Simard, John

Patent Trials and Appeals Board

Oct 29, 2019

15584360 - (D) (P.T.A.B. Oct. 29, 2019)

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.
15/584,360 05/02/2017 John Simard 5407-0288 6594
88684 7590 10/29/2019
XBiotech, Inc.
5425 Park Central Court
Suite 111
Naples, FL 34109
EXAMINER
BURKHART, MICHAEL D
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
10/29/2019 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):
sakptomail@iplawpro.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JOHN SIMARD
____________

Appeal 2019-003759
Application 15/584,360
Technology Center 1600
____________

Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and
JOHN E. SCHNEIDER, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
The claims in this appeal are directed to a purified antibody. The
Examiner rejected the claims under 35 U.S.C. §§ 101 and 102. Pursuant to
35 U.S.C. § 134, Appellant1 appeals the Examiner’s determination that the
claims are unpatentable. We have jurisdiction for the appeal under 35
U.S.C. § 6(b).
We AFFIRM.

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 XBiotech,
Inc. Br. 3 (entered May 9, 2018).
Appeal 2019-003759
Application 15/584,360

2
STATEMENT OF THE CASE
Claims 1 and 3, the only pending claims in the application, stand
finally rejected by the Examiner as follows:
Claims 1 and 3 under pre-AIA 35 U.S.C. § 102(b) as anticipated by
Glanville et al., Proc. Nat’l. Acad. Sci., 2009, 106(48):20216–20221
(“Glanville”). Ans. 3.
Claims 1 and 3 under 35 U.S.C. § 101 because the claimed invention
is directed to a judicial exception (i.e., a law of nature, a natural
phenomenon, or an abstract idea) without significantly more.
Claim 1, the only independent claim on appeal, is reproduced below:
1. A purified antibody comprising
a variable region amino acid sequence that promotes
binding of the immunoglobulin to a target antigen,
wherein the variable region amino acid sequence is
determined by screening a phage display library comprising
variable region encoding nucleic acid sequences isolated by
PCR amplification of a cDNA library made from B
lymphocytes using human immunoglobulin variable region
leader-specific primers,
wherein the human subject was previously determined to
possess antibodies specific for the target antigen and
the variable region amino acid sequence has somatic
hypermutations in its first N-terminal 8 amino acids.

REJECTION BASED ON GRANVILLE
Claim 1 requires an antibody comprising a variable region with
somatic hypermutations in the first N-terminal 8 amino acids of the variable
region.
The Examiner found that Glanville describes a phage library encoding
human variable heavy and variable light chains. Ans. 3. The Examiner
Appeal 2019-003759
Application 15/584,360

3
found that the library was derived from peripheral blood and splenic human
lymphocytes comprising B cells. Id. The Examiner found that the “variable
regions comprise the somatic hypermutations from the sequences they were
derived from by PCR (page 20216, first column), and include such
hypermutations in the heavy chain CDRs (e.g. see Fig 2 and ¶ linking first
and second columns, page 20219), considered to be ‘the first 8 amino acids
of the variable region’” recited in claim 1. Ans. 3–4. The Examiner made
this conclusion for the following reasons:
This is because such a [variable] region is not precisely
defined in the specification, and the CDRs themselves are
considered variable regions or variable domains by Glanville et
al. Further, it is noted no such library has been prepared and
characterized in the specification, thus, the specification
provides no means for comparison as to the scope of the term
“the first 8 amino acids of the variable region”.
Ans. 4.
The issue in this rejection is whether the claimed “variable region
amino acid sequence” having “somatic hypermutations in its first N-terminal
8 amino acids” is within the CDR regions described by Granville. To
address this question, we must begin with claim interpretation.

