Ex Parte Badalemente et al

Patent Trial and Appeal Board

Apr 4, 2016

11703269 (P.T.A.B. Apr. 4, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111703,269 0210712007
138209 7590 04/06/2016
Elmore Patent Law Group, P.C.
Carolyn S. Elmore
484 Groton Road
Westford, MA 01886
FIRST NAMED INVENTOR
Marie A. Badalemente
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.
4024.3003 USl 9916
EXAMINER
ROBINSON, HOPE A
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
04/06/2016 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):
docketing@elmorepatents.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARIE A. BADALEMENTE and ALEXANDER B. DAGUM
Appeal2014-000593
Application 11/703,269 1
Technology Center 1600
Before LORA M. GREEN, JEFFREY N. FREDMAN, 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 directed to methods of treating cellulite with purified collagenase.
The Examiner rejects claims 1, 4, 8-10, 12-14, and 18-21under35 U.S.C.
§§ 112, second paragraph, and 103(a). We have jurisdiction under 35
U.S.C. § 6(b ).
We affirm.
1 According to Appellants, the real party in interest is The Research
Foundation of State University of New York. App. Br. at 1.
Appeal2014-000593
Application 11/703,269
STATEMENT OF THE CASE
Claims 1, 4, 8-10, 12-14, and 18-21 of U.S. Patent Application No.
11/703,2692 are on appeal. These claims can be found in the Claims
Appendix of the Appeal Brief. Independent claim 1 reads as follows:
1. A method of treating cellulite in a subject in need of such
treatment, the method comprising
administering an effective amount of purified collagenase I and
II obtained from Clostridium histolyticum to the collagenous
septa network of cellulite,
wherein the purified collagenase I and II is substantially free of
other enzymes, and
wherein the purified collagenase I and II is administered by
injection at a dose comprising at least about 1500 SRC units,
applied in one or more injections.
App. Br. at 29, Claims Appendix (line breaks added). Independent claim 8
reads as follows:
8. A method of treating cellulite in a subject in need of such
treatment, the method comprising
administering an effective amount of purified collagenase I and
II obtained from Clostridium histolyticum to the collagenous
septa network of cellulite,
wherein the purified collagenase I and II is substantially free of
other enzymes and
wherein the purified collagenase I and II is administered by
injection at a dose comprising at least about 10000 ABC units,
applied in one or more injections.
2 All references herein to the "Specification" or "Spec." are to the published
version of the appealed application (Pub. No. 2007/0224184 Al, published
Sept. 27, 2007).
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Application 11/703,269
Id. 29-30 (line breaks added).
The following grounds of rejection are on appeal:
A. Claims 1, 4, 8-10, 12-14, and 18-21under35 U.S.C. § 112,
second paragraph, as being indefinite (Final Action 2);
B. Claims 1, 4, 8-10, 12-14, and 18-21under35 U.S.C. §103(a)
as being unpatentable over Pinnell, Dwulet, and Wegman (Final Action 4);
and
C. Claims 1, 4, 8-10, 12-14, and 18-21under35 U.S.C. §103(a)
as being unpatentable over Pinnell, Dwulet, and Badalemente (Final Action
7).
FINDINGS OF FACT
FF 1. Pinnell disclosed methods for preventing and treating
human/animal scaring, i.e., cicatrices, relating to collagen formations,
including cellulite and other cosmetic defects, including intra-dermal
injection(s) of effective amounts of a pharmacologically suitable solution of
highly purified collagenase produced from Clostridium histolyticum-
individually or combined with other enzymes. Pinnell Abstract; col. 1, 1.
64---col. 2, 1. 5; col. 2, 1. 61---col. 3, 1. 18; see Final Action 4--7; and see Ans.
10-19 (discussing Pinnell).
FF2. Pinnell disclosed that purified collagenase (free of
detectable non-specific protease activity) could be obtained from a
distributor (Advance Biofactures Corporation of Lynbrook, NY), that this
purified collagenase can be put into solution, and that its enzyme activity is
given in ABC units ("units"). Pinnell col. 3, 11. 22-36.
