Albert Abraham

Patent Trials and Appeals Board

Sep 6, 2019

13320289 - (D) (P.T.A.B. Sep. 6, 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.
13/320,289 11/14/2011 Albert Abraham BHC 097002 BAYR6427 7634
71396 7590 09/06/2019
BAYER HEALTHCARE LLC (AH)
1 Bayer Drive
Indianola, PA 15051
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
09/06/2019 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):
USPOCCS@BAYER.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte ALBERT ABRAHAM1
____________

Appeal 2018-005406
Application 13/320,289
Technology Center 1600
____________

Before ERIC B. GRIMES, DEBORAH KATZ, and RYAN H. FLAX,
Administrative Patent Judges.

FLAX, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims to methods for administering an immunomodulator composition to an
egg in ova (aka, in ovo).2 The Examiner’s rejection of claims 34–40 and 49
under 35 U.S.C. § 103(a) remains appealed.3 We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.

1 Appellant identifies the real party-in-interest as, “Bayer Intellectual
Property GMBH.” Appeal Br. 1.
2 The Specification refers to “in ovo” administration and the claims recite “in
ova” administration, which are synonymous terms.
3 As of the filing of this appeal, claims 1–26 and 28–33 stand cancelled and,
in the Reply Brief, Appellant withdrew the appeal as to claims 27, 41–48,
and 50. Final Action 2; Reply Br. 1.
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In the Reply Brief, Appellant states, “Appellant requests that the
appeal be withdrawn with respect to claims 27, 41 through 48, and 50 and
proceed on the basis of claim 35 and claims 34, 36 through 40, and 49
dependent therefrom.” Reply Br. 1. We, therefore, summarily dismiss this
appeal with respect to claims 27, 41–48, and 50 and herein consider the
outstanding rejection as it applies to claims 34–40 and 49.
STATEMENT OF THE CASE
The Specification states, “[t]he present invention relates to a method
of immune activation in an avian species.” Spec. 1:3.4 The Specification
further states:
Some live viral vaccines can be administered in eggs before the
birds hatch. This procedure is referred to as “in ovo
vaccination.” The in ovo vaccinated birds develop resistance to
the target disease. However, many vaccines used for hatched
birds cannot be used for in ovo vaccination due to the embryonic
pathogenicity of the vaccine agents. Late stage embryos are
highly susceptible to infection with most vaccine viruses
examined.
Id. at 2:7–11. Further, “a need exists for a method of eliciting a non-antigen-
specific immune response that enhances protection of birds from infectious
disease and is easy to administer.” Id. at 2:20–22.
As set forth below, the claimed invention is directed to administering
a composition including a cationic liposome and a non-coding (for
immunogen) nucleic acid molecule to elicit such an immune response. The
Specification states, “[a] suitable liposome delivery vehicle comprises a lipid

4 When referencing the Specification or “Spec.” we refer to the Specification
filed as PCT/EP2010/002809 on November 14, 2011.
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composition that is capable of delivering nucleic acid molecules to the
tissues of the treated subject,” and explains, “[s]uitable liposomes include
any liposome, such as those commonly used in, for example, gene delivery
methods known to those of skill in the art,” for example, “cationic liposome
compositions.” Spec. 9:29–30, 10:21–27. The Specification states, “[a]
suitable nucleic acid molecule includes any nucleic acid sequence such as
coding or noncoding sequence, and DNA or RNA,” specifically, “such as a
plasmid vector without a gene insert.” Id. at 11:1–8. The Specification
states, “[c]omplexing a liposome with a nucleic acid molecule may be
achieved using methods standard in the art.” Id. at 11:15–16. The
Specification states, “protecting a subject from a disease is accomplished by
eliciting an immune response in the member of the avian species by
inducing a beneficial or protective immune response.” Id. at 14:20–22.
Independent claim 27 and dependent claim 35, reproduced below, are
representative:
27. A method of increasing hatchability of an
embryonated chicken egg comprising administering in ova to the
egg from about 0.05 to about 10 micrograms of an
immunomodulator composition prior to hatching, wherein the
immunomodulator composition comprises:
a. a cationic liposome delivery vehicle; and
b. a nucleic acid molecule that does not code for an
immunogen,
wherein said administration increases the hatchability of
said egg following challenge with Escherichia coli.
35. The method of claim 27, wherein the nucleic acid
molecule is a DNA plasmid.
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Supplemental Appeal Br. 2 (Claims Appendix). Although the rejection of
claim 27 is no longer appealed (see supra n.3), claims 34–40 and 50 depend
therefrom.
The following rejection is on appeal:
Claims 27 and 34–50 stand rejected under 35 U.S.C. § 103(a) over
Gomis,5 Dow,6 and Zaks.7 Final Action 9.
FINDINGS OF FACT
We adopt the Examiner’s findings of fact and rationale on
obviousness as set forth in the Final Action and Answer. Final Action 2–5;
Answer 3–15. The following findings of fact highlight certain evidence:
FF1. Gomis discloses “[o]ligodeoxynucleotides (ODN)
containing cytosine-phosphodiester-guanine (CpG) motifs [“CpG
ODN”] have been shown to be effective immunoprotective agents”
and discloses a study where “embryonated [chicken] eggs that had
been incubated for 18 or 19 days, received 50 µg CpG ODN.” Gomis
813 (abstract).
FF2. Gomis discloses that chick
groups that received CpG ODN, either by intramuscular or in ovo
routes, had significantly higher survival rates (P < 0.0001) [post-

5 Susantha Gomis et al., Protection of Neonatal Chicks Against a Lethal
Challenge of Escherichia coli Using DNA Containing Cytosine-
Phosphodiester-Guanine Motifs, 48 AVIAN DISEASES 813–822 (2004)
(“Gomis”).
6 Steven W. Dow, DVM, PhD, Liposome-Nucleic Acid Immunotherapeutics,
5(1) EXPERT OPIN DRUG DELIV. 11–24 (2008) (“Dow”).
7 Karen Zaks et al., Efficient Immunization and Cross-Priming by Vaccine
Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic
Liposomes, 176 J. IMMUNOL. 7335–45 (2006) (“Zaks”).
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E. coli challenge]. Bacterial counts in air sacs were significantly
lower when birds or embryos were treated with CpG ODN as
compared with controls. A dose as low as 10 µg of CpG ODN,
administered intramuscularly, was able to protect birds
significantly against E. coli challenge,
thus “[t]his is the first time that CpG ODN has been demonstrated to
have an immunoprotective effect against a bacterial infection in
chicks following in ovo delivery.” Gomis 813 (abstract); see also id.
at 814 (“The objective of this study was to determine the effect of
CpG ODN, delivered either intramuscularly or in ovo, as an
immunostimulant in broiler chicks, using an E. coli infection
model.”).
FF3. Gomis teaches that “Escherichia coli causes a variety of
disease syndromes in poultry, including yolk-sac infection [i.e., an
infection in ovo], omphalitis, respiratory tract infection, swollen head
syndrome, septicemia, and cellulitis.” Gomis 814.
FF4. Gomis states, “further work on delivery mechanisms
(such as in ovo administration with encapsulation for the slow release
of CpG ODN, and aerosol or oral delivery) are necessary to expand
the utility of CpG ODN use in the poultry industry,” which suggests
that the CpG ODN should be complexed with another component for
encapsulation to control administration. Gomis 820.
FF5. Dow teaches that “liposome-nucleic acid complexes also
show promise for immunotherapy of acute . . . bacterial infections,”
and “cationic liposomes combined with nucleic acids form the basis
for a potent and versatile immunotherapeutic platform.” Dow 1
(abstract); see also id. at 9–11 (concluding that “liposomal delivery
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offers important advantages over treatment with the innate immune
receptor agonist alone” and there are “major advantages” in
complexing cationic liposomes with immunotherapeutics based on
nucleic acids).
FF6. Dow teaches that “[l]iposomes enhance innate immune
activation by nucleic acids,” and, specifically, cationic liposomes
complexed with bacterial DNA, CpG ODN, and plasmid DNA. Dow
3–4.
FF7. Zaks teaches that “[c]omplexing . . . plasmid DNA to
cationic liposomes markedly potentiates their ability to activate innate
immunity.” Zaks 7335 (abstract).
DISCUSSION
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability.
[Once] . . . that burden is met, the burden of coming forward with evidence
or argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). Arguments made by Appellants in the Appeal Brief and
properly presented in the Reply Brief have been considered; arguments not
so-presented are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex
parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any
bases for asserting error, whether factual or legal, that are not raised in the
principal brief are waived.”).
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CLAIM INTERPRETATION
The Patent Office applies the broadest reasonable construction
standard in prosecution proceedings. Cuozzo Speed Tech., LLC v. Lee, 136
S. Ct. 2131, 2145 (2016).
A claim preamble does not further limit claims if it merely states a
purpose or intended use of subject matter, but, if the preamble expresses an
“essential” characteristic of the invention necessary to point out the defined
invention, it may be said to “give life and meaning” to the claims and,
thereby, be considered a limitation. Kropa v. Robie, 187 F.2d 150, 152
(CCPA 1951). Further, “[w]here . . . a patentee defines a structurally
complete invention in the claim body and uses the preamble only to state a
purpose or intended use for the invention, the preamble is not a claim
limitation.” Rowe v. Dror, 112 F.3d 473, 478 (Fed. Cir. 1997). Moreover,
as explained at MPEP § 2111.04, a “‘whereby clause in a method claim is
not given weight when it simply expresses the intended result of a process
step positively recited.’” See Hoffer v. Microsoft Corp., 405 F.3d 1326,
1329 (Fed. Cir. 2005) (quoting Minton v. Nat’l Ass’n of Securities Dealers,
Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003)).
Much of the dispute on appeal focuses upon whether the claims
require improved chicken hatchability after eggs are challenged with E. coli.
As noted above, independent claim 27 (and, therefore, its dependent claims),
in its preamble, states that its claimed method is for “increasing hatchability
of an embryonated chicken egg,” and, as a concluding “wherein” clause,
recites that the administration step “increases the hatchability of said egg
following challenge with Escherichia coli.” Thus, an issue presented in this
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case is whether, or to what extent, this claim language limits the respective
claims.
As noted above, a preamble will not be considered a claim limitation
where it merely states a purpose or intended use of the subject matter of the
claim’s body and, also, will not be considered a claim limitation where the
body of the claim recites a complete structure or method. Here, the
preamble of claim 27 recites an intended use or result/purpose of the claimed
method. And, the body of the claim, i.e., that portion following the
transition claim term “comprising,” recites a complete method including the
single step of administering a specific composition at a specific dosage
range. Therefore, the preamble of the claim is not a limitation.
As also noted above, a “wherein” (or “whereby”) clause in a claim
does not limit a claim where it merely identifies an intended result of an
affirmative method step recited by the claim. Here, the step recited by claim
27, i.e., administering the claimed composition to a chick in ova within a
specific dosage range, is a complete method regardless of its intended result.
The claim does not recite an affirmative step of challenging such a
therapeutically treated egg with E. coli, but only that the result of such an
administration step is that it “increases the hatchability of said egg following
challenge with Escherichia coli.” Whether or not the egg is ever challenged
with E. coli, the administration step, which is the sole step of the claimed
method, would not change and its results would be effected. Therefore, the
“wherein” clause of claim 27 does not limit the claim.
We note the recent Federal Circuit decision in Allergan Sales, LLC v.
Sandoz, Inc., where two “wherein” clauses of a claim were held to have been
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correctly construed by district court to be limitations. Allergan Sales, LLC v.
Sandoz, Inc., --- F.3d ---, 2019 WL 4063570 (Fed. Cir. Aug. 29, 2019). The
wherein clauses in Allergan Sales related to (1) the effectiveness of an
administered glaucoma or ocular hypertension therapeutic formulation given
twice daily as compared to another therapeutic formulation given three times
daily and (2) the reduction of adverse events. On their face, such wherein
clauses share some similarities with that of the present claims because all
appear to merely recite some intrinsic functionality or intended result of a
claimed administration step. Moreover, in Allergan Sales, as here, the patent
applicant (cum-patent owner) argued during prosecution that the wherein
clauses were limitations that distinguished over the prior art. See id. at *4.
However, we find the current case distinguishable from Allergan Sales.
First, in Allergan Sales, the characteristics of the wherein clauses were
argued during prosecution to be “unexpected results” that was evidence of
non-obviousness. Id. Second, the Examiner in the application that would
become the patent-in-suit in Allergan Sales “explicitly relied on the
‘wherein’ clauses in explaining why the claims of the Patents-in-Suit were
‘novel and non-obvious over the prior art,’” meaning the evidence of
unexpected results was persuasive of patentability. Id. These facts were
important to the Federal Circuit’s affirmance in Allergan Sales. Id. at *4–
*5. Here, such facts are not present. Here, Appellant has not presented
persuasive evidence that the claimed increase in hatchability of a treated egg
following a challenge with Escherichia coli would have been an unexpected
result as compared to the closest prior art. It follows that, here, the
Examiner has not relied upon such evidence to find the claims non-obvious.
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In fact, based on her review of the Specification, here, the Examiner
determined that Appellant’s claimed invention and its activation of an innate
immune response in embryonic chicks, which results in potentially
improving hatchability if eggs are challenged with E. coli, was not
unexpected. See Answer 9–14.
OBVIOUSNESS ANALYSIS
“The combination of familiar elements [or steps] 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). The
reason or motivation to modify the reference may often suggest what the
inventor has done, but for a different purpose or to solve a different problem;
it is not necessary that the prior art suggest the combination to achieve the
same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441
F.3d 977, 988 (Fed. Cir. 2006). “[T]he test of obviousness is not express
suggestion of the claimed invention in any or all of the references[,] but
rather what the references taken collectively would suggest to those of
ordinary skill in the art presumed to be familiar with them.” In re Rosselet,
347 F.2d 847, 851 (CCPA 1965) (emphasis in original). “[T]he analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR,
550 U.S. at 418.
Where . . . the claimed and prior art products are identical or
substantially identical . . . the PTO can require an applicant to
prove that the prior art products do not necessarily or inherently
possess the characteristics of his claimed product. Whether the
rejection is based on ‘inherency’ under 35 U.S.C. § 102, on
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‘prima facie obviousness’ under 35 U.S.C. § 103, jointly or
alternatively, the burden of proof is the same, and its fairness is
evidenced by the PTO’s inability to manufacture products or to
obtain and compare prior art products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations and footnote
omitted). “It is a general rule that merely discovering and claiming a new
benefit of an old process cannot render the process again patentable.” In re
Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990).
With these standards in mind and in view of our claim interpretation
above, we address the Examiner’s rejections and Appellant’s arguments
there-over.
The Examiner determined that claims would have been obvious over
the Gomis, Dow, and Zaks combination. See Final Action 2–5, and Answer
3–15 (collectively citing Gomis 813 (abstract), 816, 820, 821; Dow 1
(abstract), 3–4; Zaks 7335 (abstract), 7336, 7341). To summarize, it is the
Examiner’s position that Gomis teaches the stimulation of the innate
immune system (non-specific) of unhatched chickens to protect against E.
coli infection (we note, Gomis discloses E. coli can infect chick in ovo) by
administering in ovo a composition of CpG ODN, which is a non-coding (for
immunogen) nucleic acid molecule; while Gomis teaches its in ovo dosage
was 50 µg, it also taught a 10 µg dosage (provided intramuscularly) was
similarly effective, which suggests the claimed dosage. See FF1–FF4. The
Examiner notes that Gomis does not disclose that CpG ODN is administered
with a cationic liposome, but takes the position that it would have been
obvious for the skilled artisan to look to Dow for such a teaching because it
disclosed that administering a cationic liposome-nucleic acid molecule
complex (and cationic liposome-DNA plasmid complex) provided
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significant advantages in therapeutic immune-stimulation. See FF5–FF6.
The Examiner also notes that Gomis does not disclose that an immune-
stimulating nucleic acid molecule can be a plasmid DNA, but takes the
position that it would have been obvious for the skilled artisan to look to
Zaks for such a teaching because Zaks discloses that liposomes can be
complexed with both plasmid DNA and CpG ODN to elicit enhanced
immune response. See FF7. We discern no error in the Examiner’s
determinations and, as noted above, adopt the Examiner’s findings of fact
and rationale on obviousness.
Appellant argues that the Examiner’s rejection relies on an inherency
theory that the claimed increased hatchability after an egg’s challenge with
E. coli would result from Gomis’s disclosed in ovo CpG ODN
administration, but that it would have been impossible for the skilled artisan
to determine whether such a result would necessarily occur. Appeal Br. 4–5.
Appellant argues Gomis’s composition is not the same as that claimed (it
does not include a liposome), so there can be no basis for such a
determination. Id. Appellant also argues that Gomis did not disclose
challenging eggs with E. coli, but only hatched chicks, which also forecloses
a determination under an inherency theory. Id. at 6–11. In a related
argument, Appellant contends the skilled artisan would not have had a
reasonable expectation of successfully inoculating chicken embryos to result
in increased hatchability. Id. at 11.
These arguments are not persuasive. As discussed above, the claim
language in the preamble and in the wherein clause relating to increased
hatchability after E. coli challenge does not limit the claims. Therefore,
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Gomis’s lack of teaching focusing on such a result is not determinative.
Gomis discloses the same administration timing, using a nucleic acid
molecule, to the same organism as claimed. Gomis also suggests the
claimed dosage to be administered and teaches that it elicited
immunoprotection against E. coli infection. Dow and Zaks would have been
obvious to combine with Gomis as they are related to the same general
treatment and intended results as Gomis, and they teach or suggest
complexing a plasmid DNA with a cationic liposome, as claimed. Based on
the disclosures of Gomis, Dow, and Zaks, a skilled artisan would have
reasonably expected to successfully administer such a therapeutic plasmid
DNA-cationic liposome complex to chickens in ova and that such
administration would protect the embryonic chicks from E. coli. by
stimulating an immunoprotective response against infection by the bacteria.
See supra Findings of Fact; see also Best, 562 F.2d at 1255; and Woodruff,
919 F.2d at 1578.
Regarding claim 35, specifically, Appellant notes it requires using a
plasmid DNA as a nucleic acid in the administered composition, but
reiterates the aforementioned argument that the cited prior art does not
discuss pre-hatch innate immunity for increasing hatchability. Id. at 12.
This argument is not persuasive. For the reasons discussed above
regarding claim 27, claim 35 also would have been obvious over the
combination of Gomis, Dow, and Zaks. As noted above, the prior art
combination made it obvious to use a plasmid DNA as the nucleic acid
molecule of claim 27, as required by claim 35. Furthermore, as noted above,
the claims’ recited increased hatchability is not a limitation.
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In the Reply Brief, Appellant argues that Gomis does not teach
cationic liposomes and that this component is an important component of the
claims. Reply Br. 3.
This argument is not persuasive. The rejection is over the
combination of Gomis, Dow, and Zaks, not Gomis individually. “Non-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references. . . . [The reference] must be read, not in isolation, but for what it
fairly teaches in combination with the prior art as a whole.” In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Here, it would have been
obvious to combine Gomis with Dow and Zaks and both Dow and Zaks
teach or suggest the advantages of complexing a nucleic acid molecule or
plasmid DNA with a cationic liposome to stimulate an immunoresponse,
which would have rendered the claimed invention obvious.
As noted above, we agree with and adopt the Examiner’s findings of
fact and rationale regarding the obviousness of the claims. We discern no
error in the Examiner’s determinations, which we find present a prima facie
case for the claims’ obviousness over the cited prior art combination. We
have considered Appellant’s arguments over the rejections in their entirety,
but find them unpersuasive.
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SUMMARY
The obviousness rejection of claims 34–40 and 49 under 35 U.S.C.
§ 103(a) is affirmed.
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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED