7:20-cv-08255
S.D.N.Y.Dec 5, 2022UNITED STATES DISTRICT COURT
SOUTHERN DISTRICT OF NEW YORK
ALLELE BIOTECHNOLOGY AND
PHARMACEUTICALS, INC.,
Plaintiff, CLAIM CONSTRUCTION ORDER
-against- 20-CV-08255 (PMH)
REGENERON PHARMACEUTICALS, INC.,
Defendant.
PHILIP M. HALPERN, United States District Judge:
This Order sets forth the Court’s patent claim constructions pursuant to Markman v.
Westview Instruments, Inc., 517 U.S. 370 (1996). Plaintiff Allele Biotechnology and
Pharmaceuticals, Inc. (“Plaintiff” or “Allele”) alleges that Defendant Regeneron Pharmaceuticals,
Inc. (“Defendant” or “Regeneron”) infringed its patent for a “Monomeric Yellow-Green
Fluorescent Protein from Cephalochordate” (U.S. Patent No. 10,221,221) (Doc. 88-3, the “’221
Patent”). The parties ask the Court to construe four disputed terms: “isolated,” “monomeric or
dimeric LanYFP fluorescent protein,” “monomeric polypeptide,” and “non-naturally occurring.”
The Court, having thoroughly considered the parties’ briefing (Doc. 87, “Pl. Br.”; Doc. 88,
“Campbell Decl.”; Doc. 91, “Def. Br.”; Doc. 93, “Jiminez Decl.”; Doc. 96, “Pl. Reply”; Doc. 99,
“Def. Sur-Reply”), and having held a Markman hearing on November 21, 2022, herein construes
the four disputed terms.
BACKGROUND
I. The ’221 Patent
The ’221 Patent, titled “Monomeric Yellow-Green Fluorescent Protein from
Cephalochordate,” addresses the need for bright, monomeric fluorescent proteins. (See ‘211
Patent). The ’221 Patent is directed to novel green/yellow fluorescent proteins derived by protein
engineering based on an exemplary wild-type tetrameric yellow fluorescent protein from
Branchiostoma lanceolatum (“LanYFP”), a marine invertebrate of the cephalochordate
subphylum. (’221 Patent at 1-2). The’221 Patent claims a genus of “non-naturally occurring
isolated monomeric or dimeric LanYFP fluorescent proteins” and “non-naturally occurring
isolated monomeric polypeptides” with stated degrees of sequence identity (e.g., 95%) to
mNeonGreen with at least one or at least three of 21 stated mutations. (Id. at 22-23).
The specification of the ’221 patent contains five claims, set forth below, all of which
contain at least one of the disputed terms and are therefore relevant to the instant claim
construction:1
Claim 1: A non-naturally occurring isolated monomeric or dimeric LanYFP fluorescent
protein comprising a polypeptide having at least 95% sequence identity to the amino acid sequence
of SEQ ID NO: 1, wherein the protein comprises at least one mutation selected from the group
consisting of: F15I, R25Q, A45D, Q56H, F67Y, K79V, Sl00V, F115A, I118K, V140R, T141S,
M143K, L144T, D156K, T158S, S163N, Q168R, V171A, N174T, I185Y, and F192Y;
Claim 2: The non-naturally occurring LanYFP fluorescent protein of claim 1, wherein the
prоtein is a monomer;
Claim 3: An isolated non-naturally occurring monomeric polypeptide encoded by a nucleic
acid having at least 90% sequence identity to SEQ ID NO: 2 SEQ ID. No. 2, where the nucleotide
sequence encodes for a polypeptide which comprises at least one mutation selected from the group
consisting of: Il 1 SK or Nl 7 4 T, at least one mutation selected from the group consisting of:
1 “[A] patent claim is that ‘portion of the patent document that defines the scope of the
patentee's rights.’ ” Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318 , 321 (2015) (quoting
Markman v. Wеstview Instruments, Inc., 517 U.S. 370 , 372 (1996)).
