immatics biotechnologies GmbH

Patent Trials and Appeals Board

Oct 27, 2020

15226098 - (D) (P.T.A.B. Oct. 27, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/226,098 08/02/2016 Toni WEINSCHENK 2912919-018007 9243
84331 7590 10/27/2020
McBee Moore & Vanik, IP, LLC
7900 Westpark Drive, Suite A100
McLean, VA 22102
EXAMINER
RAWLINGS, STEPHEN L
ART UNIT PAPER NUMBER
1643
NOTIFICATION DATE DELIVERY MODE
10/27/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing@mmviplaw.com
eofficeaction@appcoll.com
smcbee@mmviplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte TONI WEINSCHENK, OLIVER SCHOOR,
CLAUDIA TRAUTWEIN, NORBERT HILF, STEFFEN WALTER, and
HARPREET SINGH
__________

Appeal 2020-000139
Application1 15/226,098
Technology Center 1600
__________

Before RICHARD M. LEBOVITZ, RYAN H. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
pharmaceutically acceptable salt of a particular peptide sequence, and a
fusion protein, which have been rejected as directed to patent-ineligible
subject matter, and/or as being indefinite and for obviousness-type double
patenting. We have jurisdiction under 35 U.S.C. § 6(b).

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as Immatics
Biotechnologies GmbH. (Appeal Br. 1.)
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We reverse the rejection for patent-ineligible subject matter, but
affirm the obviousness-type double patenting rejection which was not
challenged on appeal.
STATEMENT OF THE CASE
Claims 1–4, 7, 9–14, and 21–27 are on appeal. Claim 1 is
representative and reads as follows:
1. A peptide consisting of the amino acid sequence of
NLDTLMTYV (SEQ ID NO: 1) in the form of
pharmaceutically acceptable salt, wherein said peptide is
produced by solid phase peptide synthesis or produced by a
yeast cell or bacterial cell expression system.
(Appeal Br. 48.)

The following grounds of rejection by the Examiner are before us on
review:
Claims 1, 3, 4, 11, and 21–26 under 35 U.S.C. § 101 as being directed
to patent-ineligible subject matter.2
Claims 1, 3, 4, 9–14, and 21–27 on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over claims 1–16
of U.S. Patent No. 9,289,478.

2 In the Final Rejection the Examiner had rejected claims 1–4, 7, 9–14, and
21–26. In the Answer, the Examiner withdrew the rejection as applied to
claims 2, 7, 9, 10, and 12–14. The Examiner also withdrew the rejection of
claims 2 and 7 under 35 U.S.C. §112(b) as being indefinite.
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DISCUSSION
I
I. Patent Eligible Subject Matter
The Dispute
The Examiner finds that claim 1 is directed to a judicial exception
“namely, a peptide or a composition comprising a peptide in which the
peptide is not markedly different from a naturally occurring peptide, such
that claimed invention is distinguished from the naturally occurring
product.” (Final Action 2–3, 7.) The Examiner states:
[T]he derivation of a salt of the peptide does not create a
marked difference between the claimed invention and the
naturally occurring peptide. This is especially true since upon
dissolution of the salt the peptide [] is present in solution as it
exists in nature. Similarly it is submitted that the acylation or
pegylation of the peptide or its linkage to a solid resin does not
substantially alter its structure by creating a marked and
significant difference between it and its naturally occurring
counterpart.
(Id. at 3.) The Examiner indicates that formation of a salt is analogous to
putting a scarf around a snowman, in that the addition of the scarf does not
change the structure of the underlying snowman. (Id. at 9–10.) The
Examiner indicates that just as the snowman structure is the same when the
scarf is removed, the removal of the salt group from the peptide when placed
in solution results in a peptide is “essentially the same as it was before the
salt was formed,” i.e., “its structure has not been markedly altered.” (Id at
10; Ans. 7.)
Appellant argues that “the proper analysis for step 2A is to look at
what is claimed and determine whether it has an identical natural
counterpart. If an identical counterpart to what is claimed does not exist,
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that is the end of the analysis.” (Appeal Br. 14. (emphasis omitted).)
Appellant points out that “there is no naturally occurring peptide of SEQ ID
No: 1 either in free form or in the form of a pharmaceutically acceptable
salt” and, therefore, “it is impossible for the claims to be ‘directed’ to a
judicial exception.” (Id. at 16.)
Appellant argues that it is an improper analysis under § 101 to
“parse[] [the claim] into i) the 9-amino acid and ii) a salt.” (Id. at 17.)
Appellant explains that
what occurs in nature is either a whole 816 amino acid 3-D
NLGN4X protein, or the peptide complexed with other
molecules (where it is not, at anytime, in the form of a
pharmaceutically acceptable salt).
(Id. at 16.) Undergirding Appellant’s argument is the testimony of
Dr. Lawrence Stern. (Id. at 17–24 (citing Stern Declaration3).)
Appellant further explains, with support from the testimony of
Dr. Stern, that the claimed peptide salt is markedly different from how the
amino acid sequence of SEQ ID NO: 1 is found in nature, i.e., “either within
a spiral domain of the NLGN4X protein or associated with an MHC-I
molecule.” (Id. at 25–29.) In addition, Appellant explains, with support
from the testimony of Dr. Stern, that even assuming a free peptide of SEQ
ID NO: 1 exists in nature, the claimed pharmaceutically acceptable salt is
structurally and functionally different from such a free peptide. (Id. at 29–
30.)
Appellant argues that the Examiner “offered no evidence rebutting
any of Dr. Stern’s [factual] statements” and factual “literature-based

