Ex Parte Simard

Patent Trial and Appeal Board

Feb 3, 2016

12888534 (P.T.A.B. Feb. 3, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/888,534 09/23/2010
88684 7590 02/05/2016
XBiotech, Inc,
5425 Park Central Court
Suite 111
Naples, FL 34109
FIRST NAMED INVENTOR
John Simard
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
5407-0057 4632
EXAMINER
SZPERKA, MICHAEL EDWARD
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/05/2016 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
Appeal2013-007010
Application 12/888,534
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
r-T"I .. • • .. 1 .. ,..... ,_ TT r'1 I'\ l\ -1,..... Al • "1 • "1 • , ,.. .. ims 1s an appear unaer j) u.~.L. s U4 mvo1vmg crnm1s to a memoa
of selecting a human or humanized monoclonal antibody for administration.
The Examiner rejected the claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
1 Appellant identifies the Real Party in Interest as XBiotech, Inc.
(see App. Br. 3).
Appeal2013-007010
Application 12/888,534
Statement of the Case
Background
The "invention relates to the selection of prophylactic or therapeutic
Abs based on allotypic phenotype for the reduction of adverse reactions
associated with anti-Ab responses" (Spec. i-f 2).
The Claims
Claims 1-9 and 11-15 are on appeal. Claims 1 and 9 are
representative and read as follows:
1. A method of selecting a human or humanized
monoclonal antibody for administration to a human subject
having antibodies that specifically bind an allotypic determinant
of a human immunoglobulin not endogenously present in the
subject, the method comprising the steps of:
(a) determining the presence of a first antibody allotypic
phenotype in the subject; and
(b) selecting a monoclonal antibody to be administered to
the subject from a set of human or humanized monoclonal
antibodies comprising at least a first monoclonal antibody
comprising the first allotypic phenotype and a second
monoclonal antibody comprising a second allotypic phenotype
endogenously not present in the subject; and
( c) administering the first monoclonal antibody to the
subject.
9. A method of selecting a monoclonal antibody for
administration to a human subject belonging to a defined
population, the method comprising the steps of:
(a) determining a defined population that comprises the
subject;
(b) selecting a monoclonal antibody for administration to
the subject from a set of human or humanized monoclonal
antibodies comprising at least a first monoclonal antibody
comprising a first allotypic phenotype more common in the
defined population and a second monoclonal antibody
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Application 12/888,534
comprising a second allotypic phenotype less common in the
defined population than the first allotypic phenotype; and
( c) administering the first monoclonal antibody to the
subject, wherein the first monoclonal antibody comprises a first
haplotype more common in the defined population and the
second monoclonal antibody comprises a second haplotype less
common in the defined population than the first haplotype.
The Issues2
A. The Examiner rejected claims 1-9 and 11-15 under 35 U.S.C.
§ 103(a) as obvious over Gorman3 (Non-Final Act. 1/3/2012 6-7).
B. The Examiner rejected claims 1-9 and 11-15 under 35 U.S.C.
§ 103(a) as obvious over Mage4 (Non-Final Act. 1/3/2012 8-9).
C. The Examiner rejected claims 1-9 and 11-15 under 35 U.S.C.
§ 103(a) as obvious over Clark5 (Final Act. 6/18/2012 12).
D. The Examiner rejected claims 1-9 and 11-15 under 35 U.S.C.
§ 103(a) as obvious over Jefferis6 (Non-Final Act. 1/3/2012 7-8).
E. The Examiner rejected claims 1-9 and 11-15 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
2 The obviousness-type double patenting rejection over copending
US Application 13/310,270 is moot in view of the abandonment of
that application on Apr. 25, 2013.
3 Gorman et al., Humanisation of Monoclonal Antibodies for
Therapy, 2 SEMINARS IN IMMUNOLOGY 457--466 (1990).
4 Mage, R., Designing antibodies for human therapies, 333
NATURE 807 (1988).
5 Clark, Humanized antibodies having modified allotypic
determinants, CURRENT OPINION IN THERAPEUTIC PATENTS 95-96
(Jan. 1993).
6 Jefferis et al., Human immunoglobulin allotypes, 1 MABS 1-7
(Aug. 2009).
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Application 12/888,534
claims 1-3 of copending Application No. 12/888,557 (Non-Final Act.
1/3/2012 10).
A-C. 35 U.S.C. § 103(a) over Gorman, Mage, and Clark
Because the same issues are dispositive for all three of these
rejections, we will consider them together.
In each rejection, the Examiner finds a teaching to allotype match
therapeutic antibodies. The Examiner finds that Gorman teaches that
"[a]dministering such allotype-matched humanized immunoglobulins would
have the advantage of being the best way to avoid an anti-immunoglobulin
response" (Non-Final Act. 1/03/2012 6). The Examiner finds that Mage
teaches "that the allotype present in the constant domain of a therapeutic
antibody should be matched to the patients' allotype prior to administration"
(Id. at 8). The Examiner finds that Clark teaches "administering an allotype-
matched antibody to avoid antiimmunoglobulin responses" (Ans. 12).
For all three rejections, the Examiner finds "it would have been
obvious to administer such isotype matched antibodies to patients already
having an anti-antibody response since such patients are a clear example to
the artisan of the problem of immunogenicity of administered antibodies
which can be solved by administering isotype-matched antibodies" (Final
Act. 10).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner's conclusion that Gorman, Mage, or Clark
render claims 1 and 9 obvious?
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Application 12/888,534
Findings of Fact
1. Clark teaches "[h ]uman IgGs consist of several different
allotypes specific for different racial groups so that humanized antibodies for
therapy could be antigenic in some people and not others. One possible way
to circumvent this problem would be to make all the different types and
match the correct type for each person" (Clark 95).
2. Gorman teaches that:
[I]f the intention of humani[ z Jing an antibody is to reduce
the antigenicity then it would seem to be an obvious course
of action to minimise differences of allotype in the constant
region at the same time as reshaping the variable region.
However on practical grounds it may not be feasible to
produce and obtain the necessary product licences for a
number of allotypic variants of every therapeutic antibody
so that each patient can be matched with the appropriate
antibody. One alternative is to just produce the most
frequent allotype in the population and to accept that some
patients may be able to react to the allotypic differences.
(Gorman 11-12).
3. Gorman teaches that "a fully reshaped and allotype matched
antibody is the best way of avoiding the antiglobulin response" (Gorman
15).
4. Mage teaches that "those planning clinical studies consider Km
and Gm matching their recipients with the therapeutic antibodies. . . . It will
be considerable interest and benefit if allotype-matching prolongs the time
period of effective therapy by diminishing anti-idiotype responses" (Mage
807, col. 3 to 808, col. 1 ).
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Principles of Law
"In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima face case of obviousness
based upon the prior art." In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992).
To establish a prima facie case of obviousness, the examiner must find
"a reason that would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new invention does."
KSR Int'!. Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
Claim 1
We note that claim 1 requires a subject who has already mounted an
immune response to an allotypic determinant of a non-endogenous
immunoglobulin (i.e., therapeutic antibody) and, therefore, excludes patients
who have not already received a therapeutic antibody.
Appellant contends that "neither Gorman ... Mage, nor Clark teach or
suggest 'a human subject having antibodies that specifically bind an
allotypic determinant of a human immunoglobulin not endogenously present
in the subject' (claims 1-8)" (Br. 14).
The Examiner finds that the "art does not explicitly disclose
administration of allotypically matched antibodies to a person who has
already developed an anti-antibody response specific for an administered
antibody" (Ans. 4). The Examiner finds that "administering allotypically-
matched antibodies to a person who has already developed an anti-antibody
response specific for an administered antibody, such as the patient of claim
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1, flows logically from the teachings of the art and would have been obvious
to ordinary artisans" (Ans. 5).
We find that Appellant has the better position. While we agree with
the Examiner that common sense may be used to demonstrate obviousness,
that common sense must be consistent with the teachings of the references.
Clark, Gorman, and Mage never describe the scenario envisaged by the
Examiner of a patient who has already developed an anti-antibody response
(see Ans. 4), but rather simply recognize the existence of multiple allotypes
and suggest different approaches to resolve this concern.
Clark teaches making all of the different allotypes to match patient to
allotype and avoid anti-antibody responses (FF 1 ). Gorman also recognizes
the concept of making all allotypes, but suggests "to accept that some
patients may be able to react to the allotypic differences" (FF 2). Mage also
simply teaches allotype matching, without any suggestion to use a different
allotype in a patient who has already mounted an anti-antibody response (FF
4).
When the Board makes "core factual findings in a
determination of patentability," it "cannot simply reach
conclusions based on its own understanding or experience--
or on its assessment of what would be basic knowledge or
common sense." In re Zurko, 258 F.3d 1379, 1386 (Fed.Cir.
2001 ). Instead, "the Board must point to some concrete
evidence in the record in support of these findings." Id.
In re Wallen, 565 Fed. Appx. 867, 869 (Fed. Cir. 2014). We are not
persuaded that Clark, Gorman, or Mage provide sufficient concrete evidence
of obviousness for claim 1.
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Claim 9
Appellant contends that "neither Gorman ... Mage, nor Clark teach or
suggest ... the limitation 'wherein the first monoclonal antibody comprises
a first haplotype more common in the defined population and the second
monoclonal antibody comprises a second haplotype less common in the
defined population than the first haplotype.' (Claims 9 and 11-15)" (Br. 14).
The Examiner finds that "determining the allelic phenotype of a
patient, as is done in the methods of the prior art and claim 1 necessarily
assign a patient to a population, namely the population comprising the
allotype which is present in the patient" (Ans. 7).
We find that claim 9 is obvious over the teachings of Gorman, Mage,
or Clark. Unlike claim 1, claim 9 does not require a patient already exposed
to a therapeutic antibody, but rather simply requires administering a
therapeutic antibody where "the first monoclonal antibody comprises a first
haplotype more common in the defined population" (Claim 9).
Gorman expressly teaches to "just produce the most frequent allotype
in the population and to accept that some patients may be able to react to the
allotypic differences" (FF 2), directly suggesting administering an antibody
with the most common allotype. Clark and Mage also teach the use of
antibodies that may be antigenic in some people and not in others, and
suggests that allotyping for each patient would be expensive (FF 1, 4), a
finding that reasonably suggests producing the more common allotypes to
avoid unnecessary expense.
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Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Gorman, Mage, or Clark render claim 1 obvious.
The evidence of record supports the Examiner's conclusion that
Gorman, Mage, or Clark render claim 9 obvious.
D. 35 U.S.C. § 103(a) over Jefferis
The Examiner finds that Jefferis teaches "it is inevitable that patients
will be administer[ ed] antibodies for which the constant domain sequence is
not native (i.e. allotype mismatch) and that such allotypic differences can
contribute to and/or potentiate immunogenicity" (Non-Final Act. 1/03/2012
7). The Examiner finds that Jefferis suggests "determining the allotypes
present in the patient, making an antibody with two or more allotypic
variants which share the same constant domain, and administering the
variant with the appropriate matching allotype to the patient" (Id. at 7-8).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner's conclusion that Jefferis renders claims 1 and 9
obvious?
Findings of Fact
5. Jefferis teaches that "[m]ore than twenty recombinant
monoclonal antibodies are approved as therapeutics. Almost all of these are
based on the whole IgG isotype format" (Jefferis 1, abstract).