V140R, L144T, D156K, T158S, Q168R, and F192Y, and at least one mutation selected from the
group consisting of: R25Q, A45D, S163N, F151, Q56H, F67Y, K79V, Sl00V, F115A, T141S,
M143K, V171A, and 1185Y;
Claim 4: The non-naturally occurring isolated monomeric or dimeric LanYFP fluorescent
protein of claim 1, wherein the protein comprises at least one mutation selected from the group
consisting of: Il 1 SK and Nl 7 4 T, at least one mutation selected from the group consisting of:
V140R, L144T, D156K, T158S, Q168R, and F192Y, and at least one mutation selected from the
group consisting of: R25Q, A45D, S163N, F151, Q56H, F67Y, K79V, Sl00V, F115A, T141S,
M143K, V171A, and I185Y; and
Claim 5: The non-naturally occurring isolated monomeric or dimeric LanYFP fluorescent
protein of any of claim 1, 3 оr 4, wherein the protein comprises a polypeptide having at least 97%
sequence identity to the amino acid sequence of SEQ ID NO: 1.
II. Relevant Prosecution History
Before it was ultimately approved, Plaintiff’s patent application was rejected by the U.S.
Patent Office (“PTO”) three separate times: on September 25, 2015, July 8, 2016, and April 11,
2017. (Doc. 88-4, “File History”).
A. September 25, 2015 Rejection
The PTO first rejected Plaintiff’s application on September 25, 2015, for failure to comply
with 35 U.S.C. §§ 101, 102, and 112. (File History at 52-64). The PTO noted that Plaintiff’s
proposed claims for “an isolated polypeptide set forth in the amino acid of SEQ ID NO:1” were
not “markedly different from the product’s naturally occurring counterpart” because the
specification did not impose any “meaningful limits . . . to set it apart from a natural product.” (Id.
at 58).
Plaintiff responded to the PTO’s initial rejection by amending the relevant claims to read
“an isolated LanYFP-derived fluorescent protein comprising a polypeptide,” which had a stated
degree of sequence identity to mNeonGreen. (Id. at 68-70). To differentiate its claimed invention
from the naturally occurring counterpart, Plaintiff further reрresented to the PTO that its
fluorescent proteins “possess [] functionally superior fluorescent properties” compared to the
naturally occurring fluorescent protein, LanYFP. (Id. at 71-72).
B. July 8, 2016 Rejection
The PTO rejected Plaintiff’s application for a second time on July 8, 2016. Despite
Plaintiff’s amendments, the patent examiner stated that “[t]he fact pattern in the application is that
the claims are directed to a product that initially appears non-naturally occurring, however is a
natural product.” (File History at 78). The examiner went on to note thаt a claimed invention which
only shares a degree of identity (e.g., 92% of sequence identity) is “simply truncating the native
structure” instead of altering it and therefore not patent-eligible. (Id. at 79).
Plaintiff responded to this second rejection by adding the phrase “non-naturally occurring”
to the relevant claims. (Id. at 88). Plaintiff further represented that the claimed invention,
monomeric or dimeric fluorescent proteins, were different from the naturally occurring
counterpart, because that protein only “occurs as a tetramer in nature.” (Id. at 91). Plaintiff further
stated that the claimed invеntion contained “significant sequence differences” from the naturally
occurring counterpart as a result of 21 stated mutations. (Id.).
C. April 11, 2017 Rejection
The PTO rejected Plaintiff’s application for a third time on April 11, 2017. The patent
examiner considered Plaintiff’s argument that the claimed invention was different than the
naturally occurring counterpart because the monomeric and dimeric embodiments of the
fluorescent proteins did not occur in nature. (File History at 102). However, the examiner stated
that Plaintiff’s arguments imposed “limitations not present in the instant claims.” (Id.). Put another
way, while it may be true that the monomeric and dimeric forms of the fluorescent protein did not
occur in nature, the language of the claims themselves did not reflect this limitation and, therefore,
the claimed invention still included a natural phenomenon in violation of 35 U.S.C. § 101.
