Bitop AG

Patent Trials and Appeals Board

Jul 23, 2021

2020006526 (P.T.A.B. Jul. 23, 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.
14/980,374 12/28/2015 Rene Tolba BITA0101PUSA2 5352
62836 7590 07/23/2021
Brooks Kushman P.C. / BERLINER & ASSOCIATES
1000 Town Center, 22nd Floor
22nd Floor
Southfield, MI 48075
EXAMINER
BAEK, BONG-SOOK
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
07/23/2021 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):
docketing@brookskushman.com
lwerk@brookskushman.com
nwhitlock@brookskushman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte RENE TOLBA, GERHILD van ECHTEN-DECKERT,
GEORG LENTZEN, and ANDREAS BILSTEIN
________________

Appeal 2020-006526
Application 14/980,374
Technology Center 1600
________________

Before DONALD E. ADAMS, TIMOTHY G. MAJORS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

MAJORS, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a method of treatment of a patient suffering from postoperative
inflammatory stress and pain. The claims have been rejected for
obviousness under 35 U.S.C. § 103. We have jurisdiction under
35 U.S.C. § 6.
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42(a). Appellant identifies Bitop AG as the real party-in-
interest. Appeal Br. 3.
Appeal 2020-006526
Application 14/980,374

2
STATEMENT OF THE CASE
“The invention relates to tetrahydropyrimidines and their use in the
prevention and treatment of postoperative inflammatory stresses and pain.”
Spec. ¶ 2. The Specification notes that tetrahydropyrimidine derivatives
(e.g., ectoine and hydroxyectoine) are “synthesized from extremophilic
microorganisms under stress conditions and serve the purpose of stabilizing
the cell structures of these microorganisms under extreme thermal, chemical
and physical conditions.” Id. ¶ 4. As further background, the Specification
explains, ectoine is “known to have a stabilizing effect on protein and
nucleic acid structures with said effect being conducive to the stabilization
of biological material and pharmaceutical preparations.” Id. ¶ 5.
The Specification discloses that “[p]roteolysis is associated with the
healing process of a wound and ends with the disappearance of damaged
tissue.” Id. ¶ 8. According to the Specification, proteolysis “does not play a
role where there is long lasting stress and pain.” Id. (“Long lasting means
that the negative effects outlast the healing process for a long time, in some
cases permanently.”).
The Specification, in the Summary of Invention, discloses that “[t]he
invention relates to a method of treatment of postoperative inflammatory
stress and pain in a class of patients suffering from postoperative
inflammatory stress that doesn’t suffer from uncontrolled proteolysis,”
comprising administering ectoine or hydroxyectoine. Id. ¶ 10. “More
particularly, a method of treatment is provided for a patient suffering from
postoperative inflammatory stress and pain caused by mechanical impact
exerted on portions of the body . . . wherein the inflammatory stress and pain
of the operation outlast the healing of damaged tissue.” Id. (“The stress and
Appeal 2020-006526
Application 14/980,374

3
pain related to, or caused by, uncontrolled proteolysis, ends with
disappearance of damaged tissue; it does not outlast the healing of damaged
tissue.”).
Claims 1–11 are on appeal. Claim 1 is the only independent claim; it
is illustrative and is reproduced below:
1. A method of treatment of a patient suffering from
postoperative inflammatory stress and pain caused by
mechanical impact exerted on portions of the body of the patient
that caused damaged tissue and proteolysis associated with the
healing process of the damaged tissue, the patient having
outlasting inflammatory stress and pain of due to the operation
at a stage after the damaged tissue has been healed and said
proteolysis has ended, comprising administering a
tetrahydropyrimidine selected from ectoine and/or
hydroxyectoine to the patient.
Appeal Br. 14 (emphasis added to key limitation in dispute).
Appellant seeks review of the Examiner’s rejection of claims 1–11
under 35 U.S.C. § 103 as obvious over the combination of Tolba2 and
Unfried ’299 (or its English-language equivalent, Unfried ’869),3 as further
evidenced by Gutierrez.4 Final Act. 7–11.5

2 Tolba et al., US 2011/0269784 A1, published Nov. 3, 2011 (“Tolba”).
This publication corresponds to US Patent Application No. 12/863,832,
which was filed as the national stage entry of a PCT application filed
January 30, 2009.
3 Unfried et al., WO 2013/034299 A1, published Mar. 14, 2013 (in German);
Unfried et al., US 2014/0315869 A1, published Oct. 23, 2014. We refer to
Unfried ’299 and Unfried ’869 herein, collectively, as “Unfried” and our
citations are to the English-language version of Unfried ’869.
4 Carolyn Gutierrez, 23 Healing Postsurgery Wounds 4, For The Record, 24
(2011).
5 This citation refers to the Final Rejection dated March 21, 2019 (“Final
Act.”). We also refer herein to the Examiner’s Answer on Appeal dated
Appeal 2020-006526
Application 14/980,374

4
I. Priority of the Appealed Claims
A threshold issue in dispute is the priority date of the appealed claims.
Final Act. 2–6; Appeal Br. 9–10. This application (US Patent Application
No. 14/980,374) was filed December 28, 2015, as a continuation-in-part
(“CIP”) of US Patent Application No. 13/707,259 (“the ’259 Application”)6
filed December 6, 2012, which is a continuation of US Patent Application
No. 12/862,832 (i.e., the application which published as US 2011/0269784,
the asserted Tolba reference).
Appellant and Examiner dispute the priority date of the appealed
claims, which determines whether Tolba is prior art. Final Act. 2–6; Ans. 8–
11. If those claims are entitled to priority of the ’259 Application (and, by
extension, Tolba7), Tolba is removed as a prior art reference for the § 103
rejection. Alternatively, if there is insufficient written description support in
the ’259 Application for the pending claims, as argued by the Examiner,
those claims are entitled to priority no earlier than the December 28, 2015,
filing of the CIP application and Tolba is prior art.
“It is elementary patent law that a patent application is entitled to the
benefit of the filing date of an earlier filed application only if the disclosure

June 18, 2020 (“Ans.” or “Answer”).
6 See Tolba et al., US 2014/0163053, published June 12, 2014. We cite the
disclosures in this published version of the ’259 Application.
7 Although neither Appellant nor Examiner address expressly, we treat the
’259 Application and Tolba as having substantially identical disclosures for
purposes of resolving the priority dispute. Lockwood v. Am. Airlines, Inc.,
107 F.3d 1565, 1571 (Fed. Cir. 1997) (explaining that, to claim “the benefit
of the filing date of an earlier application under 35 U.S.C. § 120, each
application in the chain leading back to the earlier application must comply
with the written description requirement of 35 U.S.C. § 112”).
Appeal 2020-006526
Application 14/980,374

5
of the earlier application provides support for the claims of the later
application, as required by 35 U.S.C. § 112.” In re Chu, 66 F.3d 292, 297
(Fed. Cir. 1995); see also Augustine Med., Inc. v. Gaymar Indus., Inc., 181
F.3d 1291, 1302–03 (Fed. Cir. 1999) (“Different claims of [a CIP]
application may therefore receive different effective filing dates. . . . Subject
matter that arises for the first time in [a] CIP application does not receive the
benefit of the filing date of the parent application.”).
To satisfy the written description requirement, “the missing
descriptive matter must necessarily be present in the [original] application’s
specification such that one skilled in the art would recognize such a
disclosure.” Tronzo v. Biomet, Inc., 156 F.3d 1154, 1159 (Fed. Cir. 1998).
“Entitlement to a filing date [for priority] does not extend to subject matter
which is not disclosed, but would be obvious over what is expressly
disclosed.” PowerOasis, Inc. v. T-Mobile USA, Inc., 522 F.3d 1299, 1306
(Fed. Cir. 2008) (quoting Lockwood v. Am. Airlines, Inc., 107 F.3d 1565,
1571–72 (Fed. Cir. 1997)).
The Examiner finds that the present claims require treating a certain
type of patient: one with “outlasting inflammatory stress and pain due to the
operation after the damaged [tissue] has been healed and . . . proteolysis has
ended.” Final Act. 2 (emphasis omitted). The Examiner further finds that
treating this sort of patient—those treated after tissue healing and proteolysis
ended—“was not disclosed in the parent applications.” Id. (“The parent case
does not disclose the healing status of damaged tissue and the absence of
proteolysis associated with the healing process.”). To the contrary, the
Examiner finds, the ’259 Application describes treatment of postoperative
inflammatory stress and pain that starts immediately after the surgical
Appeal 2020-006526
Application 14/980,374

6
intervention. Id. at 4. As the Examiner explains, such treatment “may or
may not continue after healing and proteolysis ended,” but there “is no
evidence that the treatment in the ‘259 application continues even after
healing and proteolysis ended.” Id. at 4 (finding “no information [in the
’259 Application] as to the treatment of identifying and selecting the claimed
subset of patient population,” whose “damaged tissue due to the operation
has healed and proteolysis associated with the healing process . . . has
ended.”).
Appellant argues that, “in the Serial No. 14/707259 application, it is
unrealistic to assume that the treatment stopped just after healing and
proteolysis ended.” Appeal Br. 9. Rather, Appellant contends, “[i]t is
inherent and necessary” in the ’259 Application “that treatment occurred at a
stage where healing and proteolysis ended.” Id. (citing Yeda Research and
Dev. Co., v. Abbott GmbH & Co., 837 F.3d 1341 (Fed. Cir. 2016) for the
proposition that “undisclosed yet inherent properties” can serve as adequate
descriptive support of such properties)).
On this record, the preponderance of the evidence supports the
Examiner’s determination on priority. Appellant cites no disclosure in the
’259 Application that sufficiently describes identifying or treating the
narrower patient population required in the now-claimed method. Indeed, it
appears that all the disclosure about proteolysis and treating patients later—
after healing and proteolysis ended—was added expressly in the CIP
application. Compare Spec. ¶¶ 8–10 (Background and Summary of
Invention), with ’259 Application ¶ 7 (Summary of Invention).
Unable to cite any actual descriptive support in the ’259 Application,
Appellant is left arguing inherency. But Appellant provides no evidence to
Appeal 2020-006526
Application 14/980,374

7
back its argument that treating the now-claimed subset of patients is
necessarily present, and thus inherent, in the ’259 Application’s disclosure.
In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) (“Attorney’s argument in
a brief cannot take the place of evidence.”).
Insofar as Appellant tries to turn the prior art rejection around on the
Examiner, that argument misinterprets the rejection as being based on
inherency. Appeal Br. 9–10. The Examiner never asserted that treating the
newly recited subset of patients is inherent in the ’259 Application (or
Tolba). Quite the opposite, the Examiner explains that the method of the
’259 Application “may or may not” have been continued to treat patients
later in the healing process, even after proteolysis ended. Final Act. 4.
Inherency is not, however “established by probabilities or possibilities.”
Scaltech Inc. v. Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999)
(“The mere fact that a certain thing may result from a given set of
circumstances is not sufficient to establish inherency.”). And the Examiner
was clear: the “conclusion of obviousness [here] is not based on inherency,
but is based on the combined teachings of cited prior art references.” Final
Act. 11. That it would have been obvious over Tolba and the other
references to treat a post-proteolysis subset of patients, as the Examiner
concluded and as we address below, does not present any inconsistency with
the Examiner’s finding on priority. PowerOasis, 522 F.3d at 1310
(“Obviousness simply is not enough; the subject matter must be disclosed to
establish possession.”).
For the reasons above, we agree with the Examiner’s determination on
priority. The present claims are not entitled to the priority filing dates of the
’259 Application or Tolba. Tolba is, thus, prior art.
Appeal 2020-006526
Application 14/980,374

8
II. Obviousness over Tolba, Unfried, and Gutierrez
The Examiner concludes that claims 1–11 would have been obvious
over Tolba and Unfried, as further evidenced by Gutierrez. Final Act. 7–10.
Appellant’s argument for this rejection is addressed to the claims as a group.
We focus here on claim 1, and the other claims stand or fall with claim 1.
See 37 C.F.R. § 41.37(c)(iv).
The Examiner finds that Tolba teaches the use of ectoine and
hydroxyectoine for treating a patient suffering from postoperative
inflammatory stress and pain. Final Act. 7 (citing, inter alia, Tolba, Abstr.,
¶¶ 10, 18, and claims 1–4). The Examiner further finds that Tolba teaches or
suggests the use of the above compounds for postoperative treatment of
inflammation and pain in patients that have undergone procedures (e.g.,
endoscopic interventions in the abdomen), and at dosages and routes of
administration that overlap with the limitations of the claims. Id.; see also
Tolba ¶¶ 10, 15, 16.
The Examiner finds, however, that Tolba does not disclose treating a
patient with “outlasting inflammatory stress and pain (chronic inflammation)
due to the operation after the damaged tissue due to the operation has been
healed and proteolysis associated with the healing process of the damaged
tissue has ended” as required by claim 1. Final Act. 8. The Examiner, thus,
turns to Unfried. According to the Examiner, Unfried teaches the use of
ectoine and hydroxyectoine for suppression of anti-apoptotic signals to
neutrophils and other cells responsible for inflammation and delayed
apoptosis. Id. The Examiner finds that Unfried teaches that accumulation of
neutrophils in an infected area is a major component of inflammation and
long-lasting apoptotic delay. Unfried ¶ 7. Moreover, the Examiner finds,
Appeal 2020-006526
Application 14/980,374

9
Unfried teaches that ectoine is useful for treating “chronic inflammation”
and that the “diminishing of the amount of neutrophils as well as a lowering
of the cinc-1 level were . . . observed when ectoine had been administered
repeatedly after an inflammation reaction had been triggered off several
times, which even underlines its usefulness for the treatment of chronic
inflammatory phenomena.” Final Act. 8–9; Unfried ¶¶ 8, 9, 12.
Citing Gutierrez as evidence, the Examiner explains that the basic
biological response to a wound was known and involves three stages: the
first, “inflammatory phase”; a second “proliferative phase” when new tissue
is formed; and a third, “remodeling phase” in which apoptosis (cell death)
occurs, leading to fibrosis and scarring. Final Act. 9; see generally
Gutierrez. According to the Examiner, the skilled artisan would have
recognized that apoptosis of neutrophils and other inflammatory cells, such
as discussed in Unfried, occurs after the second stage where damaged tissue
is healed and proteolysis has ended. Final Act. 9.
Continuing, the Examiner concludes that it would have been obvious
to use ectoine-containing compositions of Tolba to treat a patient with
outlasting inflammatory stress and pain post-proteolysis as recited in
claim 1. In support, the Examiner cites Unfried’s teaching that ectoine is
“useful for treating chronic inflammatory phenomena even after the
inflammatory reaction had been triggered off due to its suppressive effects
on anti-apoptotic signals.” Id. at 9–10. Furthermore, the Examiner reasons,
the skilled artisan would have recognized from Unfried’s and Gutierrez’s
teachings that “chronic inflammation can be developed after surgical
intervention even after the damaged tissue has been healed during the second
stage and proteolysis associated with the healing process of the damaged
Appeal 2020-006526
Application 14/980,374

10
tissue has been ended.” Id. at 10. So, the Examiner reasons, a skilled artisan
would have been motivated to administer ectoine to patients for treatment of
chronic inflammatory phenomena even after healing and proteolysis. Id.
Appellant makes the following arguments in response. First,
Appellant argues that Unfried teaches use of ectoine in the first
inflammation stage, not any later stage where proteolysis has ended, and
that, by teaching use in an inflammatory stage, Unfried teaches away from
the invention. Appeal Br. 7–8. Second, Appellant argues that the Examiner
is relying on conclusory reasoning and hindsight to arrive at the claimed
method. Id. at 10–11.
On this record, the preponderance of the evidence weighs in the
Examiner’s favor. As determined by the Examiner, Tolba teaches giving
ectoine to patients for treatment of postoperative inflammatory stresses and
pain. See Tolba, Abstr., ¶¶ 10, 15, 16, 18, claims 1–4. Tolba does not,
however, expressly teach administering ectoine in subjects experiencing
chronic (i.e., outlasting) postoperative inflammation and pain at a stage after
tissue has healed and proteolysis ended, as recited in claim 1. We are,
however, persuaded by the Examiner’s reasoning that, because Unfried
teaches a use of ectoine to treat chronic inflammation and to suppress anti-
apoptotic signaling, including a repeated administration even after
inflammation reactions are “triggered off” several times, a skilled artisan
would have been motivated to administer Tolba’s compositions to long-
term, chronic sufferers of postoperative inflammation and pain phenomena.
We also agree with the Examiner that, as further evidenced by Gutierrez and
Unfried, it would have been obvious to treat chronic sufferers in the later
stages of wound recovery (i.e., post-proteolysis) where apoptosis and
Appeal 2020-006526
Application 14/980,374

11
scarring occurs. Appellant provides no persuasive evidence to the contrary
on this record.
Appellant’s teaching away argument is unavailing. Even if Unfried
teaches administering ectoine during an inflammation stage to address
inflammation caused by white blood cells or other inflammatory mediators,
that does not mean that Unfried discredits ectoine’s use after such
inflammation ends or at another stage. In re Fulton, 391 F.3d 1195, 1201
(Fed. Cir. 2004) (holding there is no teaching away when the art suggests
alternatives and “does not criticize, discredit, or otherwise discourage the
solution claimed.”). The present claims do not exclude administration in a
first inflammatory stage—a persistent or continuing administration from a
first through third wound recovery phase would, for example, meet the claim
language. And, as explained above, we find that the preponderance of the
evidence on this record supports the Examiner’s position that Unfried
(especially combined with Tolba and Gutierrez) teaches more, including a
repeated administration to treat against chronic inflammatory phenomena
and to limit anti-apoptotic signaling, even after primary inflammation has
been “triggered off.” Unfried ¶ 12;8 Ans. 5–8, 12.
For similar reasons, we reject Appellant’s argument that the
Examiner’s rejection is conclusory and reliant on hindsight. The Examiner’s
reasoning is based on the prior art’s combined teachings, assessed from the
perspective of the skilled artisan, as explained above. See Ans. 12.

8 Appellant’s brief does not address some of the key disclosures of Unfried
cited by Examiner, including Unfried’s paragraph 12.
Appeal 2020-006526
Application 14/980,374

12
Accordingly, we determine that the preponderance of the evidence
supports the Examiner’s conclusion that claims 1–11 would have been
obvious over Tolba and Unfried, as further evidenced by Gutierrez.
CONCLUSION
For the reasons explained above, the preponderance of the evidence
supports the Examiner’s rejections on appeal.
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–11 103 Bromley, Unfried,
Gutierrez
1–11

TIME PERIOD FOR RESPONSE
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