3 Declaration of Dr. Lawrence Stern, dated May 16, 2018 (“Stern
Declaration”).
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evidence” in support thereof, and instead maintained the rejection of
ineligibility only on an analogy to dressing a snowman. (Id. at 32–34, 36–
38.)

Analysis
35 U.S.C. § 101 defines patent-eligible subject matter. An invention
is patent-eligible if it claims a “new and useful process, machine,
manufacture, or composition of matter.” 35 U.S.C. § 101. The Supreme
Court, however, has carved out exceptions to what would otherwise appear
to be within the literal scope of § 101, e.g., “[l]aws of nature [and] natural
phenomena” such as products of nature that are considered “buildin[g]
block[s] of human ingenuity.” Alice Corp. v. CLS Bank Int’l, 573 U.S. 208,
216 (2014) (citing Ass’n for Molecular Pathology v. Myriad, 569 U.S. 576
(2013) and Mayo Collaborative Servs. v. Prometheus Labs, Inc., 566 U.S.
66, 89 (2012)). “[T]he ‘manifestations of laws of nature’ are ‘part of the
storehouse of knowledge,’ ‘free to all men and reserved exclusively to
none.’” Manual of Patent Examiner Procedure (“MPEP”) § 2106.04(b)
(quoting Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130
(1948)). “When a law of nature or natural phenomenon is claimed as a
physical product, the courts have often referred to the exception as a
‘product of nature.’” MPEP § 2106.04(b)(II).
The Supreme Court has established a two-step framework for
“distinguishing patents that claim laws of nature, natural phenomena, and
abstract ideas from those that claim patent-eligible applications of those
concepts.” Alice, 573 U.S. at 216. “First, we determine whether the claims
at issue are directed to” a patent-ineligible concept. Id. If so, “we consider
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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.” Id. (quoting Mayo,
566 U.S. at 78–79).
The United States Patent and Trademark Office (“PTO”) issued the
2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”),
indicating how the PTO would analyze patent eligibility under the Supreme
Court’s two-step framework. 84 Fed. Reg. 50–57 (January 7, 2019).4
Under the Guidance, in determining what concept a claim is “directed
to,” we first look to whether the claim recites any judicial exceptions,
including laws of nature, natural phenomena, and/or abstract ideas.
Guidance, 84 Fed. Reg. at 53–54 (“Step 2A, Prong One”). If it does, then
we look to whether the claim recites additional elements that integrate the
recited judicial exception into a practical application. Id. at 54–55 (citing
MPEP § 2106.05(a)–(c), (e)–(h)) (“Step 2A, Prong Two”).
Only if a claim (1) recites a judicial exception and (2) does not
integrate that exception into a practical application, i.e., it is found to be
“directed to” a judicial exception, do we then look to whether the claim
contains an “‘inventive concept’ sufficient to ‘transform’” the claimed
judicial exception into a patent-eligible application of the judicial exception.

4 “All USPTO personnel are, as a matter of internal agency management,
expected to follow the guidance.” Id. at 51; see also USPTO, October 2019
Update: Subject Matter Eligibility 1 (the “October 2019 Update”) (available
at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_
update.pdf).
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Guidance, 84 Fed. Reg. at 56; see also Alice, 573 U.S. at 221 (quoting Mayo,
566 U.S. at 82).
Claims alleged to be patent-ineligible because they recite products of
nature are properly analyzed under the framework of the Guidance. See
Guidance, 84 Fed. Reg. at 54 n.20 (“This notice does not change the type of
claim limitations that are considered to recite a law of nature or natural
phenomenon. For more information about laws of nature and natural
phenomena, including products of nature, see MPEP 2106.04(b) and (c).”).
Applying the Guidance and binding legal precedent, we disagree with
the Examiner’s conclusion that the claims are directed to patent-ineligible
subject matter. We address independent claim 1 as the representative claim
for our analysis. There is no dispute that claim 1, which recites a peptide in
the form of a pharmaceutically acceptable salt, is a composition and, thus,
falls squarely within the “composition of matter” statutory category.
Consequently, we proceed to the next steps of the analysis.
STEP 2A, Prong One:
In Step 2A, Prong One of the Guidance, we evaluate whether claim 1
recites a judicial exception, i.e., whether it sets forth or describes a product
of nature in accordance with the guidance in MPEP § 2106.04 (b) and (c).
Guidance, 84 Fed. Reg. at 54; October 2019 Update.
a. Product of Nature Analysis
Claim 1 requires a peptide “consisting of the amino acid sequence of
NLDTLMTYV (SEQ ID NO: 1)” where that peptide is in the form of a
pharmaceutically acceptable salt. The claim includes the recitation of a
peptide sequence that is undisputedly found in nature as part of a protein
with a larger sequence. As Appellant’s Specification explains, SEQ ID NO:
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1 is a peptide sequence from the protein NLGN4X which is highly
overexpressed in glioblastomas compared to normal brain and other vital
tissues. (Subst. Spec. 27 (Table 1), 49.) However, as Appellant points out,
the claim does not recite a free peptide, but rather a pharmaceutically
acceptable salt of that peptide. Thus, the amino acid sequence of the peptide
salt cannot be anything other than SEQ ID NO: 1, but the peptide having that
sequence must be in ionic combination with another ion to form a
pharmaceutically acceptable salt. The claimed salt is a structurally different
chemical composition from a free peptide, as even the Examiner
acknowledges (Ans. 6 (that the peptide is a salt “simply means one or more
of the amino acid residues of which the peptide is composed has been
ionized and has formed an ionic bond with whatever cation (e.g., Na+) or
anion (e.g., C1-) might be present.”). (See Stern Declaration ¶ 20 (“Salts are
formed when a compound that is ionized in solution forms a strong ionic
interaction with an oppositely charged counterion, leading to neutralization
of the charges . . . .”), id. ¶¶ 23–24 (“[P]eptides of any length . . . will
therefore have a one free amino group (NH2) referred to as the amino
terminus or N-terminus and one free carboxyl group (COOH) referred to as
the carboxyl terminus or C-terminus . . . . [T]here can also be ionizable
groups in the side chains (‘R’) of the amino acid residues within the
peptide.”).)
Appellant’s expert explained, with reference to numerous articles, that
a peptide with the amino acid sequence of SEQ ID NO: 1 would not exist in
the body as a salt. (Stern Declaration ¶¶ 32–33, 35.) Dr. Stern explained
that peptide fragments, such as ones having amino acid sequence SEQ ID
NO: 1, that arise when proteins are degraded are themselves degraded within
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a few seconds if not associated with other proteins involved in degradation,
ER transport and loading of the peptide onto MHC-1 molecules. (Stern
Declaration ¶ 32.) Dr. Stern notes that “[i]n the absence of peptide binding,
neither the peptide nor the MHC molecule by itself is stable, or persists” in
nature. (Id. ¶ 33.)
Dr. Stern further explains that even if the free peptide existed in the
cell, “there is no acid-base reaction that could occur in the cytoplasm or ER
of a cell . . . that would result in formation of a peptide salt.” (Id. ¶ 35.)
This is because “[t]he formation of salts requires specific combinations of
acids or bases in specific concentrations, at a defined ratio (stoichiometry),
so that there is a set number of moles of acid and moles of base in a
controlled environment[, and] [t]he cytoplasm of a cell is not such an
environment.” (Id.) Dr. Stern notes that the cytoplasm “would not contain
either the peptides or the acid or base counterpart in sufficient quantities in
sufficient proximity to each other to form a peptide salt.” (Id.) Furthermore,
Dr. Stern explains that “[e]ven if all the water in cell were removed, specific
salts would not form, because of the highly complex mixtures of anions and
cations present.” (Id.)
The Examiner has not provided any evidence in contravention of the
foregoing testimony by Dr. Stern. Rather, the Examiner asserts that peptide
in salt form, nevertheless, will consist of the amino acid SEQ ID NO: 1 and
thus it is not “significantly changed.” (Ans. 5, 7.) The Examiner also
asserts, without evidentiary support, that because of the presence of certain
amino acids in the sequence “it is conceivable that the salt of the peptide
may have formed by association with two cations and one anion.” (Ans. 6.)
The Examiner states:
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naturally occurring peptides such as the peptide of SEQ ID
NO: 1 are expected to exist at physiological pH (pH = 7.4) in
the body of human in or on the surface of a cell expressing
NLGN4X in the context of an HLA-A2 class I complex . . . .
Furthermore, as example, it is known that most of the Na+ in the
body is present in the blood (plasma) and the interstitial,
extracellular fluid, which surrounds the cells[ ], where it might
freely associate with the negatively charged carboxyl terminus
and/or the negatively charged aspartic acid residue of the
peptide lying the in the cleft of the HLA complex to form a salt
thereof.
(Ans. 9–10 (footnote omitted).)
Also, relying on general principles of chemistry, the Examiner posits
that because the peptide was “found to be present on the surface of human
glioblastoma cells” and “is bound in the peptide-binding cleft of the HLA
class I complex” and is ionized at physiological pH, “and fully capable of
forming a salt with any counterions,” and that “[i]t is fully expected that
counterions such as Na+ are in fact present,” that “it is expected that the
naturally occurring peptide of SEQ ID NO: 1 exists as a salt.” (Id. at 16.)
The Examiner’s assertion that, in general, the peptide fragment of
protein degraded by a proteasome will naturally form a salt because there are
counterions such as sodium and chloride around in the cell lacks any
evidentiary foundation. And, it is contradicted by the testimony of Dr. Stern
that salt formation requires specific combinations of acids or bases in
specific concentrations, at a defined ratio (stoichiometry), so that there is a
set number of moles of acid and moles of base in a controlled environment.
The Examiner did not establish that that the cytosol, the ER and the MHC in
vivo are such a controlled environment with respect to peptide fragments of
protein degraded by a proteasome.
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In addition, the Examiner’s position that the free peptide is extant in
the first place for long enough to form a salt is contradicted by Dr. Stern’s
testimony that any free peptide of the collagen protein degraded by a
proteasome would be rapidly degraded if it is not associated with certain
other proteins in the cytosol or in transport to the endoplasmic reticulum or
when bound in the MHC.
While an amino acid sequence consisting of SEQ ID NO: 1 is
unquestionably identical to a peptide sequence found in NLGN4X, which
Appellant does not dispute, we conclude that the preponderance of the
evidence favors finding that the claimed pharmaceutically acceptable salt of
the peptide consisting of the amino acid sequence of SEQ ID NO: 1 is not a
compound that occurs in nature.
Furthermore, we disagree with the Examiner’s conclusion that the
claimed invention is not markedly different from a naturally occurring
peptide consisting of an amino acid sequence of SEQ ID NO: 1.5 The
Examiner’s analysis does not properly address the claimed structure, as
discussed above. The markedly different characteristics analysis is not
applied to the component parts of the claimed salt, but to the compound as a
whole. See, e.g., MPEP § 2106.04(c)(I)(A).
As the MPEP notes,
The courts have emphasized that to show a marked difference, a
characteristic must be changed as compared to nature, and
cannot be an inherent or innate characteristic of the naturally

