Ex Parte Hausch et al

Patent Trial and Appeal Board

Nov 15, 2016

11927536 (P.T.A.B. Nov. 15, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111927,536 10/29/2007
77974 7590 11/17/2016
Stanford University Office of Technology Licensing
Bozicevic, Field & Francis LLP
1900 University Avenue
Suite 200
East Palo Alto, CA 94303
Felix Rausch
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.
STAN-258CON3
(SOl-271)
CONFIRMATION NO.
6144
EXAMINER
AUDET, MAURY A
ART UNIT PAPER NUMBER
1675
NOTIFICATION DATE DELIVERY MODE
11/17/2016 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte FELIX RAUSCH, GARY GRAY,
LU SHAN, and CHAITAN KHOSLA
Appeal2015-004105
Application 11/927,536
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving a unit dose for oral
administration comprising a pharmaceutical excipient and a purified plant or
microbial glutenase. The Examiner rejected the claims as obvious and as not
directed to patent eligible subject matter. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as the Board of Trustees of
the Leland Stanford Junior University (see App. Br. 2).
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Application 11/927,536
Statement of the Case
Background
"[I]ngestion of gluten, a common dietary protein present in wheat,
barley and rye causes disease in sensitive individuals" (Spec. i-f 2). "The
present invention relates to the discovery that certain gluten oligopeptides
[are] resistant to cleavage by gastric and pancreatic enzymes, that the
presence of such peptides results in toxic effects, and that enzymatic
treatment can remove such peptides and their toxic effects" (Spec. i-f 9).
The Claims
Claims 25-29 and 45-58 are on appeal. 2 Claim 25 is representative
and reads as follows:
25. A preparation for unit dose oral administration
comprising a pharmaceutical excipient and a purified plant or
microbial glutenase in dosages of 0.01 mg to 500 mg /kg body
weight that when ingested by a human, is effective to cleave an
ingested gluten oligopeptide having the amino acid sequence of
SEQ ID NO: 12 to fragments shorter than 8 amino acids.
The Issues
A. The Examiner rejected claims 25-29 and 45-58 under 35 U.S.C.
§ 103(a) as obvious over Robison3 (Ans. 2-7).
2 We acknowledge that Appellants identify seven claim groupings (see App.
Br. 3--4 ), but the arguments for them simply recite the added limitations and
allege they are not found in the cited references. This is insufficient to act as
a separate argument under 37 C.F.R. § 41.37. As our reviewing court held,
"the Board reasonably interpreted Rule 41.3 7 to require more substantive
arguments in an appeal brief than a mere recitation of the claim elements and
a naked assertion that the corresponding elements were not found in the
prior art." In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011).
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B. The Examiner newly4 rejected claims 25-29 and 45-58 under
35 U.S.C. § 101 as not directed to patent eligible subject matter (Ans. 21-
25).
A. 35 USC§ 103(a) over Robison
The Examiner finds that Robison teaches microbial and plant
peptidases (see Ans. 2--4), pharmaceutical carriers for oral compositions (see
id. at 4--5) including "ranges from about 0.001 to 30 mg/kg" (id. at 3) and
"unitary dosages" (id. at 5).
The Examiner finds it obvious "to use any type of plant or microbe
glutenase in an oral composition (product claimed) in Robison, because
Robison expressly teach[ es] the use of glutenase/ enzymes of plant/microbe
origin, for oral compositions" (id. at 5---6).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Robison renders the claims
obvious?
Findings of Fact
1. Robison teaches "administering a protein as therapy to
compensate for reduced or aberrant expression or activity of the protein"
(Robison 43:48-50).
2. The Specification teaches: "Glutenases of the invention include
protease and peptidase enzymes having at least about 20% sequence identity
3 Robison, K., US 6,395,889 Bl, issued May 28, 2002.
4 The newly entered § 101 rejection was properly authorized by the
TC center 1600 director (see Ans. 26).
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Application 11/927,536
at the amino acid level ... to one of the following peptidases: prolyl
endopeptidase (PEP) from F. meningosepticum" (Spec. i-f 31 ).
3. Robison teaches: "Prolyl endopeptidase (EC 3.4.21.26) (PE)
(also called post-proline cleaving enzyme). PE is an enzyme that cleaves
peptide bonds on the C-terminal side of prolyl residues. The sequence of PE
has been obtained from ... bacteria (Flavobacterium meningosepticum and
Aeromonas hydrophila); there is a high degree of sequence conservation
between these sequences." (Robison 10:6-11).
4. Robison teaches "protein ... can be incorporated into
pharmaceutical compositions suitable for administration to a subject, e.g., a
human. Such compositions typically comprise the ... protein ... and a
pharmaceutically acceptable carrier" (Robison 57:42--49).
5. Robison teaches "a therapeutically effective amount of protein
or polypeptide (i.e., an effective dosage) ranges from about 0.001 to 30
mg/kg body weight, preferably about 0.01 to 25 mg/kg body weight ... even
more preferably about 1to10 mg/kg" (Robison 60:10-15).
6. Robison teaches: "'Dosage unit form' as used herein refers to
physically discrete units suited as unitary dosages for the subject to be
treated; each unit containing a predetermined quantity of active compound
calculated to produce the desired therapeutic effect in association with the
required pharmaceutical carrier" (Robison 59:49--54).
7. Robison teaches that it "is especially advantageous to formulate
oral or parenteral compositions in dosage unit form for ease of
administration and uniformity of dosage" (Robison 59:47--49).
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Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417.
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 2-7; FF 1-7) and agree that the
claims are obvious over Robison. We address Appellants arguments below.
Appellants contend that "the art did not teach that, to detoxify gluten
proteins effectively so as to reduce their immunogenicity in humans, one
must select an enzyme with the ability to cleave a metastable gluten
oligopeptide such as that of SEQ ID NO: 12." (App. Br. 5).
We find this argument unpersuasive because the claim is drawn to a
product comprising a specific dose range for a, protease known in the prior
art, not a method for detoxification of gluten. Just as in Kao, "the only claim
element not expressly disclosed in the prior art was the previously-unknown,
yet inherent, food-effect property." In re Huai-Hung Kao, 639 F.3d 1057,
1072 (Fed. Cir. 2011). Here, the specific inherent property ofRobison's
prolyl endopeptidase (PEP) from F. meningosepticum (FF 3) was that this
enzyme functions as a glutenase (FF 2). "'[M]erely discovering and
claiming a new benefit of an old process cannot render the process again
patentable."' Kao, 639 F.3d at 1072. Cf In re Wiseman, 596 F.2d 1019,
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1023 (CCP A 1979) (rejecting the notion that "a structure suggested by the
prior art, and, hence, potentially in the possession of the public, is patentable
... because it also possesses an inherent, but hitherto unknown, function
which [patentees] claim to have discovered. This is not the law. A patent on
such a structure would remove from the public that which is in the public
domain by virtue of its inclusion in, or obviousness from, the prior art.").
Appellants contend that "[ e ]ven if one were to select an appropriate
enzyme, there is no teaching in the art of how one would select an
appropriate dosage for the detoxification of gluten" (App. Br. 6).
We find this argument unpersuasive for two reasons. First, there is no
requirement in the claims for detoxification of gluten in a patient, so that this
argument relates to an intended use that is not even recited in the claim.
However, a "mere statement of a new use for an otherwise old or obvious
composition cannot render a claim to the composition patentable." In re
Zierden, 411F.2d1325, 1328 (CCPA 1969). Second, Robison provides
specific disclosure of a preferred dose range 0.01 to 25 mg/kg body weight
(FF 5) that fully falls within the range required by claim 25. See In re
Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) ("In cases involving
overlapping ranges, we and our predecessor court have consistently held that
even a slight overlap in range establishes a prima facie case of
obviousness.") Here, where the ranges completely overlap, the Examiner
has reasonably established the prima facie case of obviousness (see FF 5).
Appellants contend that "there is nothing in the cited art that would
teach why one should select an oral formulation of an enzyme with a
selected activity, in a specific dose, for oral administration" (App. Br. 6).
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We are not persuaded because Robison specifically teaches that oral
formulations are preferred (FF 7), that unit dose formulations are preferred
(FF 6), and specifically suggests a dose range entirely overlapping with that
of claim 1 (FF 5). Thus, the ordinary artisan, following Robison's
suggestion to form protein therapies (FF 1) using known proteases (FF 3),
would have reasonably employed the oral unit dose formulations in dose
ranges suggested by Robison (FF 5-7) to achieve the oral formulation of
claim 1.
Appellants contend that "Robison is a testament to the art of saying
much and teaching little. The reference fails to provide any specific selection
and use that would guide one of skill in the art to the specific formulations of
the present claims" (App. Br. 7).
We find this argument unpersuasive because even if Robison provides
a "laundry list" of proteases, the disclosure of "a multitude of effective
combinations does not render any particular formulation less obvious."
Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989).
"[P]icking and choosing may be entirely proper in the making of a 103,
obviousness rejection." In re Arkley, 455 F.2d 586, 587 (CCPA 1972).
Appellants provide no evidence of any secondary consideration to rebut the
Examiner's obviousness position that the selection of known elements in
known amounts from Robison would have been obvious (FF 3-7).
Appellants "submit that the dosage range is not immense, in that the
claims further include the specific activity limitation regarding cleavage of a
specific gluten oligopeptide. Further, Claims 51, 54 and 58 explicitly recite a
much narrower dosage range: 1 to 500 mg" (App. Br. 7).
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We find this argument unpersuasive because Robison teaches a
preferred range of 1 to 10 mg/kg (FF 5), a smaller dose range that fully falls
within the broader disclosed range required by Appellants. Peterson, 315
F.3d at 1329. Appellants provide no evidence of any secondary
consideration with regard to the claimed dose range.
Appellants contend that "[ e ]ven if one were to select an appropriate
enzyme, there is no teaching in the art of how one would select an
appropriate dosage for the detoxification of gluten. Indeed, it is only with the
findings of the present inventors that one of skill in the art would have
understood the importance of metastable peptides" (App. Br. 8).
We are not persuaded because the claim is not drawn to a method of
gluten detoxification, but rather to a protease composition that is rendered
obvious by Robison (FF 1, 3-7). Zierden, 411 F.2d at 1328. Appellants
provide no evidence that the claimed composition would have any property
that differs from the obvious composition of Robison, in the obvious
dosages taught by Robison. Unlike the facts in Sullivan, there are no
declarations demonstrating unexpected results or showing any unexpected
properties that would provide a basis for a finding of patentability despite
Robison's disclosures. See In re Sullivan, 498 F.3d 1345, 1353 (Fed. Cir.
2007). In addition, while the Specification discloses peptides resistant to
digestion, the Specification provides only prophetic examples to show that
supplementation with proteases has any physiological effect (see Example 3,
Spec. i-fi-f 110-125, which is written in the present tense). ("[T]he examples
were written in the present tense to conform with the PTO requirements on
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prophetic examples." Atlas Powder Co. v. E.I. du Pont De Nemours & Co.,
750 F.2d 1569, 1578 (Fed. Cir. 1984)).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Robison renders the claims obvious.
B. 35 US.C. § 101
The Examiner finds that while the claimed invention is drawn to the
eligible subject matter category of product, the claims are drawn to the
judicial exception excluding patents to naturally occurring phenomena and
that "neither of the two art-recognized naturally occurring products
(enzymes (glutenases)) and pharmaceutical excipients) have been modified
in a marked/significant way beyond that found in nature" (Ans. 22).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the claims are not directed to
patentable subject matter?
Findings of Fact
8. The Specification teaches that the "term 'glutenase' refers to an
enzyme useful in the methods of the present invention that is capable, alone
or in combination with endogenous or exogenously added enzymes, of
cleaving toxic oligopeptides of gluten proteins" (Spec. i-f 29).
9. The Specification teaches that "[ c ]andidate glutenases for use in
the practice of the present invention can be obtained from a wide variety of
sources, including libraries of natural and synthetic proteins" (Spec. i-f 4 7;
emphasis added).
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10. The Specification teaches that the "glutenase proteins useful in
the practice of the present invention may also be isolated and purified in
accordance with conventional methods ... from natural sources" (Spec.
i-f 60; emphasis added).
11. The Specification teaches "the term 'unit dosage form,' refers
to physically discrete units suitable as unitary dosages for human subjects,
each unit containing a predetermined quantity of glutenase in an amount
calculated sufficient to produce the desired effect in association with a
pharmaceutically acceptable diluent, carrier or vehicle" (Spec. i-f 72).
12. The Examiner finds that one exemplary type of "pharmaceutical
excipient" is water (see Ans. 22).
Principles of Law
"'Laws of nature, natural phenomena, and abstract ideas' are not
patentable." Mayo Collaborative Services v. Prometheus Laboratories, Inc.,
132 S. Ct. 1289, 1293 (2012) (citations omitted).
In Chakrabarty, scientists added four plasmids to a bacterium,
which enabled it to break down various components of crude
oil. ... The Court held that the modified bacterium was
patentable. It explained that the patent claim was "not to a
hitherto unknown natural phenomenon, but to a nonnaturally
occurring manufacture or composition of matter-a product of
human ingenuity 'having a distinctive name, character [and]
use."' ... The Chakrabarty bacterium was new "with markedly
different characteristics from any found in nature," ... due to
the additional plasmids and resultant "capacity for degrading
oil."
In this case, by contrast, Myriad did not create anything.
To be sure, it found an important and useful gene, but
separating that gene from its surrounding genetic material is not
an act of invention.
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Ass 'nfor Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107,
2116-2117 (2013) (internal citations omitted).
Analysis
We adopt the Examiner's findings of fact and reasoning (Ans. 21-24;
FF 8-12) and agree that the claims are not directed to patentable subject
matter.
We do not find any principled difference between the claim to an
isolated nucleic acid encoding the BRCAl polypeptide in Myriad and the
instant claim 25 drawn to an isolated glutenase enzyme with an excipient in
a particular amount. See Myriad, 13 3 S. Ct. at 2113. As in Myriad,
Appellants did not create or alter the amino acid sequence of the glutenase
enzyme, and the order of the amino acids in the glutenase enzymes existed
in nature before Appellants' isolated them (FF 9-10) (indeed the amino acid
sequence order \~1as disclosed in the prior art as demonstrated by P"-obison
(FF 3)). At best, Appellants' contribution was recognizing that this natural
product may have clinical uses in certain patient populations (see Spec. i-f 9).
However, the claims are not drawn to methods of treatment of particular
conditions in particular patient populations using a glutenase enzyme
composition, but rather are drawn to the glutenase enzyme product itself.
Like Myriad and Funk Brothers, and unlike Chakrabarty, the
glutenase enzyme of claim 25 was not a creation of Appellants, but rather a
product of nature. And there is nothing markedly different between the
glutenase enzyme of claim 25 and the natural product other than that
Appellants have purified the enzyme and mixed it with water (FF 9-12).
But separating the protein from the cell is not an act of invention. See
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Myriad, 133 S.Ct. at 2117; Funk Brothers Seed Co. v. Kala Inoculant Co.,
333 U.S. 127, 132 (1948); Diamond v. Chakrabarty, 447 U.S. 303, 309
(1980).
Appellants contend that the claims do
not read on any naturally occurring substance, and, to the extent
that one can use a naturally occurring glutenase or
pharmaceutical excipient to form the preparation, the claim, as
a whole, recites a product that has markedly different
characteristics from any naturally occurring substance.
More importantly, the recitation of the amount of the purified
glutenase as determined by the weight of a subject intended to
consume a unit dose form of it, and its properties when
ingested, renders the claimed subject matter markedly different
in function and properties from any naturally occurring source
of a glutenase or pharmaceutical excipient.
