ELANCO US INC.

Patent Trials and Appeals Board

Mar 10, 2021

2020003895 (P.T.A.B. Mar. 10, 2021)

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.
15/436,404 02/17/2017 David M. ANDERSON X19595D 4086
159715 7590 03/10/2021
Elanco US Inc.
Patent Division
2500 Innovation Way
Greenfield, IN 46140
EXAMINER
PAGUIO FRISING, MICHELLE F
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
03/10/2021 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):
patents@elanco.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DAVID M. ANDERSON, HUMG-YU HSIAO, and LIN LIU
____________

Appeal 2020-003895
Application 15/436,404
Technology Center 1600
____________

Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to methods of improving animal growth performance and/or reducing
immune stress in an animal comprising oral administration of a composition
containing a bacterial alkaline phosphatase (“AP”) that have been rejected as
obvious under 35 U.S.C. § 103 and for obviousness-type double patenting
(“ODP”). We have jurisdiction 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 Elanco US Inc. as the real party in
interest. Appeal Br. 2. Herein, we refer to the Final Action mailed May 22,
2019 (“Final Act.”); Appellant’s Appeal Brief filed January 23, 2020
(“Appeal Br.”); Examiner’s Answer mailed March 16, 2020 (“Ans.”); and
Appellant’s Reply Brief filed April 29, 2020 (“Reply Br.”).
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STATEMENT OF THE CASE
Claims 21 and 27 are on appeal and can be found in the Claims
Appendix of the Appeal Brief. Claim 21 is representative and reads as
follows:
21. A method of improving animal growth performance and/or
reducing immune stress in an animal, comprising orally
administering to said animal a composition comprising an
immune stress-reducing enzyme in an orally acceptable carrier,
wherein said composition is selected from the group consisting
of:
(i) an animal feed comprising at least 20 IU of said
immune stress-reducing enzyme/kg feed;
(ii) a liquid composition other than an animal feed
comprising at least 2,000,000 IU of said immune stress-reducing
enzyme/L; and
(iii) a solid composition other than an animal feed
comprising at least 40,000 IU of said immune stress-reducing
enzyme/kg;
wherein said immune stress-reducing enzyme is a bacterial
alkaline phosphatase.
Appellant seeks review of the following rejections:
I. Claim 21 under 35 U.S.C. § 103 as unpatentable over Brands2 and
Poelstra;3
II. Claims 21 and 27 under 35 U.S.C. § 103 as unpatentable over
Brands, Poelstra, and Anderson;4 and
III. Claims 21 and 27 for ODP over claims 22–43 and 45 of the ’782
patent5 in view of Brands and Poelstra.

2 WO 2005/074978 A1, published Aug. 18, 2005 (“Brands”).
3 US 6,290,952 B1, issued Sept. 18, 2001 (“Poelstra”).
4 US 2004/0223961 A1, published Nov. 11, 2004 (“Anderson”).
5 US 7,914,782 B2, issued Mar. 29, 2011 (“the ’782 patent”).
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See Appeal Br. 4–11.
Findings of Fact
FF1. Brands teaches that lipopolysaccharides (“LPS”) from bacteria “are
toxic to most mammals” and produce a “range of biological effects,”
including “production of cytokines and chemokines” that “attract and activate
cells of the immunes system, which may culminate ultimately in an LPS
induced systemic inflammatory response syndrome (SIRS).” Brands, 1:11–
24.
FF2. Brands teaches that “Alkaline phosphatase (AP), has been described
earlier as a key enzyme in the dephosphorylation of LPS (endotoxin) under
physiological conditions both in vitro and in vivo as a natural response to
detoxify and neutralize LPS.” Id. at 3:10–13 (citing Poelstra); see also id. at
8:31–9:1 (“The exact physiological function of the AP are not known, but AP
appears to be involved with a large number of physiological processes,
among which the detoxification of LPS through dephosphorylation of the
toxicity determining lipid A moiety of LPS.”).
FF3. Brands teaches administration of AP “for the prophylaxis or treatment
of LPS mediated or exacerbated diseases.” Brands, Abstr. Brand teaches
that AP is administered to detoxify, neutralize, etc., LPS before it can elicit
an inflammatory response, making it useful to treat inflammatory diseases.
Id. at 6:31-7:2; 10:30–31. More specifically, Brands teaches:
methods and compositions for the detoxification of LPS in situ
at mucosal tissues in body cavities. A first aim of the in situ
deto[x]ification of LPS at mucosal surfaces in the body is to
prevent or reduce local inflammatory response at such surfaces.
Furthermore, the LPS that is thus detoxified is no longer
available for passage through mucosal layers and thus cannot
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enter the circulation where it will exert its toxic effects and/or
cause a further local and/or systemic inflammatory response.
Id. at 9:20–26.
FF4. Brands teaches that “[i]n a preferred embodiment the method
comprises oral administration of a source of AP to reduce LPS toxicity at
and/or passage of LPS through the mucosa.” Id. at 11:14–16.
FF5. Brands teaches that “[a] source of AP can be any AP enzyme, or any
composition comprising the AP enzyme and any means which is capable of
producing a functional AP enzyme in the context of the current invention,
such as DNA or RNA nucleic acids encoding an AP enzyme.” Brands, 9:29–
32. According to Brands, “native or recombinant micro-organisms, such as
bacteria, fungi, protozoa and yeast may be applied as a source of AP in the
context of the current invention.” Id. at 10:2–4.
FF6. Brands teaches that the “AP containing composition for oral
administration of AP to the mucosa of the gastrointestinal tract” may be an
AP enriched “food product” or a “dairy product” such as milk. Brands,
15:29–16:19.
FF7. Brands describes examples in which mice were administered AP in
their drinking water at a “single oral dosage of 75,000 U/kg BIAP [bovine
intestinal AP] per oral gavage (in 250 μl autoclaved drinking water).”
Brands, 24:8–9.
FF8. Poelstra teaches that AP has “endotoxin detoxifying activity, even at
physiological pH levels.” Poelstra, 5:20–23. Poelstra discusses certain AP
derivatives taught in the prior art, including a “recombinant E. coli alkaline
phosphatase with a substitution of Ala 103 by Asp.” Id. at 13:59–61.
FF9. Claim 22 of the ’782 patent teaches:
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A method of improving animal growth performance and/or
reducing immune stress in an animal, comprising orally
administering to said animal a composition comprising an
immune stress reducing enzyme in an orally acceptable carrier,
wherein said composition is selected from the group consisting
of:
(i) an animal feed comprising at least 20 IU 1,3-β-
glucanase/kg feed;
(ii) a liquid composition other than an animal feed
comprising at least 155,000 IU 1,3-β-glucanase/L and
(iii) a solid composition other than an animal feed
comprising at least 300,000 IU 1,3-β-glucanase/kg.
’782 patent, 41:35–46.
FF10. Claim 45 of the ’782 patent teaches that the composition of claim 22
further comprises AP as an “immune stress-reducing enzyme.” ’782 patent,
44: 1–9.
Analysis
I. OBVIOUSNESS REJECTIONS
Both obviousness rejections rely on the same combination of Brands
and Poelstra as applied to independent claim 21. See Final Act. 7.
Appellant does not present any additional argument concerning the rejection
of claim 27, but instead argues that rejection should be reversed “because
Claim 21 is non-obvious over Brands and Poelstra as described above.”
Appeal Br. 10. Accordingly, we consider these rejections together, focusing
on claim 21 as representative of the claims on appeal. See 37 C.F.R. §
41.37(c)(1)(iv). The issue is whether a preponderance of the evidence
supports Examiner’s conclusion that the cited prior art renders the method of
claim 21 obvious.
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Examiner finds Brands teaches a LPS detoxification method for
treating or preventing various LPS-mediated diseases such as inflammatory
bowel syndrome, SIRS, and autoimmune diseases, comprising the oral
administration of a source of AP. Ans. 4–5. Examiner determines that
Brands’ method “satisfies the intended function ‘improving animal growth
performance and/or reducing immune stress in an animal’” as recited in
claim 21. Id. at 6. Examiner further finds that the embodiment in Brands’
working examples involving “providing alkaline phosphatase in water
amounting to 75,000 U/kg in 250 μl drinking water or 6,000,000 U/L meets
‘wherein said composition is selected from the group consisting of . . . (ii) a
liquid composition other than an animal feed comprising at least 2,000,000
IU of said immune stress-reducing enzyme/L,’” as recited in claim 21. Id.
Examiner acknowledges that the AP in Brands’ examples is bovine
intestinal alkaline phosphatase, not a bacterial phosphatase as claimed, but
notes Brand teaches “the source of alkaline phosphatase can be native or
recombinant microorganisms like bacteria.” Ans. 6, 11. “Bacterial AP is
therefore acknowledged by Brands as an alternative to bovine intestinal AP.”
Id. at 11. Examiner further finds that “[b]acterial sources of alkaline
phosphatase are known in the art” citing Poelstra’s disclosure of
recombinant AP from E. coli. Id. at 6. Accordingly, Examiner concludes
the use of bacterial AP in Brands’ LPS detoxification method would have
been an obvious “substitution of one known element for another [that] would
obtain predictable results.” Id. at 12.
We agree with and adopt Examiner’s findings of fact and conclusion
of obviousness as articulated in the Final Action and Answer (Final Act. 3–
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10; Ans. 3–8, 10–15; FF1–8). As explained below, we are not persuaded by
the Appellant’s arguments to the contrary.
Appellant argues that Examiner has misread Brands to teach “that
native micro-organisms, such as bacteria, may be a source of AP”
administered in its method. Appeal Br. 7. According to Appellant, Brands’
“description of nucleic acids encoding AP and vectors embedding those
nucleic acids leads to the question of whether micro-organisms such as
bacteria may be the source of the nucleic acids or merely ‘be applied as’ a
means of expressing an AP, such as a mammalian AP.” Id.; see also Reply
Br. 3 (arguing “the proper interpretation” of Brands “is that bacteria may be
used to recombinantly produce mammalian AP for use in the treatment of
mammals”). Appellant points out that Brands “states the AP is preferably
‘an eukaryotic AP, more preferably a mammalian AP’” and “cites Poelstra
as evidence that endogenous (e.g. mammalian) alkaline phosphatases are
important in the detoxification of LPS.” Appeal Br. 7 (citing Brands, 3:10–
13, 15:16–19). For these reasons, Appellant urges that the terms “present
invention” or “current invention” in Brands should be interpreted as limiting
the source of AP taught there to non-bacterial sources. Id. at 7–8 (citing
Forest Labs., LLC v. Sigmapharm Labs., LLC, 918 F.3d 928, 933 (Fed. Cir.
2019) (“Forest Labs”)).
Appellant’s arguments are not persuasive. Brands teaches that the
source of AP for its method can be any AP enzyme. FF5. Moreover,
Brands expressly teaches that “native” microorganisms such as bacteria can
be used as the source of AP. Id. For this reason, we disagree with
Appellant’s suggestion that Brands can be fairly read to suggest that bacteria
are mentioned merely as a means of expressing or producing mammalian
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AP. Rather, Brands clearly and unequivocally teaches that the source of AP
administered in its LPS detoxification method may be bacterial AP, either a
“native” bacterial AP or a “recombinant” bacterial AP derivative. FF5.
Appellant’s argument that the authors of Brands preferred eukaryotic
or mammalian AP to bacterial AP is also unpersuasive. “[I]n a section 103
inquiry, ‘the fact that a specific [embodiment] is taught to be preferred is not
controlling, since all disclosures of the prior art, including unpreferred
embodiments, must be considered.” Merck & Co., Inc. v. Biocraft Labs.,
Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d
747, 750 (CCPA 1976)). As explained above, Brands teaches that any AP,
including AP from a native bacterial source, can be used. FF5. The fact that
the authors of Brands may have preferred mammalian AP does not make the
use of bacterial AP any less obvious. See Merck, 874 F.2d at 807
(explaining that a reference’s disclosure of “a multitude of effective
combinations does not render any particular formulation less obvious”).
Forest Labs is a claim construction case and does not support
Appellant’s position. There, our reviewing court affirmed the district court’s
construction that claims, which did not expressly recite buccal or sublingual
administration, were nonetheless limited to such based on statements in the
specification describing such modes of administration as “the invention.”
Forest Labs, 918 F.3d at 933. Here, however, Appellant seeks to disregard
certain teachings in Brands’ specification, i.e., that the source of AP can be
any AP enzyme, including a bacterial one. FF5. Nothing in Forest Labs
counsels such a result.
Appellant’s arguments concerning Examiner’s interpretation of
Poelstra (see Appeal Br. 8–9) are also unpersuasive. Examiner cites Poelstra
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as evidence that bacterial sources of AP were known in the art. Poelstra
supports that finding. FF8. But even if it did not, we determine that the
teachings in Brands alone are sufficient to support a prima facie showing of
obviousness.6 Appellant has not provided persuasive evidence or argument
to overcome that showing.
Finally, Appellant argues that Examiner “over-estimates the
expectation of success in using AP to improve animal growth performance
and/or reduce immune stress by oral administration” because “Example 4 of
Brands teaches that only 6-14% of a single large bolus of AP remains active
and bioavailable in the intestines and colon.” Appeal Br. 9. We are not
persuaded. As Examiner observes, claim 21 does not require any particular
degree of activity or bioactivity or dosage regimen. Ans. 15. Appellant has
not provided evidence that the amounts of AP described in Brand would not
be effective in reducing immune stress in animals, when Brand expressly
teaches the purpose of AP administration is to detoxify, neutralize, etc., LPS
before it can elicit an inflammatory response. FF3. In addition, Brands
explains that the bioavailability values Appellant relies upon “are probably
grossly underestimated, because values are from individual mice at a given
time point and do not represent alkaline phosphatase activity throughout the
tract of one mouse followed in time.” Brands 26:10–13. Indeed, contrary to
Appellant’s argument that the results in Brands’ Example 4 suggest a skilled
artisan would lack a reasonable expectation of success, Brands teaches these
results “clearly demonstrate local bioavailability of AP” and therefore

6 We note the Board may rely on less than all of the references applied by
the Examiner in an obviousness rationale without designating it as a new
ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
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“underscore the feasibility of the method of the current invention.” Id. at
26:15–17. Thus, the record supports Examiner’s finding that a skilled
artisan would have had at least a reasonable expectation of success in view
of these findings and the other teachings in Brands.
For these reasons, we determine that Examiner’s rejection of claim 21
as obvious is supported by a preponderance of the evidence. Appellant does
not present any additional arguments for claim 27. We therefore affirm the
obviousness rejections of both claims.
II. ODP REJECTION
The issue for this rejection is whether a preponderance of the evidence
supports Examiner’s conclusion that Appellant’s claims would have been
obvious over claims 22–43 and 45 of the ’782 patent in view of Brands and
Poelstra.
Examiner finds that reference claim 22 of the ’782 patent (FF9) is
“drawn to a method of improving animal growth performance and/or
reducing immune stress in an animal” comprising a composition as recited in
present claims 21 and 27 except that the composition in reference claim 22
comprises 1,3-β-glucanase. Ans. 16. Examiner further determines that
reference claim 45 teaches that the composition of claim 22 further
comprises AP as an immune stress-reducing enzyme. Id. at 16. Examiner
relies on the same findings noted above concerning the teachings in Brands
and Poelstra to conclude that it would have been obvious to use a bacterial
AP in the recited amount as the AP in the composition of reference claim 45.
Id.
We agree with Examiner’s findings and conclusion of obviousness as
articulated in the Answer. See Ans. 9–10, 16; FF1–10.
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Appellant’s argument that it would not have been obvious to
substitute one immune stress-reducing enzyme (i.e., 1,3-β-glucanase) for
another (i.e., AP) is not persuasive. See Appeal Br. 11. Claim 45 of the
’782 patent teaches the administration of both enzymes. FF10. Appellant’s
present claims 21 and 27 do not exclude administration of another enzyme
such as 1,3-β-glucanase in addition to AP. Accordingly, Examiner’s ODP
finding is supported by the record and does not require the substitution of
AP for 1,3-β-glucanase.7
Appellant also asserts that the ODP “rejection is based on a
misreading and misinterpretation of Brands and Poelstra and a
misapplication of the legal basis for the prohibition against non-statutory
patenting,” but does not elaborate on those arguments. See Appeal Br. 11.
To the extent Appellant intends to rely on the same arguments it made
against the obviousness rejections for the ODP rejection, we are not
persuaded by those arguments for the reasons explained above. Any other
arguments have been waived because Appellant has failed to sufficiently
“explain why the examiner erred” in its Appeal Brief. See 37 C.F.R. § 41.
37(c)(1)(iv).
For these reasons, we determine that Examiner’s ODP rejection is
supported by a preponderance of the evidence. Therefore, we affirm.

7 Examiner “[a]lternatively” finds that it would have been obvious to replace
1,3-β-glucanase with AP. Ans. 10. We need not reach this finding because
Examiner’s primary finding, i.e., that reference claim 45 teaches the
administration of both enzymes for the same purpose, is supported by the
record.
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CONCLUSION
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
21 103 Brands, Poelstra 21
21, 27 103 Brands, Poelstra,
Anderson
21, 27
21, 27 Obviousness-type
Double Patenting
21, 27
Overall
Outcome
21, 27

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

AFFIRMED