Claim interpretation
During patent examination proceedings, claim terms are given “the
broadest reasonable meaning . . . in their ordinary usage as they would be
understood by one of ordinary skill in the art, taking into account whatever
enlightenment by way of definitions or otherwise that may be afforded by
the written description contained in the applicant’s specification.” In re
Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
Appeal 2019-003759
Application 15/584,360

4
The claimed antibody comprises “a variable region amino acid
sequence that promotes binding of the immunoglobulin to a target antigen.”
A naturally-occurring antibody has a variable region which is the part of the
antibody that binds to the antigen. The figure reproduced below shows the
antibody structure.2

As shown in the figure reproduced above, the antibody has variable
regions VL and VH (dark blue) and constant regions CH and CL (aqua).
The variable region of each heavy and light chain has four framework
regions (“FR”) depicted as blue bars and three complementarity determining
regions (“CDR”) depicted as the red bars. The inset to the figure shows that
framework region FR1 is at the amino-most terminus of each variable light
and heavy chain.
Diversity in each chain is determined by “somatic hypermutation of
variable domain nucleotides, with a concentration on CDR encoding

2 The figure is reproduced from Mirsky et al., 2014, Mol. Biol. Evol.,
32(3):806–819. The publication is provided herein and listed on the
attached PTO-892. Mirsky provides the figure as general background and is
cited as evidence of what was known prior to the date of the invention.
Appeal 2019-003759
Application 15/584,360

5
regions.” Glanville 20216 (col. 1). “As expected, most of hypermutations
accumulate in the complementarity determining regions (CDRs; see fig. 1
[same figure reproduced above]), which are directly involved in binding to
the antigen. This is partially due to the higher presence of mutational hot-
spot sequences in these regions . . . , and partially due to their plasticity.”
Mirsky 807 (col. 2). “CDRs constitute structurally flexible loops, and
therefore can accept a wider range of mutations compared with framework
regions (FRs), which have mainly a scaffolding role and must keep an
ordered-barrel structure.” Id. “The three CDR regions on each V-region
heavy and light chain show the most sequence diversity. Because of this
diversity, these regions are also called hypervariable regions.” Spec. ¶ 17.
The three CDR regions are shown in Mirsky’s figure reproduced above.

“variable region amino acid sequence has somatic hypermutations in its
first N-terminal 8 amino acids”
The Specification explains that PCR is used to make libraries of
plasmids, where PCR primers are used to amplify “cDNAs encoding heavy
and light Ig chain variable regions (V-regions) from peripheral blood
leukocytes (PBLs).” Spec. ¶ 9. The Specification teaches that “[i]n the
phage display approach, human Ig V-region genes are cloned into
bacteriophage in order to display Ab fragments on the surfaces of
bacteriophage particles.” Id. The Specification teaches that the generation
of low affinity antibodies is a major limitation of the phage display system.
Spec. ¶¶ 10, 11. The Specification states that a reason why phage display
commonly generates low affinity antibodies is that V-region primers based
on the germline sequences have been used, which “amplify the Ig sequences
Appeal 2019-003759
Application 15/584,360

6
from inside the antibody V-regions” and thus “the repertoire will be
completely devoid of antibodies with hypermutation in the 5’ end of the V-
region.” Spec. ¶ 12. The Specification states that the invention stems, inter
alia, from finding that “two amino acid substitutions in the sections of V-
regions outside the CDRs had a significant effect on an Ab’s affinity for Ag”
which led to the “startling realization that the conventional method of
amplifying V-region sequences using primers for 5’ germline end sequences
resulted in libraries that were missing many of those V-regions that have
mutations at their 5’ end.” Spec. ¶ 19 (emphasis added).
Furthermore, the Specification discloses:
Importantly, it was also realized that it was those missing V-
regions that would be expected to be included in the highest
affinity Abs. The first ten amino acids in a V-region can and
often do contain somatic hypermutations. A single amino acid
change in this region can affect antibody binding.
Spec. ¶ 19 (emphasis added).
The Specification further explains:
In the innovative approach described herein, rather than
amplifying V-regions using PCR primers for 5’ V-region
sequences, V-regions are amplified using leader sequence-
specific forward primers. Because the leader sequence is just
upstream of the V-region genes, all V-region sequences,
including those with 5’ end mutations, are amplified. The
resulting library therefore contains a more complete V-region
repertoire than those prepared by the conventional method
(which results in the loss of all V-region sequences that are
somatically hypermutated).
Spec. ¶ 20.
Based on the disclosure in the Specification and the knowledge
available at the time of the invention about antibody structure, we
understand “the sections of V-regions outside the CDRs” described in the
Appeal 2019-003759
Application 15/584,360