5 We note, but do not find it necessary to respond to, Appellant’s arguments
concerning any alleged misapplication of law in the MPEP. (Appeal Br. 10.)
We need not address this argument because we conclude that the Examiner
erred in evaluating the claimed invention as a whole.
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occurring counterpart or an incidental change in a characteristic
of the naturally occurring counterpart. Myriad, 569 U.S. at
580[ ]. Thus, in order to be markedly different, applicant must
have caused the claimed product to possess at least one
characteristic that is different from that of the counterpart.
Id. § 2106.04(c)(II)(C). As the MPEP further explains, the “[m]arkedly
different characteristics can be expressed as the product’s structure, function,
and/or other properties, and are evaluated based on what is recited in the
claim on a case-by-case basis.” Id. § 2106.04(c)(II).
The question for consideration here is whether the structure claimed is
different from the peptide sequence as it is found in nature. As just
discussed, the evidence of record favors Appellant’s position that the
claimed peptide does not exist in nature as a free peptide.
Furthermore, it cannot be said that the pharmaceutically acceptable
salt of amino acid peptide of SEQ ID NO: 1 is merely an isolated component
of a larger structure known to be present in nature, similar to DNA isolated
from the human genome. Cf. Myriad, 569 U.S. at 593 (“Nor are Myriad’s
claims saved by the fact that isolating DNA from the human genome severs
chemical bonds and thereby creates a nonnaturally occurring molecule.”);
see also Roche Molecular Sys., Inc. v. CEPHEID, 905 F.3d 1363 (Fed. Cir.
2018) (finding similar to the claimed DNA at issue in Myriad, that the
claimed primers were necessarily present in the natural genome of Mtb). In
Myriad, the Supreme Court determined that naturally occurring, but isolated,
DNA fell within the product of nature exception because “Myriad’s
claims . . . do [not] rely in any way on the chemical changes that result from
the isolation of a particular section of DNA.” Myriad, 569 U.S. at 593. The
Court in Myriad, however, also noted that “creation of a cDNA sequence
from mRNA results in an exons-only molecule that is not naturally
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occurring” and determined that such a chemical construct is patent-eligible.
Id. at 594. Here, the markedly different characteristic for the claimed
invention is not merely due to the breaking of chemical bonds, but it is rather
based on chemical differences between the peptide as it is found in nature in
NLGN4X, and the claimed pharmaceutically acceptable salt of the peptide
of SEQ ID NO: 1 that is in ionic interaction with an oppositely charged
counterion. This structural difference is not an inherent or innate
characteristic of the naturally occurring peptide as it is found in nature or an
incidental change as Appellant’s expert testimony and underlying supporting
evidence establishes.
We conclude that, like the cDNA in Myriad, the pharmaceutically
acceptable salt of the peptide consisting of amino acid SEQ ID NO: 1 is
markedly different from the naturally occurring peptide sequence of amino
acid SEQ ID NO: 1 found in NLGN4X.6