(Reply Br. 3).
We do not find this argument persuasive. Claim 25 is drawn to a
composition comprising a particular amount of a glutenase enzyme in
purified form and an excipient, where the excipient may be water (FF 12).
Because Myriad expressly teaches that purification "is not an act of
invention" Myriad, 133 S. Ct. at 2117, the only difference that might be
present between any purified prior art glutenase enzyme and the claim is the
amount of enzyme present. We do not agree with Appellants that the
selection of a particular amount of glutenase enzyme in aqueous solution
renders the composition markedly different from the same glutenase enzyme
in aqueous solution that is in higher or lower amounts. And the
Specification clearly identifies the glutenase enzyme as a natural product
(FF 9--10).
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If the amount of a naturally occurring product alone was sufficient to
render the composition markedly different, then Myriad could have simply
recited a requirement for an amount of nucleic acid sufficient to permit
polymerase chain detection of breast cancer to avoid the patentable subject
matter issue, a result we think stands in opposition to the position of the
Supreme Court. Indeed, a logical extension of Appellants' position would
allow a patent on thirty pieces of purified silver, if that were a novel and
unobvious amount determined to be the particular value of purified currency
necessary to induce betrayal.
Appellants also contend:
This claim does not "tie up" the natural product, i.e. glutenases
having the stated biological effect. The art is free to use such
glutenases in non-purified form, in dosages containing amounts
outside of those recited, for any purpose not requiring oral
administration to a human, and for any preparation not suitable
for oral administration, and so forth.
(Reply Br. 4 ).
We do not find this argument persuasive. Because the claims are
open to any human, who may weigh anywhere between about 260 g at birth
to about 442 kg in body weight, claim 25 broadly encompasses any aqueous
composition comprising between 0.0026 mg and 221,000 mg. This broad
range reasonably ties up a very significant number of enzymes at a very
wide range of amounts for a number of purposes. Because the claim is to a
product, not a process, there is no constraint on the purpose for which the
product is being used.
Appellants then address twelve factors identified in The Guidance For
Determining Subject Matter Eligibility Of Claims Reciting Or Involving
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Laws of Nature, Natural Phenomena, & Natural Products (Guidance), dated
March 4, 2014, and contend that the factors weighing toward eligibility are
satisfied or not relevant, and that the factors weighing against eligibility are
not satisfied (see App. Br. 5-8). We do not specifically address these factors
because they simply attempt to summarize Myriad, and address the issue of
whether the natural product at issue satisfies Myriad' s test of a product that
is "markedly different" from the natural product. Myriad, 133 S. Ct. at
2117. We have already determined that the claimed glutenase enzyme and
water product is not markedly different by virtue of the selection of a
particular dose range.
Indeed, in the most recent USPTO guidance in the May 6, 2016,
update, Subject Matter Eligibility Examples: Life Sciences, the guidance
provides an example regarding vaccines with an example claim drawn to:
"A vaccine comprising: Peptide F; and a pharmaceutically acceptable
carrier" where peptide F is a naturally occurring protein isolated from a virus
(Subject Matter Eligibility Examples at pages 2-3). The guidance states that
"mixing the peptide with a carrier such as water does not markedly change
the characteristics of either component, because each component continues
to have the same properties in the mixture as it had alone" and concludes
that the "claim does not qualify as eligible subject matter" (Subject Matter
Eligibility Examples at page 5).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
claims are not directed to patentable subject matter.
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SUMMARY
In summary, we affirm the rejection of claim 25 under 35 U.S.C.
§ 103(a) as obvious over Robison. Claims 26-29 and 45-58 fall with claim
25. 37 C.F.R. § 41.37(c )(1 )(iv)
We affirm the rejection of claim 25 under 35 U.S.C. § 101 as not
directed to patent eligible subject matter. Claims 26-29 and 45-58 fall with
claim 25. 37 C.F.R. § 41.37(c)(l)(iv)
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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