6. Jefferis teaches that:
Polymorphisms (allotypes) within the IgG isotype were
originally discovered and described using serological
reagents derived from humans; demonstrating that allotypic
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variants can be imnmnogenic and provoke antibody
responses as a result of allo-immunization. The serologically
defined allotypes differ widely within and between
population groups; therefore, a mAb of a given allotype will,
inevitably, be delivered to a cohort of patients homozygous
for the alternative allotype.
(Jefferis 1, abstract).
7. Jefferis teaches that a "feature of all rP/rGP is a potential to be
immunogenic i.e., cause the generation of anti-therapeutic antibodies (AT A).
Such antibodies may neutralize the therapeutic, result in enhanced clearance
or precipitate severe adverse reaction" (Jefferis 1, col. 2).
8. Jefferis teaches that:
When an AT A is detected it is advised that the isotype
profile of the AT A be determined; we suggest that
preliminary epitope specificity might also be informative
and that it should include distinction between variable
region structure and constant region allotypy. Should anti-
allotype responses be encountered, the development of two
or more allotypic variants would be indicated.
(Jefferis 6, col. 1 ).
9. Jefferis teaches that "IgG 1 mAb therapeutics of both
predominant aIIotypes are licensed and in the market place" (Jefferis 5, col.
2).
Analysis
Claim 1
We recognize, but find unpersuasive, Appellant's argument that
Jefferis does not "teach or suggest 'a human subject having antibodies that
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specifically bind an allotypic determinant of a human immunoglobulin not
endogenously present in the subject' (claims 1-8)" (Br. 14 ).
Jefferis teaches therapeutic antibodies (FF 5) whose administration
may generate anti-therapeutic antibodies (FF 7) because of the therapeutic
antibody allotype (FF 6). Jefferis specifically suggests that when an anti-
therapeutic antibody is detected, thus necessarily in a patient, "the
development of two or more allotypic variants would be indicated" (FF 8).
Jefferis' suggestion to develop an additional allotypic variant directly
contemplates the administration of that newly developed allotypic variant to
the original patient with the anti-therapeutic antibody. This reasoning is
consistent with the Examiner's finding that a "patient who already has
developed an anti-antibody response to an allotypic determinant of an
administered antibody ... also reasonably needs the antibody medication"
(Ans. 5).
Claim 9
We recognize, but find unpersuasive, Appellant's argument that
Jefferis does not "teach or suggest ... the limitation 'wherein the first
monoclonal antibody comprises a first haplotype more common in the
defined population and the second monoclonal antibody comprises a second
haplotype less common in the defined population than the first haplotype.'
(Claims 9 and 11-15)" (Br. 14).
Jefferis provides objective evidence that when anti-therapeutic
antibodies are detected, the constant region allotypy should be determined
and new allotypic variants developed (FF 8). Moreover, Jefferis evidences
that the most common allotypes are currently in use in antibody therapeutics
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(FF 9). The Examiner's reasoned position that the most common antibody
allotypic variants would be selected for production is based within the logic
of Jefferis itself, and does not represent hindsight.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Jefferis renders claims 1 and 9 obvious.
E. Double Patenting
We summarily affirm the obviousness-type double patenting rejection.
See Manual of Patent Examining Procedure§ 1205.02 ("If a ground of
rejection stated by the examiner is not addressed in the appellant's brief, that
ground of rejection will be summarily sustained by the Board.")
SUMMARY
In summary, we reverse the rejection of claims 1-8 under 35 U.S.C.
§ 103(a) as obvious over Gorman, Mage, or Clark.
We affirm the rejection of claim 9 under 35 U.S.C. § 103(a) as
obvious over Gorman, Mage, or Clark. Claims 11-15 fall with claim 9.
37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claims 1 and 9 under 35 U.S.C. § 103(a) as
obvious over Jefferis. Claims 2-8 and 11-15 fall with claims 1 and 9.
37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claims 1-9 and 11-15 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1-3 of copending Application No. 12/888,557.
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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
lp
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