Plaintiff responded to this third rejection by amending the claims to their current, approved
forms. (Id. at 108-109). The amended claims added the language describing the fluorescent protein
as “monomeric or dimeric” and specifying that the nucleic acid comprises at least 1 out of 21 stated
mutations. (Id.). The PTO subsequently issued the patent on March 5, 2019. (Id. at 148).
STANDARD OF REVIEW
The Court’s role at this stage in a patent proceeding is to determine, when necessary and
appropriate, the meaning of terms within a claim in order to assist the fact finder in making
subsequent and ultimate decisions as to whether a patent has in fact been infringed. The purpose
of claim construction is to define terms so that a jury may be properly instructed. See Sulzer Textil
A.G. v. Picanol N.V., 358 F.3d 1356 , 1366 (Fed. Cir. 2004) (“the trial court in a patent case must
at minimum take steps to assure that the jury understands that it is not free to consider its own
meanings for disputed claim terms and that the district court’s claim construction . . . is adopted
and applied by the jury in its deliberation of the facts”). The Court’s determination of disputed
factual issues is often necessary to the determination of the appropriate construction of a term. See
Markman v. Westview Instruments, Inc., 517 U.S. 370 , 389 (1996) (“[t]he construction of written
instruments is one of those things that judges often do and are likely to do better than jurors
unburdened by training in exegesis”). Claim construction is an issue of law properly decided by
the Court, and the analysis is substantially guided by the Federal Circuit’s decisions in Phillips v.
AWH Corp., 415 F.3d 1303 (Fеd. Cir. 2005) (en banc), and Markman v. Westview Instruments,
Inc., 52 F.3d 967 (Fed. Cir. 1995) (en banc).
Claim terms are to be given the meaning understood by a person of ordinary skill in the art
at the time of invention. Phillips, 415 F.3d at 1313 . “Properly viewed, the ‘ordinary meaning’ of a
claim term is its meaning to the ordinary artisan after reading the entire patent.” Id. at 1321. When
interpreting the meaning of claim terms, “words of a claim are generally given their ordinary and
customary meaning” as understood by “a person of ordinary skill in the art at the time of
invention, i.e., as of the effective filing date of the patent application.”2 Id. at 1312–13. Courts must
read a сlaim term “not only in the context of the particular claim in which the disputed term
appears, but in the context of the entire patent, including the specification.” Id. at 1313. “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.
The Federal Circuit has emphasized the importance of intrinsic evidence in claim
construction: the words of the claim themselves, the written description in the patent’s
specification, and, when necessary, the history of the pаtent application’s prosecution before the
PTO. Seabed Geosolutions (US) Inc. v. Magseis FF LLC, 8 F.4th 1285 , 1287 (Fed. Cir. 2021) (“we
still give primacy to intrinsic evidence, and we resort to extrinsic evidence to construe claims only
if it consistent with intrinsic evidence”); see also Phillips, 415 F.3d at 1318 (“[A] court should
discount any expert testimony that is clearly at odds with the claim construction mandated by the
claims themselves, the written description, and the prosecution history.”).
2 The parties agree that “a person of ordinary skill in the art at the time of invention” would
have a Ph.D or equivalent degree in biochemistry, сhemistry, or a related discipline and two or
more years of experience in fluorescent protein engineering. (See Doc. 87 at 9; Doc. 91 at 12).
Claim language must also be read in the context of the specification. Id. at 1315. The
specification “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. (quoting Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). The specification also acts as a
dictionary “when it defines terms by implication.” Vitronics, 90 F.3d at 1582 . However, when
relying on the specification to interpret claim terms, a court should not be confined to the
embodiments described in the specification. Phillips, 415 F.3d at 1323 . The mistake of “reading a
limitation from the written description into the claims” is “one of the cardinal sins of patent
law.” Id. at 1320 (quoting SciMed Life Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d
1337, 1340 (Fed. Cir. 2001)).
“In addition to consulting the specification, [the Federal Circuit has] held that a court
should also consider the patent’s prosecution history, if it is in evidence.” Id. at 1317. The
prosecution history “can often inform the meaning of the claim language by demonstrating how
the inventor undеrstood the invention and whether the inventor limited the invention in the course
of prosecution, making the claim scope narrower than it would otherwise be.” Id. at 1317.
However, “because the prosecution history represents an ongoing negotiation between the PTO
and the applicant, rather than the final product of that negotiation, it often lacks the clarity of the
specification and thus is less useful for claim construction purposes.” Id.
Courts may also rely on “extrinsic” evidence such as dictionaries, learned treatises, and
expert testimony, which may serve as a source of “accepted meanings of terms used in various
fields of science and technology” or provide “background on the technology at issue.” Id. at 1317– 18. However, such extrinsic evidence is “less significant than the intrinsic record in determining
the legally operative meaning of claim language,” and should only be considered within the context
of the intrinsic evidence. Id. at 1317-19.
The process of claim construction begins with the language of the claims themselves,
which the patentee selected to “particularly point out and distinctly claim the subject matter which
the applicant regards as his invention.” Phillips, at 1311-12 (quoting 35 U.S.C. § 112). Thus, “the
claims themselves provide substantial guidance as to the meaning of particular claim terms.” Id.
at 1314. In addition to the particular claim being examined, the context provided by other claims
may be helpful as well. Id.
A party seeking to limit the scope of a patent or else invalidate it altogether may do so,
inter alia, by arguing that a claim term is indefinite or that the patentee disavowed the full scope
of a term during representations made during prosecution of the patent аpplication. “[A]n inventor
may disavow claims lacking a particular feature when the specification describes ‘the present
invention’ as having that feature.” Poly-Am., L.P. v. API Indus., Inc., 839 F.3d 1131 , 1138 (Fed.
Cir. 2016). A party seeking to prove that a patentee disclaimed claim scope must be able to show
that the patentee evinced a “clear and unmistakable surrender of claim scope.” Aylus Networks,
Inc. v. Apple Inc., 856 F.3d 1353 , 1362 (Fed. Cir. 2017). The standard for finding disavowal are
“exacting” as “the specification or prosecution history [must] make clear that the invention does
not include a particular feature.” GE Lighting Sols., LLC v. AgiLight, Inc., 750 F.3d 1304 , 1309
(Fed. Cir. 2014).
Another avenue for limiting the scope of a patent, or invalidating one entirely, is through
the definiteness requirement imposed by 35 U.S.C. § 112. If a term is indefinite, then the claims
in which it appears are invalid. See Synchronoss Techs., Inc. v. Dropbox, Inc., 987 F.3d 1358 , 1368
(Fed. Cir. 2021). Definiteness is determined from the point of view of a person of ordinary skill in
the art at the time of filing and is resolved with reference to the patent’s specification and
prosecution history. Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 , 908 (2014). “The
definiteness requirement, so understood, mandates clarity, while recognizing that absolute
precision is unattainable.” Nautilus, 572 U.S. at 910 . Instead, “the certainty which the law requires
in patents is not greater than is reasonable, having regard to their subject-matter.” Id. Finally,
indefiniteness must be proven by “clear and convincing evidence” because patents are entitled to
a presumption of validity that is not readily overcome. VR Optics, LLC v. Peloton Interactive, Inc.,
345 F. Supp. 3d 394 , 398 (S.D.N.Y. 2018) (citing BASF Corp. v. Johnson Matthey Inc., 875 F.3d
1360, 1365 (Fed. Cir. 2017)). 3
ANALYSIS
I. “Isolated” (Claims 1, 3, 4, and 5)
Allele’s Proposed Construction Regeneron’s Proposed Construction
The protein is present in other than its natural The protein is separated from its natural
environment. environment.
The primary dispute here is whether the term “isolated” requires that the fluorescent protein
be affirmatively separated from the cell in which it was expressed. Regeneron argues that because
some of the examples in the specification feature the fluorescent protein separated from its cell,
the term “isolated” must require such affirmative separation. (Def. Br. at 13-15). Regeneron, in
support of its proposed construction, offered the following illustration during the Markman hearing
held by the Court:
3 This clear and convincing burden of proof standard associated with the definiteness
analysis is “one of the few instances where there is a burden of proof in Markman proceedings.”
Peter S. Menell et. al., Patent Claim Construction: A Modern Synthesis and Structured
Framework, 25 Berkeley Tech. L.J. 711, 768 (2010).
Isolated Protein Is Separated from Its
Natural Environment
is = Z aN sd
Protei a be
(x fh oe \cemen ) Separated
ee: xe
°F ¥ a
□ a ge Ps. %
Natural environment for proteins Isolated protein
is where they are made (11/21/2022 Markman Hearing, Defendant’s Presentation at 7).
Defendant further argues that the prosеcution history reflects that the examiner understood
the term “isolated” to mean separated because the examiner stated that an isolated protein “can be
made by .. . synthetic peptide synthesis or purification from the natural source.” (/d. at 16). Allele
argues that the specification is replete with embodiments that describe fluorescent proteins not
separated from the cell in which they were expressed, or purified, as part of the invention. (PI.
Reply at 4-5 (citing the °221 Patent at 8-11)). Allele further argues that statements made by the
examiner, not Allelе, during the prosecution history cannot serve as evidence to limit the term as
Regeneron proposes. (/d. at 6).
Regeneron’s proposed construction excludes, without any explanation, several
embodiments that describe fluorescent proteins not separated from the cell in which they were
expressed. (°221 Patent at 8-11). Regeneron’s proposed construction also ignores the ’221 Patent’s
10
abstract, which expressly contemplates “a host cell comprising the vector, and the use of the vector
in a method for expressing the nuclеic acid sequence.” (Id. at 2). As the Federal Circuit instructed
in Oatey Co. v. IPS Corp., “where claims can reasonably [be] interpreted to include a specific
embodiment, it is incorrect to construe the claims to exclude that embodiment, absent probative
evidence [to] the contrary.” 514 F.3d 1271 , 1277 (Fed. Cir. 2008). Here, Regeneron has not
presented probative evidence sufficient to support its proposed construction. That the patent
examiner stated that a protein could theoretically be purified is not probative to whether the term
“isolated” requires the affirmative step of separation of the fluorescent protein from the cell.
Accordingly, the Court construes “isolated” in the context used in Claims 1, 3, 4, and 5 as
meaning “the protein is present in other than its natural environment.”
II. “Monomeric or dimeric LanYFP fluorescent protein” (Claims 1, 4, and 5) and
“monomeric polypeptide” (Claim 3)
Allele’s Proposed Construction Regeneron’s Proposed Construction
Monomeric or No construction needed (plain Monomeric or dimeric green/yellow
dimeric LanYFP and ordinary meaning). fluorescent protein that has improved
fluorescent extinction coefficient, quantum yield,
protein and brightness compared to mCitrine.
Monomeric No construction needed (plain Monomeric polypeptide that has
polypeptide and ordinary meaning). improved extinction coefficient,
quantum yield, and brightness
compared to mCitrine
Plaintiff argues that these two terms should be assigned their plain and ordinary meaning.
(Pl. Br. at 17-19). Defendant does not argue that the plain and ordinary meaning of these two terms
is disputed, nor does Defendant argue that these terms are ambiguous in any way. (Def. Br. аt 20- 22). Rather, Defendant argues that the Court should read limitations into these claims because
Plaintiff disavowed the full scope of the plain and ordinary meaning. (Id.). Defendant, in support
of this argument, points to three statements Plaintiff made to the examiner over the course of a
four-year period regarding the properties of the claimed invention (Id. at 21) as follows:
“Claims 3 and 5 as a whole are directed to embodiments of fluorescent proteins
(FPs) derived/generated from a cephalochordate Branchiostoma lanceolatum
protein, which occurs as a tetramer in nature. These exemplary monomeric or
dimeric embodiments of the proteins disclosed herein were designed and generated
by structure and docking algorithms using protein engineering techniques and have
no known structural or homologs in nature and possess superior functionally
superior fluorescent properties.” (File History at 72);
“Applicants respectfully disagree with the Examiner’s assertion that the ‘claimed
invention encompasses products that have characteristics that are not markedly
different from the product's naturally occurring counterpart in its natural state’
because inherent in the recited sequence (SEQ ID NO: 2) is a structure significantly
different than the structure of the wild-type protein found in nature. Applicants
respectfully note that each of the present claims requires the polypeptide to be in a
monomeric or dimeric form, which results from the claimed sequences and is not a
form exhibited by the naturally occurring wild-type protein. The exemplary
monomers and dimers described in the instant application were specially
engineered based on the inventors’ insights, to adopt a monomeric or dimeric form
with enhanced or retained fluorescent properties. The instant application further
describes the superior properties of exemplary polypeptides of this invention,
including a brighter fluorescent signal; improved use as fluorescent tags due to the
superior properties of the smaller, monomeric or dimeric form; and superior
photostability. Each of the present claims requires a monomenc or dimeric form
which requires an engineered change to achieve that property.” (Id. at 112);
“Furthermore, the exemplary protein (mNeonGreen) is the brightest monomeric
GFP labeling fluorescent protein [] in the market today—mNeonGreen exhibits a
brightness of 274% compared to that of EGFP, whereas the commercially available
mCitrine exhibits a brightness of only 174%. One of ordinary skill in the art would
appreciate that in general, monomers are not as bright as dimers or tetramers,
because there are fewer emissive entities. While the brightness, quantum yields,
and extinction coefficients decrease form tetrameric LanYFP to dimeric dLanYFP
to monomeric mNeonGreen, the brightness per monomeric unit is the highest for
the exemplary protein mNeonGreen (Table 1). In addition, mNeonGreen exhibits a
pKa of 5.7, which as noted in the specification is ‘similar to most modern GFPs and
YFPs’ (present specification, ¶[0030]). In contrast, the tetrameric LanYFP exhibits
a pKa of 3.5. Thus, the exemplary monomeric protein mNeonGreen exhibits
markedly different physical differences from the naturally occurring tetrameric
LanYFP protein.” (Id. at 113).4
As an initial matter, where, as here, the plain and ordinary meaning of a term is undisputed,
a district court may properly decline to construe such a claim. ActiveVideo Networks, Inc. v.
Verizon Commc’ns, Inc., 694 F.3d 1312 , 1326 (Fed. Cir. 2012) (holding that a district court “did
not err in concluding that these terms have plain meanings that do not require additional
construction” and further noting that it would be erroneous to “read[] limitations” into such
undisputed claims).
Regardless, Defendant has failed to show that Plaintiff disavowed the full scope of the
plain and ordinary meaning of these terms. Each of the three statements cited by Defendants in
support of this argument were made in response to the examiner’s rejection under 35 U.S.C. § 101
for ineligible subject matter. (File History at 39, 72, 90-91, 112). These statements were made as
part of a broader discussion between the examiner and Plaintiff on whether the patent sufficiently
distinguished the claimed invention from its naturally occurring counterpart. (Id.). Plaintiff, in each
of the three statements, expressly distinguished its claimed invention from the naturally occurring
tetrameric LanYFP protein. (See supra at 11-12). Plaintiff did not claim, as Defendant suggests,
that the claimed invention has superior fluorescent properties over the prior art. (Id.). These three
statements are insufficient to show that Plaintiff disavowed any scope for the plain and ordinary
meanings of these two terms. Cadence Pharms. Inc. v. Exela PharmSci Inc., 780 F.3d 1364 , 1369
(Fed. Cir. 2015) (declining to impose a limitation on a term from statements made by the patent- holder during prosecution in response to a rejection).
4 Defendant also cites to Table 1 in the ’221 Patent, which compares Branchiostoma
lanceolatum-derived fluorescent proteins to other green and yellow fluorescent proteins, in support
of its proposed construction for these terms. (Def. Br. at 19, 21).
Accordingly, the Court declines to construe thе terms “monomeric dimeric LanYFP
fluorescent protein” and “monomeric polypeptide” because the parties agree that each term’s plain
and ordinary meaning is not in dispute, and in any event Regeneron has not satisfied its burden of
proof that the Court should impose limitations into these terms.
III. “Non-Naturally Occurring” (Claims 1-5)
Allele’s Proposed Construction Regeneron’s Proposed Construction
Different in amino acid sequence from a Indefinite.
yellow/green fluorescent protein of the
species Branchiostoma lanceolatum that is
found “as is” in naturе
Plaintiff argues that the term “non-naturally occurring” should be construed to mean
“different in amino acid sequence from a yellow/green fluorescent protein of the species
Branchiostoma lanceolatum that is found ‘as is’ in nature.” (Pl. Br. at 10-12). Defendant argues
that this term is indefinite because no person of ordinary skill in the art can be certain if a
fluorescent protein is not found in nature because new naturally occurring proteins are still being
discovered. (Def. Br. at 22-25).
Defendant, however, has failed to meet its burden to prove by clear and convincing
evidenсe that this term is indefinite. The existence of undiscovered naturally occurring fluorescent
proteins does not render the term indefinite. The parties agree that a person of ordinary skill in the
art would be able to determine whether a protein is naturally occurring by comparing that sequence
to a widely used database maintained by the National Institutes of Health known as “GenBank.”
(See Def. Br. at 23; Pl. Reply at 2). Referring to GenBank and other available databases, a person
of reasonable skill would, conversely, be able to determine within a reasonаble degree of certainty
that a fluorescent protein is not naturally occurring. This is sufficient, as “some modicum of
uncertainty” is allowed in assessing a term’s definiteness. Nautilus, 572 U.S. at 899 .
Further, the specification itself provides critical context that confirms Plaintiff’s proposed
construction of the term. For example, the specification states: “[t]he present disclosure provides
novel green/yellow fluorescent proteins derived by protein engineering based on exemplary yellow
fluorescent proteins from Branchiostoma lanceolatum (LanYFP…).” (The ’221 Patent at 61-63).
This language supports Plaintiff’s proposed construction in describing how protein engineering
techniques were used to arrive at the claimed fluorescent proteins that differ from those found “as
is” in nature.
The prosecution history is in accord with Plaintiff’s proposed construction as well. Plaintiff
amended its claims to include the term “non-naturally occurring” in response to the PTO’s
rejection of its application for not distinguishing the claimed invention from its naturally occurring
counterpart. (File History at 90-92). In addition to adding the term, Plaintiff represented that the
claimed invеntion, monomeric or dimeric fluorescent proteins, were different from the naturally
occurring counterpart, LanYFP, which “occurs as a tetramer.” (Id. at 91). Plaintiff further stated
that the claimed invention contained “significant sequence differences” from the naturally
occurring counterpart as a result of 21 stated mutations. (Id.). This amendment was made
specifically in response to the examiner asking Plaintiff to clarify how its claimed invention was
different than its naturally occurring counterpart. Through the addition of the term “non-naturally
occurring,” Plaintiff communicated to the examiner that the amino acid sequence of the claimed
invention was different from the protein that is found “as is” in nature. That is precisely the
construction Plaintiff now asks the Court to adopt.
Accordingly, the Court construes “non-naturally occurring” in the context used in claims
1-5 as meaning “different in amino acid sequence from a yellow/green fluorescent protein of the
species Branchiostoma lanceolatum that is found ‘as is’ in nature.”
CONCLUSION
For the foregoing reasons, the Court construes the disputed terms as set forth hereinabove.
SO ORDERED.
Dated: White Plains, New York
December 5, 2022
PHILIP M. HALPERN
United States District Judge