7
Specification at paragraph 19 to be the framework region FR1 shown in the
antibody depicted in the figure reproduced above. The “first ten amino
acids” in the V-region described in paragraph 19 are the “missing V-
regions.” These amino acids are “outside the CDRs” and therefore fall
within framework region FR1 because this region is described as the region
missing when using conventional methods (Spec. ¶ 19 as reproduced above).
This framework region is obtained by using the leader-specific primers that
are recited in the claim (“cDNA library made from B lymphocytes using
human immunoglobulin variable region leader-specific primers”). Spec. ¶
20 (reproduced above).
The claim recites that the “variable region amino acid sequence has
somatic hypermutations in its first N-terminal 8 amino acids.” Since FR1 is
at the N-terminus of the antibody chain, and the first ten amino acids of the
V region are outside the CDR region, we interpret the recited eight amino
acids to be outside the CDR regions, and in the framework region.

Product-by-process claim
Claim 1 is a “product-by-process” claim because the product – the
antibody – is claimed as a product of a process of “screening a phage display
library comprising variable region encoding nucleic acid sequences isolated
by PCR amplification of a cDNA library made from B lymphocytes using
human immunoglobulin variable region leader-specific primers.” A
product-by-process limitation defines a product in terms of how it is made.
SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1315 (Fed. Cir.
2006). “[E]ven though product-by-process claims are limited by and defined
by the process, determination of patentability is based on the product itself.”
Appeal 2019-003759
Application 15/584,360

8
In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985). The claimed structural
requirement that “the variable region amino acid sequence has somatic
hypermutations in its first N-terminal 8 amino acids” is imparted to the
claimed antibody by the process by which it is made, namely, by using
leader-specific primers to amplify the N-terminal framework region.

Discussion
The Examiner found that Granville describes antibodies with somatic
hypermutations in the CDR regions. Ans. 3–4. The Examiner did not find
that Granville describes antibodies with somatic hypermutations in the
framework region. As explained in the claim interpretation section, the
Specification expressly distinguished hypermutations in the CDR region
from those hypermutations outside the CDR region in the “first ten amino
acids in a V-region.” Spec. ¶¶ 19, 20. It would be unreasonable in light of
the Specification to interpret the first N-terminal 8 amino acids to reside in a
CDR region. Consequently, we conclude that Examiner erred in finding that
the claimed “variable region amino acid sequence has somatic
hypermutations in its first N-terminal 8 amino acids” is a CDR region. The
anticipation rejection of claims 1 and 3 based on Glanville is reversed.

REJECTION BASED ON § 101
The Examiner finally rejected claims 1 and 3 under 35 U.S.C. § 101
because the claimed invention is directed to a judicial exception to patent
eligibility. Final Act. 3; Ans. 3.
Appeal 2019-003759
Application 15/584,360

9
Principles of Law
Under 35 U.S.C. § 101, an invention is patent-eligible if it claims a
“new and useful process, machine, manufacture, or composition of matter.”
However, not every discovery is eligible for patent protection. Diamond v.
Diehr, 450 U.S. 175, 185 (1981). “Excluded from such patent protection are
laws of nature, natural phenomena, and abstract ideas.” Id. The Supreme
Court articulated a two-step analysis to determine whether a claim falls
within an excluded category of invention. Alice Corp. Pty. Ltd. v. CLS Bank
Int’l, 573 U.S. 208, 216 (2014); Mayo Collaborative Servs. v. Prometheus
Labs, Inc., 566 U.S. 66, 75–77 (2012).
In the first step, it is determined “whether the claims at issue are
directed to one of those patent-ineligible concepts.” Alice, 573 U.S. at 217.
If it is determined that the claims are directed to an ineligible concept, then
the second step of the two-part analysis is applied in which it is asked
“[w]hat else is there in the claims before us?” Id. (alteration in original).
The Court explained that this step involves
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.’
Alice, 573 U.S. at 217–18 (citing from Mayo, 566 U.S. at 75–77) (alteration
in original).
Alice, relying on the analysis in Mayo of a claim directed to a law of
nature, stated that in the second part of the analysis, “the elements of each
claim both individually and ‘as an ordered combination’” must be
considered “to determine whether the additional elements ‘transform the
Appeal 2019-003759
Application 15/584,360

10
nature of the claim’ into a patent-eligible application.” Alice, 573 U.S. at
217.
The USPTO has published revised guidance on the application of 35
U.S.C. § 101. USPTO’s January 7, 2019 Memorandum, 2019 Revised
Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50, 51–57 (2019)
(“2019 Eligibility Guidance”). This guidance provides additional direction
on how to implement the two-part analysis of Mayo and Alice.
Step 2A, Prong One, of the 2019 Guidelines, looks at the specific
limitations in the claim to determine whether the claim recites a judicial
exception to patent eligibility. In Step 2A, Prong Two, the claims are
examined to identify whether there are additional elements in the claims that
integrate the exception in a practical application, namely, is there a
“meaningful limit on the judicial exception, such that the claim is more than
a drafting effort designed to monopolize the judicial exception.” 84 Fed.
Reg. 54 (2. Prong Two).
If the claim recites a judicial exception that is not integrated into a
practical application, then as in the Mayo/Alice framework, Step 2B of the
2019 Guidelines instructs us to determine whether there is a claimed
inventive concept to ensure that the claims define an invention that is
significantly more than the ineligible concept, itself. 84 Fed. Reg. 56. In
making this determination, we must consider whether there are specific
limitations or elements recited in the claim “that are not well-understood,
routine, conventional activity in the field, which is indicative that an
inventive concept may be present” or whether the claim “simply appends
well-understood, routine, conventional activities previously known to the
industry, specified at a high level of generality, to the judicial exception,
Appeal 2019-003759
Application 15/584,360

11
indicative that an inventive concept may not be present.” 84 Fed. Reg. 56
(footnote omitted).
With these guiding principles in mind, we proceed to determine
whether the claimed subject matter in this appeal is eligible for patent
protection under 35 U.S.C. § 101. As explained in more detail below, we
conclude that the claims are directed to patent-ineligible subject matter.

Discussion
Step 2A, Prong One
In Step 2A, Prong One, of the 2019 Guidelines, the specific
limitations in the claim are examined to determine whether the claim recites
a judicial exception to patent eligibility, namely whether the claim recites an
abstract idea, law of nature, or natural phenomenon.
The Examiner found that claims 1 and 3 are directed to human
antibodies which do not differ from the same antibodies found in nature and
therefore constitute a work of nature and a natural law or phenomenon. Ans.
4. The Examiner found that the claims do not “include additional elements
that are sufficient to amount to significantly more than the judicial exception
because the recited antibodies are no different in their biological properties
than those found in the organism from which they were derived, i.e. the
recited antibodies are derived from human sequences and comprise somatic
mutations found in nature.” Id.
We agree with the Examiner’s determination.
The 2019 Guidelines do not change existing guidelines in how it is
determined whether a claim recites a law of nature or natural phenomenon.
84 Fed. Reg. 54, footnote 20.
Appeal 2019-003759
Application 15/584,360

12
The claimed antibody comprises “a variable region amino acid
sequence that promotes binding of the immunoglobulin to a target antigen.”
The variable region therefore has its natural function in binding antigen.
The variable sequences which make up the antibody are identified from a
cDNA library made from B lymphocytes from “the human subject . . .
previously determined to possess antibodies specific for the target antigen.”
The sequences are therefore naturally occurring because they are derived
from a human subject. There are no other limitations in the claim that we
have been directed to that would distinguish the antibody from one found in
nature.
Appellant contends that the rejection is incorrect because the claims
“recite a purified antibody which is a composition of matter, and 35 U.S.C.
§ 101 expressly indicates that compositions of matter are statutory subject
matter.” Br. 8. Appellants also states that “the plain language of section 101
does not mention anything about a law of nature, a natural phenomenon, or
an abstract idea, and the Office has not cited any other authority (case law)
from which the alleged ‘judicial exception’ to 35 U.S.C. 101 is derived.” Id.
Appellant’s argument is unavailing. It is true that 35 U.S.C. § 101
states that a “composition of matter” is patentable subject matter if the
conditions of the Patent Act are met. However, the Supreme Court
expressly held that there are exceptions to 35 U.S.C. § 101: “Laws of
nature, natural phenomena, and abstract ideas are not patentable.” Ass’n for
Molecular Pathology v. Myriad Genetic, Inc., 569 U.S. 576, 589 (2013).
Rather, “‘they are the basic tools of scientific and technological
work’” that lie beyond the domain of patent protection. . . . As
the Court has explained, without this exception, there would be
considerable danger that the grant of patents would “tie up” the
Appeal 2019-003759
Application 15/584,360

13
use of such tools and thereby “inhibit future innovation
premised upon them.” . . . This would be at odds with the very
point of patents, which exist to promote creation. Diamond v.
Chakrabarty, 447 U.S. 303, 309 (1980) (Products of nature are
not created, and “‘manifestations ... of nature [are] free to all
men and reserved exclusively to none’”).
Id.
The claims in Myriad included “composition claims,” such as a claim
to “[a]n isolated DNA coding for a BRCA1 polypeptide.’” Myriad, 569
U.S. at 584 (alteration in original). Reading the DNA claim as being
directed to an isolated BRCA1 gene, the Court recognized that Myriad had
“found an important and useful gene,” but concluded that “separating that
gene from its surrounding genetic material is not an act of invention.” Id. at
591. The Court found that Myriad’s claim “fell squarely within the law of
nature exception.” Id. “Myriad found the location of the BRCA1 and
BRCA2 genes, but that discovery, by itself, does not render the BRCA genes
‘new . . . composition[s] of matter,’ § 101, that are patent eligible.” Id.
Thus, Appellant’s argument that a composition of matter is statutory and
cannot be rejected under § 101 is not a correct interpretation of the law.

Step 2A, Prong Two
Prong Two of Step 2A under the 2019 Guidance asks whether there
are additional elements that integrate the exception into a practical
application. As in the Mayo/Alice framework, we must look at the claim
elements individually and “as an ordered combination” to determine whether
the additional elements integrate the recited law of nature into a practical
application.
The claims are directed to a product of nature, an antibody that has
Appeal 2019-003759
Application 15/584,360

14
been purified. Under Myriad, the claim falls within a law of nature
exception. Appellant did not identify additional elements in the claim,
which would integrate the law of nature into a practical application. We find
none, as well, because the process steps in the claim do not distinguish the
claimed antibody from one found in nature.

Step 2B
If the judicial exception is not integrated into a practical application,
then Step 2B of the 2019 Guidelines, as in the Mayo/Alice framework, asks
whether there is an inventive concept. To determine whether an
unpatentable law of nature has been transformed “into a patent-eligible
application of such law,” the Court in Mayo held that the claim as a whole
must be examined to determine whether it “also contain[s] other elements or
a combination of elements, sometimes referred to as an ‘inventive concept,’
sufficient to ensure that the patent in practice amounts to significantly more
than a patent upon the natural law itself.” See Mayo, 566 U.S. at 72–73.
Appellant did not identify an inventive concept in the claim that
would ensure that the claim is significantly more than a patent on the natural
law. Even if the step of using a leader primer is not described in the prior
art, the claim is to the product of nature, a patent-ineligible composition, and
not the method of making it.

Appeal 2019-003759
Application 15/584,360

15
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 3 102(b) Glanville 1, 3
1, 3 101 Eligibility 1, 3
Overall
Outcome
1, 3

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