Ex Parte Brimnes et al

Patent Trial and Appeal Board

Dec 15, 2017

13879509 (P.T.A.B. Dec. 15, 2017)

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.
13/879,509 04/15/2013 Jens Brimnes A88450 1060US (0007.8) 3766
26158 7590 12/19/2017
WOMBLE BOND DICKINSON (US) LLP
ATTN: IP DOCKETING
P.O. BOX 7037
ATLANTA, GA 30357-0037
EXAMINER
ROONEY, NORA MAUREEN
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
12/19/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JENS BRIMNES and KAARE LUND
Appeal 2017-010975
Application 13/879,5091
Technology Center 1600
Before FRANCISCO C. PRATS, RYAN H. FLAX, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to methods of
suppressing type 1 hypersensitivity immune responses to allergens. The
Examiner rejected the claims for failing to comply with the written
description requirement.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants state that the “real party in interest in this appeal is ALK-Abello
A/S, the assignee of the above referenced patent application.” Br. 1.
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Application 13/879,509
STATEMENT OF THE CASE
Appellants’ invention “relates to the treatment, including prophylactic
treatment, of a hypersensitivity immune response in an individual with an
antigen unrelated to the allergen triggering a hypersensitivity immune
response in the individual. That is to say that the present invention also
relates to bystander suppression of a hypersensitivity immune response.”
Spec. 2.
Appellants’ Specification explains that “[t]he term ‘bystander
suppression’ is generally meant to encompass the ability to suppress an
immune reaction in an individual towards one antigen (A) by treatment of
the individual with another unrelated antigen (B).” Id. at 9.
The Specification discloses that the hypersensitivity-suppressing
unrelated secondary antigen may be obtained from the same source material
as the hypersensitivity-causing allergen:
[T]he present inventors have found that the unrelated antigen
might be selected among antigens present in a source material
also comprising the antigen triggering a hypersensitivity
immune response in an individual, such as be selected among
antigens present in pollen, animal dander or a dietary product
comprising an antigen (i.e. allergen) capable of triggering a
hypersensitivity immune response in an individual.
Id. at 3.
The Specification discloses that, after identifying the source material
that contains the hypersensitivity-causing allergen, the “source material may
then be subjected to various extraction protocols, preferably where focus is
on isolating a water-soluble unrelated antigen [that suppresses the
hypersensitivity reaction to the allergen]. For example, the unrelated antigen
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may be extracted from the source material comprising mainly aqueous
extraction solvents.” Id. at 18.
After extraction is performed on the source material, “[vjarious
fractions from the extraction procedure may then be subjected to methods
suitable for detecting the unrelated antigen. Crossed radioimmuno-
electrophoresis (CRIE) is a suitable method for this purpose.” Id.
The Specification describes the crossed radioimmuno-electrophoresis
(CRIE) process as follows:
In brief, a suitable method for providing an unrelated antigen is
to provide water-soluble protein extracts of a source material,
e.g. pollen, which are then separated by electrophoresis,
followed by another electrophoresis through a gel containing
IgG antibodies raised against the water-soluble protein extract
in question. IgG antibodies can be raised by immunising
rabbits. The resulting antibody: antigen complexes (Ab:Ag
complexes) can then be visualized by Coomasie blue staining or
be incubated with sera from pollen sensitized individuals
followed by anti human IgE antibodies, in order to visualize the
allergens of the pollen extract. The antigens that are not bound
by IgE antibodies from patient’s sera are considered to be
candidates to an unrelated [hypersensitivity-suppressing]
antigen.
Id. at 18—19 (emphasis added).
Example 7 in the Specification describes procedures in which antigens
unrelated to hypersensitivity-causing allergens were isolated from “pollen
allergens of Phleum Pratense (Phi p [timothy grass]) or of mite
(Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae
(Der f) allergens (mite bodies and culture medium).” Id. at 58.
Example 7’s extraction procedure is described as follows:
1 g of pollen (Phi p) or 1 g of mite bodies + mite culture (Der p
or Der f) were suspended in 10 ml of aqueous solution of
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0.125 M NH4HCO3 and 15 mM NaN3 and left overnight at
+5°C under stirring. The suspension was centrifuged at 27.000
g for 30 minutes at +5°C followed by filtration, if necessary.
The precipitate was discarded. The extract was dialysed 3 x
4hrs against 5 mM NH4HCO3 followed by 4hrs against purified
water. The volume of dialysis water was 20-50 times the
volume in the dialysis bag. The dialysed extract is then
lyophilised at -80°C and stored in an air tight container at
-20°C.
Id.
After performing crossed radioimmuno-electrophoresis on the pollen
and mite extracts, a number of antigens did not react to IgE from sera from
allergic patients, and were therefore considered candidates for suppressing
hypersensitivity. See id. at 59 (In the Phi p pollen experiment, “the
antigen[s] numbered 2, 5, 7, 12, 14, 16, 17 and 31 are . . . candidates of an
unrelated [hypersensitivity-suppressing] antigen of the invention.”); id. (In
the Der p (mite) experiment “the antigen[s] numbered 1, 3, 7, 8, and 9 . . .
are candidates of an unrelated antigen of the invention” and in the Der f
(mite) experiment “the antigen[s] numbered 2, 3, 4, 5, 10 and 17 ... are
candidates of an unrelated antigen of the invention.”).
In Examples 1—5, the Specification discloses that sublingual
administration of an aqueous extract of pollen from the grass Phleum
pretense (timothy grass) inhibits symptoms of hypersensitivity reactions to
chicken ovalbumin (OVA) in a mouse model. Id. at 49—56.
In Example 6, the Specification discloses that the sublingual
administration of a single antigen, “Phi p 5,” isolated from pollen of the
grass Phleum pretense (timothy grass), inhibits symptoms of a
hypersensitivity reaction to chicken ovalbumin in a mouse model. Id. at 57—
58.
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Application 13/879,509
Claim 31 is representative of the appealed subject matter and reads as
follows:
31. A method for suppressing a type 1 hypersensitivity
response against a protein allergen in an individual, where the
type 1 hypersensitivity response is triggered by exposure of the
individual to a protein allergen of an environmental or dietary
source material, wherein said source material, in addition to the
protein allergen, comprises at least one non-allergenic protein
antigen,
the method comprising inducing by sublingual
immunotherapy (SLIT) with said at least one non-allergenic
protein antigen a non-allergenic immune response in said
individual against said at least one non-allergenic protein
antigen, said immune response being effective to suppress said
type 1 hypersensitivity response against the protein allergen in
the individual upon exposure to said environmental or dietary
source material, where said SLIT does not comprise
administration of said protein allergen
wherein said at least one non-allergenic protein antigen is
obtainable from said environmental or dietary source material
by a method comprising co-extraction of said at least one non-
allergenic protein antigen together with the protein allergen in
an aqueous solution at pH 6—8 for a period not exceeding 30
minutes and subsequent separation from the protein allergen by
crossed radio immuno-electrophoresis.
Br. 13-14.
The sole rejection before us for review is the Examiner’s rejection of
claims 27, 31, 32, and 34-44 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement. Ans. 3—11.
WRITTEN DESCRIPTION
The Examiner’s Prima Facie Case
In rejecting claims 27, 31, 32, and 34-44, the Examiner contends that,
although Appellants’ Specification demonstrates possession of the methods
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described in Examples 1—6, Appellants are not in possession of the claimed
methods, which are not the same, and, in particular, the genus of non-
allergenic hypersensitivity-suppressing antigens recited in the claims. Ans.
3-5.
The Examiner concludes that, as source material for the
hypersensitivity-suppressing antigen administered in the claimed processes,
the claims “encompass all pollen, environmental or dietary source materials
which comprise an allergen.” Id. at 5. The Examiner finds, however, that
[t]he specification has not adequately described the genus
of non-allergenic protein antigens which may be obtainable
from any pollen, environmental or dietary source material by
co-extraction of said at least one non-allergenic protein antigen
together with the protein allergen in an aqueous solution at pH
6—8 for a period not exceeding 30 minutes and subsequent
separation from the protein allergen by crossed radio immune-
electrophoresis.
Id.; see also id. at 6 (“The specification has not adequately described the
genus of antigens, allergens and source materials recited within the
claims.”).
The Examiner finds, moreover, that the “determination of
allergenicity is not predictable and the specification has not disclosed a
correlation between the structure of the source material and the function of
having at least one non-allergenic protein which can be co-extracted with a
protein allergen of the source material” in the manner recited in the rejected
claims. Id. at 6.
In particular, the Examiner contends, the Specification
has not described any single non-allergenic protein of Phleum
pratense pollen, much less the genus of non-allergenic proteins
of Phleum pretense pollen which may be co-extracted with the
any of the genus of allergens encompassed by the claims. In
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fact, it is not even established which of Phi p 1, Phi p 2, Phi p 4,
Phi p 5, Phi p 6, Phi p 7, Phi p 11, Phi p 12 or Phi p 13 can be
extracted as recited in the claims, much less the genus of non-
allergenic proteins which may be co-extracted with the
allergens that can be extracted by the recited method.
Id.; see also id. at 9-11 (determining that even if the Specification provides
for identification of claim-encompassed species through experimentation,
that is insufficient to establish descriptive support).
As evidence of the unpredictability inherent in determining
allergenicity, the Examiner cites Obersteiner2 (allergenicity of pollen
significantly affected by associated microbiome), Petersen3 (timothy pollen
contains numerous antigenic proteins lacking IgE activity), and Oliveira4
(bystander antigen can amplify rather than suppress hypersensitivity). Id. at
6-9.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
2 Andrea Obersteiner et al., Pollen-Associated Microbiome Correlates
with Pollution Parameters and the Allergenicity of Pollen, 11 PLoS ONE
e0149545 doi:10.1371/joumal.pone.0149545 (2016).
3 A. Petersen et al., Epitope mapping of allergens and antigens of timothy
pollen extract, 2 Appl. Theor. Electrophor. 129—133 (1991) (abstract
only).
4 C.R. Oliveira, Bystander Effect in Synergy to Anergy in Oral Tolerance of
Blomia Tropical is/Ovalbumin Murine Co-Immunization Model, 25 J. Clin.
Immunol. 153-161 (2005).
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We select claim 31 as representative of the claims subject to this
ground of rejection. See 37 C.F.R. § 41.37(c)(l)(iv).
Appellants do not persuade us that a preponderance of the evidence
fails to support the Examiner’s prima facie case of lack of written
description as to claim 31.
“The written description requirement. . . ensures that when a patent
claims a genus by its function or result, the specification recites sufficient
materials to accomplish that function - a problem that is particularly acute in
the biological arts.” AriadPharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336,
1352—53 (Fed. Cir. 2010) (en banc). Thus, a “sufficient description of a
genus . . . requires the disclosure of either a representative number of species
falling within the scope of the genus or structural features common to the
members of the genus so that one of skill in the art can ‘visualize or
recognize’ the members of the genus.” Id. at 1350 (quoting Regents of the
University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568—69 (Fed.
Cir. 1997)). Accordingly, “merely drawing a fence around the outer limits
of a purported genus is not an adequate substitute for describing a variety of
materials constituting the genus and showing that one has invented a genus
and not just a species.” Id. Ultimately, the “test for sufficiency is whether
the disclosure of the application relied upon reasonably conveys to those
skilled in the art that the inventor had possession of the claimed subject
matter as of the filing date.” Id. at 1351.
For example, similar to the claims under consideration herein,
University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916 (Fed. Cir.
2004) involved a claim (claim 6) that recited a method of selectively
inhibiting a specific enzyme involved in inflammation by administering a
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non-steroidal compound (NSAID), the claim reciting a specific procedure
for identifying an NSAID capable of the selective inhibition required by the
claim. Id. at 917—18. Although the claim specified a broad category of
drugs (NSAIDS) that an ordinary artisan could readily envision testing
according to the claim-recited procedure, the court found, nonetheless, that
the claims lacked written description, because the patentees failed to provide
any specific examples of compounds falling within the genus of NSAIDS
having the claim-recited property, and therefore failed to show possession of
the claimed genus of compounds. See id. at 927.
In the present case, representative claim 31 recites a process of
suppressing, in an individual, a type 1 hypersensitivity response against any
environmental or dietary protein allergen. Br. 13. Appellants do not
persuade us, therefore (see Br. 5), that the claims do not recite treating an
individual having an undesired health condition (allergy). Moreover,
because the treated condition is a type 1 hypersensitivity response against
any environmental or dietary protein allergen, the genus of treated condition
is broad.
Representative claim 31 recites treating the condition by sublingually
administering any non-allergenic protein antigen obtainable from the
environmental or dietary source material which also contains the
hypersensitivity-inducing allergen. Id. at 14. The hypersensitivity­
suppressing protein antigen may be any protein antigen obtainable by co­
extracting the non-allergenic protein antigen together with the protein
allergen in an aqueous solution at pH 6—8 for no more than 30 minutes, and
subsequently separating the protein allergen from the hypersensitivity­
suppressing antigen by crossed radio immuno-electrophoresis. Id. Thus,
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contrary to Appellants’ arguments (Br. 5—6), the claims recite a broad genus
of starting materials from which the hypersensitivity-suppressing antigen
may be obtained: any allergen-containing environmental or dietary
substance.
Similar to the situation in University of Rochester, despite the breadth
of the disorders treated and treating compounds recited in claim 31,
Appellants do not identify, nor do we discern, any working examples of any
hypersensitivity-suppressing antigen obtained by the process recited in the
claim. Although Appellants contend that the examples in the Specification
provide an adequate description of the claimed hypersensitivity-suppressing
antigens (Br. 7—11), Examples 1—5 describe ameliorating in a mouse model a
hypersensitivity response to chicken ovalbumin by administering a different
source material, an aqueous extract of Phleum pretense (timothy grass)
pollen, as noted above. See Spec. 49-56. Examples 1—5, therefore, do not
describe treating a hypersensitivity response to an allergen by administering
a hypersensitivity-suppressing antigen obtained from the same source
material that contains the allergen, as claim 31 requires. The simple aqueous
extract of Phleum pretense pollen, moreover, was not obtained by the
process recited in claim 31.
Although we acknowledge, as noted above, that Example 6 uses the
extracted antigen “Phi p 5” to ameliorate the hypersensitivity response in the
mouse model, the hypersensitivity-inducing allergen was chicken
ovalbumin, as in Examples 1—5. Spec. 57. Example 6, therefore, like
Examples 1—5, does not describe treating a hypersensitivity response to an
allergen by administering a hypersensitivity-suppressing antigen obtained
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from the same source material that contains the allergen, as claim 31
requires.
Nor are we persuaded that Example 7 provides an adequate
description of the claimed hypersensitivity-suppressing antigens.
Specifically, as noted above, Example 7 describes isolation of a number of
antigens from Phleum pretense pollen and from mites by an overnight
extraction and multiple dialysis steps lasting several hours, followed by
crossed radio immuno-electrophoresis. Spec. 58—59. Claim 31, in contrast,
specifies that the extraction is “in an aqueous solution at pH 6—8 for a period
not exceeding 30 minutes.” Br. 14. We are not persuaded, therefore, that
Example 7 adequately describes the hypersensitivity-suppressing antigen
required by claim 31, because the antigen was not extracted within the
limited time period recited in the claim.
We note that Phi p 5, used in Example 6, appears to have been
prepared according to Example 7, and therefore is not an antigen
encompassed by claim 31. We note, moreover, that the Specification does
not characterize Phi p 5 in any way, or describe any of its properties, such
that a skilled artisan might be able to recognize members of the claimed
genus of hypersensitivity-suppressing antigens.
Moreover, contrary to Appellants’ arguments (Br. 7—11), it is
insufficient for the purposes of satisfying the written description requirement
that the procedures described in Appellants’ Specification and recited in
claim 31 might allow a skilled artisan to obtain a hypersensitivity­
suppressing antigen required by claim 31, and to sublingually administer that
antigen to suppress a type 1 hypersensitivity response, as claim 31 also
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requires. As explained in Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314
F.3d 1313, 1334 (Fed. Cir. 2003):
The enablement requirement is often more indulgent than
the written description requirement. The specification need not
explicitly teach those in the art to make and use the invention;
the [enablement] requirement is satisfied if, given what they
already know, the specification teaches those in the art enough
that they can make and use the invention without “undue
experimentation. ”
Thus, that Appellants’ Specification might enable a skilled artisan,
based on the knowledge in the art, to practice the subject matter recited in
claim 31, does not demonstrate that the Specification adequately describes,
for the purposes of § 112, first paragraph, the hypersensitivity-suppressing
antigen required by claim 31, or its method of use. See Ariad v. Lilly, 598
F.3d at 1340 (“We now reaffirm that § 112, first paragraph, contains a
written description requirement separate from enablement. . . .” (emphasis
added)); see also University of Rochester v. G.D. Searle, 358 F.3d at 927
(finding lack of written description where specification failed to include any
examples of claimed compound having desired property, despite
specification’s disclosure and claim’s recitation of assay for obtaining
compounds having desired property).
In sum, for the reasons discussed, Appellants do not persuade us that a
preponderance of the evidence fails to support the Examiner’s prima facie
case of lack of written description as to claim 31. We, therefore, affirm the
Examiner’s rejection of that claim. Because the remaining rejected claims
were not argued separately, we affirm the Examiner’s rejection as to those
claims as well. See 37 C.F.R. § 41.37(c)(l)(iv).
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SUMMARY
For the reasons discussed, we affirm the Examiner’s rejection of
claims 27, 31, 32, and 3U44 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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