6 In addition to this structural difference, Dr. Stern contends that the free
peptide would be poorly soluble in aqueous solution (Stern Declaration ¶ 38)
whereas “[s]alts of hydrophobic peptides have been shown improve their
solubility in aqueous solutions, just as salts of other compounds improve
their solubility” (Id. ¶ 41). He also contends that “[p]eptides are not very
stable in free form, without modifications” (Id. ¶ 42) and that the peptide
claimed may be deaminated, oxidized, or may undergo hydrolysis in
aqueous solution (Id. ¶ 43), whereas “[f]ormation of peptide salts stabilizes
the peptides from physical degradation, discussed above, to some extent”
(Id. ¶ 46). In light of our conclusion regarding the marked structural
difference, we need not address Appellant’s additional argument and
testimony of Dr. Stern that the physical properties of the pharmaceutically
acceptable salt of the claimed peptide fragment is markedly different than a
free peptide fragment if it existed in nature.
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Accordingly, under Guidance Step 2A, Prong 1, we conclude that the
composition of claim 1 does not recite a product of nature, and thus is not
directed to a patent ineligible judicial exception. Our analysis of the issue
need not proceed further.
In light of the foregoing, we do not affirm the Examiner’s rejection of
claims 1, 3, 4, 11, and 21–26 under 35 U.S.C. § 101 as being directed to
patent-ineligible subject matter.
III. Non-statutory double patenting
Appellant did not argue the substance of this rejection nor has it
indicated that a terminal disclaimer was filed. Thus, we summarily affirm
the Examiner’s rejection based on the judicially created doctrine of
obviousness-type double patenting for the reasons advanced by the
Examiner in the Final Rejection. See MPEP § 1205.02 (“If a ground of
rejection stated by the examiner is not addressed in the appellant’s brief,
appellant has waived any challenge to that ground of rejection and the Board
may summarily sustain it, unless the examiner subsequently withdrew the
rejection in the examiner’s answer.”).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3, 4, 11,
21–26
101 Eligibility 1, 3, 4, 11,
21–26
1, 3, 4, 9–
14, 21–27
Nonstatutory
Double Patenting
1, 3, 4, 9–
14, 21–27

Overall
Outcome
1, 3, 4, 9–
14, 21–27

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED