TET3, CXXC4, a catalytically active
fragment of any of these, or any combination thereof.
...

2 The court declines, at this early stage in the litigation, to find the

recited claims representative of their respective patents. Plaintiffs identify
additional limitations which could possibly render some of the remaining
claims eligible, and in any event, these claims are not currently asserted in
this action and are thus not before the court. Should that change – if, for
example, plaintiffs move for leave to amend the Complaint to add back the
dismissed counts under the aegis of a different claim – it remains open to
NEB to oppose on the grounds that the newly asserted claims are directed to
ineligible subject matter under § 101.
3

3. The method of claim 1, further comprising detecting a
methylation status of said isolated nucleotide sequence based on
a presence or an absence of said modified base.
’213 patent
1. A method for detecting a 5-methylcytosine residue in a nucleic
acid, the method comprising:
(a) oxidizing the 5-methylcytosine residue in the nucleic acid to
generate a modified nucleic acid, wherein the oxidizing
comprises contacting the nucleic acid with TET1, TET2, TET3,
CXXC4, a catalytically active fragment of any of these, or any
combination thereof; and
(b) detecting the modified nucleic acid, wherein detection of the
modified nucleic acid is indicative of a presence of the 5methylcytosine residue in the nucleic acid.
’373 patent
1. An isolated nucleic acid from an extracellular fluid sample,
wherein a hydroxymethylated cytosine of said isolated nucleic
acid is glucosylated.
’683 patent
1. A composition comprising a mixture of a methylcytosine
dioxygenase, a DNA glucosyltransferase, and nucleic acid
comprising glucosylated 5-hydroxymethylcytosine.
II.

Legal Standard
“To survive a motion to dismiss, a complaint must contain sufficient

factual matter, accepted as true, to ‘state a claim to relief that is plausible on
its face.’” Ashcroft v. Iqbal, 556 U.S. 662, 678 (2009), quoting Bell Atl. Corp.
v. Twombly, 550 U.S. 544, 570 (2007). Two basic principles guide the
4

court’s analysis. “First, the tenet that a court must accept as true all of the
allegations contained in a complaint is inapplicable to legal conclusions.”
Iqbal, 556 U.S. at 678. “Second, only a complaint that states a plausible claim
for relief survives a motion to dismiss.” Id. at 679. A claim is facially
plausible if its factual content “allows the court to draw the reasonable
inference that the defendant is liable for the misconduct alleged.” Id. at 678.
III. Discussion
While “any new and useful process, machine, manufacture, or
composition of matter, or any new and useful improvement thereof,” may be
eligible for patent protection, 35 U.S.C. § 101, “‘laws of nature, natural
phenomena, and abstract ideas’ are not patentable,” Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 70 (2012), quoting Diamond
v. Diehr, 450 U.S. 175, 185 (1981). Courts apply a two-step framework to
evaluate subject matter eligibility:
First, we determine whether the claims at issue are directed to
one of those patent-ineligible concepts. If so, we then ask,
“[w]hat else is there in the claims before us?” To answer that
question, we consider the elements of each claim both
individually and “as an ordered combination” to determine
whether the additional elements “transform the nature of the
claim” into a patent-eligible application. We have described step
two of this analysis as a search for an “‘inventive concept’” – i.e.,
an element or combination of elements that is “sufficient to
ensure that the patent in practice amounts to significantly more
than a patent upon the [ineligible concept] itself.”
5

Alice Corp. Pty. v. CLS Bank Int’l, 573 U.S. 208, 217-218 (2014), quoting
Mayo, 566 U.S. at 72-73, 78, 79.
a. Count III
Count III asserts infringement of claim 1 of the ’818 patent, which
recites a method of exposing “a nucleic acid sequence” to “an enzyme . . . that
oxidizes at least one methylated DNA base” in “an amount effective” to
convert 5mC to 5hmC. NEB argues that this claim fails the first step of Alice
because it recites no more than a law of nature, namely, the natural reaction
that occurs when 5mC is exposed to certain enzymes. Def.’s Mem. in Supp.
of Mot. to Dismiss (Def.’s Mem.) [Dkt # 55] at 8.
The court agrees. At its core, the claim does nothing more than
replicate the natural process of “an enzyme . . . that oxidizes at least one
methylated DNA base,” ’818 patent, cl. 1, oxidizing 5mC into 5hmC. It thus
claims ineligible subject matter. See PureCircle USA Inc. v. SweeGen, Inc.,
2024 WL 20567, at *5 (Fed. Cir. Jan. 2, 2024) (“To the extent that claim 14
claims a ‘method for making Rebaudioside X comprising a step of converting
Rebaudioside D to Rebaudioside X using a UDP-glucosyltransferase,’ it
claims a natural phenomenon.

The enzyme in claim 14, UGT76G1, is

naturally found in stevia plants and naturally converts Reb D to Reb X.”).

6

Attempting to avoid this inexorable outcome, plaintiffs trumpet in
their opposition the “amount effective” language of the claim, arguing that
“[a]dministering the recited ‘effective’ amount is not a naturally occurring
phenomenon or a natural law” but instead involves a proactive treatment
step. Pls.’ Opp’n to Mot. to Dismiss (Pls.’ Opp’n) [Dkt # 69] at 18. But the
Supreme Court has expressly rejected the proposition that simply applying a
natural law in a therapeutic context renders it eligible for patenting. See
Mayo, 566 U.S. at 78; see also SAP Am., Inc. v. InvestPic, LLC, 898 F.3d
1161, 1169 (Fed. Cir. 2018) (“[L]imitation of the claims to a particular field of
information . . . does not move the claims out of the realm of abstract
ideas.”). To satisfy § 101, the claim must “do significantly more than simply
describe these natural relations.” Mayo, 566 U.S. at 78.
It follows that, if the claim does nothing more than recite a natural
process, it fails to satisfy the “inventive concept” requirement of step two.
The court accordingly will dismiss Count III of the Complaint.
b. Count II
Count II asserts infringement of claims 1 and 3 of the ’204 patent.
Claim 1 of the ’204 patent recites a “method of converting” 5mC “in an
isolated nucleotide sequence” to 5hmC by exposing the sequence to one or
more of the TETI, TET2, TET3, or CXXC4 enzymes. Claim 3 of the ’204
7

patent incorporates the method of claim 1 but adds the limitation of
“detecting” the “methylation status” of the “isolated nucleotide sequence” by
measuring the presence or absence of 5hmC.
Although claims 1 and 3 parallel the claim invalidated above, plaintiffs
assert that a different result is warranted with these claims. This is so, they
maintain, because the claimed method “creates a modified, non-naturally
occurring nucleotide sequence” which is “unnaturally rich in 5hmC and
unnaturally deficient in 5mC.” Pls.’ Opp’n at 7. The problem is this: The
claims are not directed to the allegedly new, modified nucleotide sequence
identified by plaintiffs. 3 Rather, they target the same replication of a natural
process that the court earlier found ineligible. 4 The court will accordingly
dismiss Count II for the same reasons it dismissed Count III.

3 The court does not mean to imply that claims directed to the modified

nucleotide sequence would be eligible for patenting under § 101. All the
court holds is that claims 1 and 3 are not directed to any such modified
nucleotide sequence.

4 Although the parties do not meaningfully distinguish between claims

1 and 3 in their filings, see Def’s Mem. at 8-11; Pls.’ Opp’n at 7-13, the court
further notes that the addition of the detection step recited in claim 3 adds
nothing to the underlying law of nature. It simply tells the user to detect the
results of the natural process “through whatever process the doctor or the
laboratory wishes to use.” Mayo, 566 U.S. at 79.
8

c. Count I
Count I asserts infringement of claim 1 of the ’213 patent, which recites
a “method for detecting” 5mC “in a nucleic acid” by: (a) exposing the nucleic
acid to at least one of the enzymes TET1, TET2, TET3, or CXXC4 “to
generate” 5hmC; and (b) using the presence or absence of 5hmC in the
nucleic acid to detect 5mC. Although framed in terms of detection rather
than conversion, this claim, like the ones above, is directed to the natural
oxidization of 5mC into 5hmC once it is exposed to certain enzymes. The
court accordingly will dismiss Count I for the same reasons discussed earlier.
d. Count VI
Count VI asserts infringement of claim 1 of the ’373 patent. The claim
recites “[a]n isolated nucleic acid from an extracellular fluid sample” in
which at least one 5hmC “is glucosylated.” NEB contends that this claim is
directed to ineligible subject matter because glucosylated 5hmC exists in
nature. Plaintiffs do not dispute that it exists in bacteriophages, but they
contend that this is irrelevant because the claim is limited to nucleic acid
extracted from extracellular fluid and, according to plaintiffs, 5hmC in
nucleic acid taken from extracellular fluid cannot naturally be glucosylated
prior to extraction.

9

The court reserves any ruling on this aspect of the parties’ dispute. The
issue can be resolved only with the benefit of discovery into the factual
question of whether the 5hmC in nucleic acid from extracellular fluid can in
fact be naturally glucosylated prior to extraction. 5
e. Count IV
Count IV asserts infringement of claim 1 of the ’683 patent, which
recites a “composition comprising a mixture of methylcytosine dioxygenase
[i.e., an oxidizing enzyme], a DNA glucosyltransferase, and nucleic acid
comprising glucosylated” 5hmC. Although the parties appear to agree that
the various components of the mixture exist in nature, there is a dispute of
fact as to whether the combination itself exists in nature. It is also not clear
to the court whether, if the combination does not exist in nature, there is
something in the art of mixing these components together that is sufficient
to confer patent eligibility, even though they appear to perform the same
function in the composition as they do in isolation. Thus, consistent with the
court’s decision as to claim 1 of the ’373 patent, the court reserves any ruling
on the patentability of claim 1 of the ’683 patent pending discovery.

5 And, if it cannot, whether there is something inventive in applying the

natural glucosylation process in the extracellular fluid context. NEB
persuasively asserted during the November 21, 2024 hearing that the answer
is no, but the court will reserve a ruling pending factual discovery.
10

MOTION FOR A PRELIMINARY INJUNCTION
Plaintiffs move for a preliminary injunction based on alleged
infringement of claim 3 of the ’204 patent, claim 1 of the ’683 patent, claim 1
of the ’053 patent, and claim 1 of the ’091 patent. “To obtain a preliminary
injunction, a party must establish likelihood of success on the merits,
likelihood it will suffer irreparable harm absent preliminary relief, the
balance of equities tips in its favor, and an injunction is in the public
interest.” Natera, Inc. v. NeoGenomics Lab’ys, Inc., 106 F.4th 1369, 1375
(Fed. Cir. 2024). The burden is “on the movant to show that it is likely to
succeed on the merits.” BlephEx, LLC v. Myco Indus., Inc., 24 F.4th 1391,
1398 (Fed. Cir. 2022).
Plaintiffs falter at the first step. 6 “To show likelihood of success on the
merits, a patentee must show ‘(1) it will likely prove infringement and (2) its

6 The court also entertains doubt about whether plaintiffs have shown

irreparable harm, given the availability of monetary damages and the
cautionary recent Supreme Court decision reminding district courts of the
extraordinary and rare grant of this equitable remedy. See Starbucks Corp.
v. McKinney, 144 S. Ct. 1570, 1576 (2024). And as defendant forcibly argued
at the hearing, plaintiffs have not met their burden of showing that an
injunction would serve rather than harm the public interest. Given that the
parties to the litigation are the sole suppliers of the accused products,
plaintiffs’ inability to convincingly demonstrate their capacity to scale up
production to meet the vacuum that an injunction would create in the current
market demand is a near-fatal concession on this prong of the injunctive
standard.
11

infringement claim will likely withstand challenges to the validity and
enforceability of the patents.’” Natera, 106 F.4th at 1375, quoting Purdue
Pharma L.P. v. Boehringer Ingelheim GMBH, 237 F.3d 1359, 1363 (Fed. Cir.
2001). Plaintiffs have not shown that the second element is met here. 7
“An accused infringer ‘need not make out a case of actual invalidity’ to
avoid a preliminary injunction but need only show a substantial question of
invalidity.”

Natera, 106 F.4th at 1376, quoting Amazon.com, Inc. v.

Barnesandnoble.com, Inc., 239 F.3d 1343, 1359 (Fed. Cir. 2001).

A

substantial question of invalidity is one that “the patentee cannot prove ‘lacks
substantial merit.’” Entegris, Inc. v. Pall Corp., 490 F.3d 1340, 1351 (Fed.
Cir. 2007), quoting Genentech, Inc. v. Novo Nordisk, 108 F.3d 1361, 1364
(Fed. Cir. 1997). The very fact that the court has already found claim 3 of the
’204 patent invalid and has reserved ruling on claim 1 of the ’683 patent
shows the existence of a substantial question of invalidity with respect to
these patents. As for the asserted claims of the ’053 and ’091 patents,
plaintiffs have not shown that NEB’s invalidity defenses, regardless of their

7 The court expresses no opinion as to whether plaintiffs have shown

that they will likely prove infringement.
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ultimate merits (the court expresses no opinion on this issue), lack
substantial validity. 8 The motion accordingly must be denied.
ORDER
For the forgoing reasons, the motion to dismiss is ALLOWED IN PART
and DENIED IN PART and the motion for a preliminary injunction is
DENIED. Counts I, II, and III are dismissed, and Counts IV and VI shall,
for time being, proceed to factual discovery.

SO ORDERED.
/s/ Richard G. Stearns
UNITED STATES DISTRICT JUDGE

8 Indeed, plaintiffs do not even address NEB’s argument that claim 1 of

the ’091 patent fails to enable the claimed invention or provide sufficient
written description of it. Compare Def.’s Opp’n to Pls.’ Mot. for a Prelim. Inj.
[Dkt #37] at 23-24, with Pls.’ Reply to Def. Def.’s Opp’n to Pls.’ Mot. for a
Prelim. Inj. [Dkt # 52] at 9-10.
13