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FF3. Pinnell disclosed two examples of actual cicatrices
treatment using collagenase injections into collagenous citratrix lesions,
where multiple injections are performed over many weeks at intervals.
Pinnell col. 3, 11. 48---60; col. 4, 11. 20-28; see Final Action 4---6 (discussing
Pinnell's disclosure of Examples).
FF4. Pinnell disclosed an example of human cicatrix treatment
with multiple collagenase injections, which consisted of an initial treatment
of four injections totaling 900 (i.e., 50 + 100 + 250 + 500) units in 0.4 ml
directly into a lesion, which was repeated (after selecting an optimum
concentration of collagenase) in the same patient after one month (e.g., 4
weeks) and then again at appropriate intervals until lesion size reduction was
achieved. Pinnell col. 3, 11. 48---60; see Final Action 6 (discussing Pinnell's
Example and dosages) and Ans. 12 (discussing the additive amounts and
intervals of Pinnell's injection treatments in Example 1).
FF5. Pinnell disclosed an example of treating a human
patient's cellulite using multiple injections of collagenase combined with
hyaluranidase, repeated at intervals (2 weeks) until a desired improvement in
skin contour is achieved. Pinnell col. 4, 11. 31-39; see Ans. 11 (discussing
Pinnell Example V).
FF6. Pinnell disclosed that based on its disclosure, reasonable
experimentation by a person of ordinary skill in the art to determine how to
modify its otherwise-disclosed treatment of cicatrices should consider the
nature of the cicatrix to be treated, the concentration and type of enzymes to
be used, the amount and location and nature of the fibers to be dissolved,
and the nature of adjacent tissue. Pinnell col. 4, 11. 40-56; see Ans. 12
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(discussing how the ordinary skilled artisan would understand Pinnell and
how to modify its teachings).
FF7. Dwulet disclosed compositions for enzymatic dissociation
of extracellular tissue matrices to allow tissue remodeling. Dwulet col. 1, 11.
7-10; see Spec. i-f 10 and Ans. 16 (recognizing that Dwulet discloses
treatment of a disorder similar to the cellulite of Pinnell).
FF8. Dwulet disclosed that crude collagenase can be derived
from Clostridium histolyticum and crude collagenase contains a mixture of
protease enzymes and non-protease components. Dwulet col. 1, 11. 29-37.
FF9. Dwulet disclosed that crude collagenase showed extreme
variations in components and performed unpredictably in tissue dissociation
protocols. Id. col. 1, 11. 38--43. Dwulet disclosed that skilled practitioners
recognized the importance of overcoming these disadvantages of crude
collagenase by using pure collagenase compositions of collagenase I and
collagenase II (with other neutral proteases). Id. at col. 1, 1. 62---col. 2, 1. 5;
see Final Action 6 (discussing Dwulet) and Ans. 14--19 (discussing Dwulet
and its combination with other references).
FFlO. Wegman disclosed treatment of Dupuytren's disease in
humans by injecting collagenase (only) into the fibrous Dupuytren's cord in
the hand (Dupuytren's disease, like cellulite, was known to be associated
with collagen cords or plaques). Wegman col. 1, 11. 14--15, 61---67; Spec.
i-f 1 O; see Ans. 16 (recognizing that Wegman discloses treatment of a
disorder similar to the cellulite of Pinnell).
FFl 1. Wegman disclosed treating collagen cords using
injections of about 8,000 ABC units to about 15,000 ABC units. Wegman
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Application 11/703,269
col. 2, 11. 44--57; see Final Action. 7 (identifying that "Wegman teaches
administration of the dosage of 1500 SRC").
FF12. Wegman disclosed "excellent clinical results" by treating
Dupuytren's chord with three injections of purified collagenase derived from
Clostridium histolyticum at 10,000 ABC units in 0.5 or 0.25 ml diluent in
different places about 2 mm apart. Wegman col. 4, 11. 38-51.
FF13. Badalemente disclosed injecting collagenase into
collagenous adhesions in the shoulder to treat or prevent adhesive capsulitis
(or frozen shoulder; adhesive capsulitis, like cellulite, was known to be
associated with collagen cords or plaques). Badalemente i-f 4; Spec. i-f 1 O; see
Ans. 29 (recognizing that Badalemente discloses treatment of a disorder
similar to the cellulite of Pinnell).
FF14. Badalemente disclosed treating adhesive capsulitis
plaques by injecting collagenase I and collagenase II, with a specific activity
of at least about 1500 SRC units/mg., at a volume up to 0.50 ml at a time,
repeated at 4 to 6 week intervals (for, e.g., three treatments). Badalemente
i-fi-14, 13, 16, 22, 26 (Table 1); see Final Action 9 (discussing Badalemente's
disclosure of dosages and repeated treatments as claimed).
FF15. In the present case, the person of ordinary skill in the art
would include a medical practitioner with experience in administering and
dosing pharmaceutical agents. App. Br. 6; see Ans. 12, 15, 18 (discussing
identity and abilities of person of ordinary skill in the art).
FF16. The Specification defines an SRC unit as follows: "[ o ]ne
SRC unit will solubilize rat tail collagen into ninhydrin reaction material
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Application 11/703,269
equivalent to 1 nanomole of leucine per minute, at 25 degrees, C, pH 7.4."
Spec. i122.
FF17. The Specification defines one net ABC unit as follows:
"[ o ]ne net ABC unit of collagenase will solubilize ninhydrin reactive
material equivalent to 1.09 nanomoles of leucine per minute. One SRC unit
equals approximately 6.3 ABC units." Spec. i122.
FF18. Based on the Specification's definitions:
1500 SRC units = approximately 9450 ABC units; and
10000 ABC units= approximately 1587 SRC units.
Spec. i122.
FF19. Each of the Examiner-cited references define the use
collagenase enzyme in terms of enzyme activity units, be those the "unit[ s]
of activity" of Pinnell (at col. 3, 11. 31-34 ), "Wunsch unit[ s ]" of Dwulet (col.
4, 11. 46-48), "ABC units" of Wegman (col. 2, 11. 7-57), or "SRC units" of
Badalemente (i-f 13). These are conventional terms of art that would have
been readily understood by the person of ordinary skill in the art. See Reply
Br. 5---6.
DISCUSSION
A. The rejection of claims 1, 4, 8-10, 12-14, and 18-21under35
U.S.C. § 112, second paragraph, as being indefinite
The Examiner rejects the above-referenced claims because
independent claims 1 and 8 recite "a dose comprising at least about 1500
SRC units" and "a dose comprising at least about 10,000 ABC units,"
respectively, and the Specification does not expressly define what is
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Application 11/703,269
encompassed by the term "at least about." Final Action 3; App. Br. 29-30
(emphasis added).
The question is whether the Examiner established by a preponderance
of the evidence of record that the skilled artisan would not understand the
metes and bounds of the claims on the basis that they use the term "at least
about." We agree with Appellants that the Examiner has not established that
the ordinary artisan would not understand the metes and bounds of the
limitation(s) "at least about" within the context of the claims. Therefore, we
reverse the rejection.
"Although it is rarely feasible to attach a precise limit to 'about,' the
usage can usually be understood in light of the technology embodied in the
invention." Modine Manufacturing Co. v. US. ITC, 75 F.3d 1545, 1554
(Fed. Cir. 1996). That is the case here, where as argued by the Appellants,
the person of ordinary skill in the art (i.e., a medical practitioner with
experience in administering and dosing pharmaceutical agents) would
understand the terms "SCR units" and "ABC units" as they are used in the
claims. App. Br. 6. These terms would be conventional to such a skilled
artisan, who would routinely use this terminology to refer to a dose or
amount of enzyme. Reply Br. 5; see also FF19 (above, identifying that each
cited reference uses these or similar terms).
We are persuaded by Appellants' argument that the recitation of an
amount of at least about 1500 SRC units or an amount of at least about
10,000 ABC units would be understood by the skilled artisan as indicating a
dose of collagenase of about 1500 SRC units or more and a dose of
collagenase of about 10,000 ABC units or more, respectively. App. Br. 6.
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For these reasons, the rejection of claims 1, 4, 8-10, 12-14, and 18-
21under35 U.S.C. § 112, second paragraph, is reversed.
B. and C. The rejections of claims 1, 4, 8-10, 12-14, and
18-21under35 U.S.C. §103(a) as being unpatentable over Pinnell,
Dwulet, and Wegman/Badalemente
The rejections of the claims under 35 U.S.C. § 103(a) rely on the same
prior art and arguments, with the exception that the third reference in each of
the two rejections is alternatively Wegman or Badalemente, but used to the
same purpose in each rejection. We address both rejections at once.
Claims 1 and 8
The Examiner determined that Pinnell disclosed much of the subject
matter claimed, including a method of treating cellulite in general (Pinnell
Abstract; col. 2, 1. 61---col. 3, 1. 18), administering an effective amount of
purified collagenase (obtained from Clostridium histolyticum; see Pinnell
col. 1, 11. 64---col. 2, 1. 5; col. 3, 11., 22-36) to the collagenous septa network
of cellulite (Pinnell Abstract; col. 2, 1. 61---col. 3, 1. 18), that the purified
collagenase was substantially free of other enzymes (Pinnell col. 2, 11. 2-5;
col. 3, 11. 22-36), and that the purified collagenase was administered by
injection (Pinnell col. 3, 11. 48---60; col. 4, 11. 20-28, 31-39}-as per
independent claims 1and8. See Final Action 4--10; Ans. 10-31.
The Examiner determined that Pinnell lacked a disclosure that its
purified collagenase was collagenase I and collagenase II, as recited by
independent claims 1 and 8, and for this the Examiner determined that
Dwulet's disclosure of these more specific collagenases (I and II obtained
from Clostridium hisolyticum) would have been obvious to combine with
Pinnell. Final Action 6; Ans. 14.
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Appellants argued that the combination of Dwulet with Pinnell was
not appropriate because the two dealt with different diseases. We disagree.
As the Examiner pointed out and as discussed in the Specification,
each reference addresses a collagen-based ailment and disclosed using
collagenase to treat such ailment. The Specification itself states,
"[ c ]ollagenase injections have been proposed for the treatment of diseases
such as Dupuytren's disease, adhesive capsulitis and Peyronie's disease.
These diseases are all associated with collagen cords or plaques." See Spec.
i-f 10 (emphasis added) and Ans. 16. The Background section of the
Specification discusses the well-known link between cellulite and female
thigh and buttocks connective tissue, i.e., collagen. Spec. i-fi-13---6. This
establishes a clear, known link between these diseases. Ans. 16, 17, 29.
Whether a reference constitutes analogous-art (so as to be appropriate
for an obviousness rejection) depends upon whether it is in the field of the
applicant's endeavor or is reasonably pertinent to the problem with which
the inventor was concerned. In re Kahn, 441F.3d977, 987-88 (Fed. Cir.
2006). The Federal Circuit encouraged the use of common sense in deciding
in which fields a person of ordinary skill would reasonably be expected to
look for a solution to the problem facing the inventor. Id. at 988 (citing In re
Wood, 599 F.2d 1032, 1036 (CCPA 1979)). Here, we find that Dwulet and
Pinnell are analogous art and are combinable as they are each in the field of
the appealed claims' endeavor, which is treating collagen-based medical
conditions (with collagenase ). Moreover, Dwulet, on its face is pertinent
because it identifies strong motivation to make the combination with Pinnell,
specifically indicating that its collagenase I and II are more predictable to
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use in tissue dissociation protocols than Pinnell's more generic, purified
collagenase. See FF8-9.
The Appellants also argued (App. Br. 11-12) that Dwulet and Pinnell,
alone or in combination, failed to teach collagenase "substantially free of
other enzymes." Appellants point to the fact that Dwulet discloses a
treatment where collagenase I and collagenase II are used in combination
with endoprotease. App. Br. 12. Appellants overlook the fact that Pinnell
disclosed (see, e.g., Pinnell Abstract) using purified collagenase individually
to treat cellulite and that the Examiner cited Dwulet for the express purpose
of modifying Pinnell to replace purified collagenase with purified
collagenase I and II. Ans. 14. Thus, Appellants' argument is not persuasive.
The Examiner determined that Pinnell also lacked a disclosure of the
dosages recited by independent claims 1 and 8-that is, "at least about 1500
SRC units" and "at least about 10000 ABC units," respectively. For this the
Examiner determined that Wegman's and Badalemente's disclosures of
these dosages would have been obvious to combine with Pinnell. Final
Action 6, 9; Ans. 17.
Similar to Dwulet, Appellants argue that combining Wegman or
Badalemente is improper because they address different diseases from the
cellulite addressed by Pinnell. Wegman addresses treating Dupytren's
disease with collagenase (Wegman Abstract) and Badalemente addresses
treating adhesive capsulitis with collagenase (Badalemente Abstract) and,
therefore, for the same reasons as set forth above regarding Dwulet, the
Appellants' arguments are not persuasive.
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The Appellants' arguments are largely directed to the references
individually. However, one cannot show nonobviousness by attacking
references individually where the rejections are based on combinations of
references, as they are here. See In re Keller, 642 F.2d 413, 426 (CCPA
1981); In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
The Examiner has established that each limitation of independent
claims 1 and 8 was disclosed by and obvious over the combination of
Pinnell, Dwulet, and Wegman/Badalemente and that there was motivation to
make the combination. Even if this were not conclusive, the limitations
determined by the Examiner not to be disclosed by Pinnell are merely
optimized values of other limitations, i.e., the most desirable components of
collagenase and the level of purity/activity of the enzyme. "[W]here the
general conditions of a claim are disclosed in the prior art, it is not inventive
to discover the optimum or workable ranges by routine experimentation." In
re Aller, 220 F.2d 454, 456 (CCPA 1955).
Claims 9 and 18 (depending from claims 1 and 8, respectively)
Appellants argue separately that claims 9 and 18 are patentable over
the Pinnell, Dwulet, and W egman/Badalemente combination by their
reciting "a volume of about 1.0 ml" with reference to the injection(s) of
purified collagenase I and II. App. Br. 26. However, the Examiner
determined that Pinnell disclosed (col. 3, 11. 48---60) a progression of multiple
injection treatments where the patient received 0.4 ml via four injections at
each treatment, thus after 3 treatments the recited volume of 1.0 ml would be
achieved and exceeded. Ans. 20. We agree with the Examiner's
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determination. The claims do not limit the recited volume administered to
any specific time-frame and, so, the Pinnell disclosure meets this limitation.
Claims 14 and 21 (depending from claims 1 and 8, respectively)
Appellants argue separately that claims 14 and 21 are patentable over
the Pinnell, Dwulet, and W egman/Badalemente combination by their
reciting "the treatment is repeated after about four to about six weeks." App.
Br. 26. However, the Examiner determined that Pinnell disclosed repeating
collagenase injection treatments a month after an initial treatment (which
equates to about 4 weeks). Ans. 20.
For these reasons, the rejections of claims 1, 4, 8-10, 12-14, and 18-
21under35 U.S.C. §103(a) as being unpatentable over Pinnell, Dwulet, and
Wegman/Badalemente are affirmed.
SUMMARY
The rejection of claims 1, 4, 8-10, 12-14, and 18-21under35 U.S.C.
§ 112, second paragraph, is reversed.
The rejections of claims 1, 4, 8-10, 12-14, and 18-21under35
U.S.C. § 103(a) are 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). See 37 C.F.R.
§ 1.136(a).
AFFIRMED
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