DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on February 21, 2025, wherein claims 1-7, 9-10, 12 and 15-17 are canceled; claims 8 is amended; claims 11, and 13-14 are unchanged; and claim 18 is newly added. Specifically, Applicant deletes the limitations of “with a single injection” and “in a single injection” previously recited in claim 8, and that changes the scope of the claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 8, 11, 13-14 and 18 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 21, 2025 was filed after the mailing date of the Non-Final Office Action on November 20, 2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Action Summary
Applicant’s amendment to the claims overcome each and every objection previously sets
forth in the Non-Final Office Action mailed on November 20, 2024.
Claims 8, 11, and 13-14 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement are withdrawn in light of the claim amendments.
Claims 8, 11 and 13-14 rejected under 35 U.S.C. 103 as being unpatentable over Margulies et al. (US 2022/0016312 A1; cited in IDS filed on October 17, 2023), in view of Kollenda et al. (Acta biomaterialia, 2020. Vol. 109:244–253), and Bihari (US 6,384,044 B1; cited in non-final office action mailed on December 19, 2023) are withdrawn in light of the claim amendments; However, a new ground of rejection is made in view of Margulies et al. (US 2022/0016312 A1), Park et al. (Methods Mol Biol., 2019. Vol. 1914: 295-308) and Bihari (US 6,384,044 B1) as necessitated by claim amendments for the reasons set forth below.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
With regard to claim 8, the term “about” is construed in light of the specification. The specification on page 2, line 25 to page 3, line 1 discloses “All numerical designations, e.g., pH, temperature, time, concentration, amounts, and molecular weight, including ranges, are approximations which are varied(+) or(-) by 10%, 1%, or 0.1%, as appropriate. It is to be understood, although not always explicitly stated, that all numerical designations may be preceded by the term ‘about’”. Therefore, the precise boundaries of the phrase “from about 3.2 mg/mL to about 5.2 mg/mL of naloxone or a salt thereof” is determine by reducing 3.2 mg/mL by 10 % (lower limit) and increasing 5.2 mg/mL by 10% (upper limit) calculated as follows:
l
o
w
e
r
l
i
m
i
t
3.2
m
g
m
L
×
10
100
=
0.32
m
g
m
L
3.2
m
g
m
L
-
0.32
m
g
m
L
=
2.88
m
g
/
m
L
u
p
p
e
r
l
i
m
i
t
5.2
m
g
m
L
×
10
100
=
0.52
m
g
m
L
5.2
m
g
m
L
+
0.52
m
g
m
L
=
5.72
m
g
/
m
L
, and that gives a range of 2.88 mg/mL to 5.72 mg/mL. Furthermore, the phrase “about two-fold” is determine to be 1.9 fold to 2.1 fold by incorporating ± 10%.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8, 11, 13-14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Margulies et al. (US 2022/0016312 A1; cited in IDS filed on October 17, 2023) in view of Park et al. (Methods Mol Biol., 2019. Vol. 1914: 295-308) and Bihari (US 6,384,044 B1; cited in non-final office action mailed on December 19, 2023) (partially newly applied as necessitated by claim amendments).
Margulies teaches a method of repairing a bone defect in a patient in need thereof, comprising applying a bone graft composition, wherein the bone defect is caused by cancer (see e.g., claims 8-9 and 11; [0170]). Margulies et al. further teaches the bone graft composite material is produced by mixing
an appropriate diluent containing an active agent with a powder-dry slurry that is then administered directly and locally to a site of bone injury or surgical intervention where bone graft materials are normally placed to stimulate bone formation (see e.g., [0151]). Margulies et al. further teaches the dry slurry component of the bone graft material containing the following as a percentage of weight: 5% to 12% of iron (III) sulfate, 8% to 11% calcium phosphate dibasic, 9% to 12.5% calcium phosphate tribasic, 13% to 17% hydroxyapatite, 3% to 6% beta-tricalcium phosphate, 4% to 7.5% sodium phosphate dibasic, 11% to 15% sodium carbonate, 2% to 6% calcium oxide, 4% to 6% magnesium oxide, 0.5% to 2.5% L-ascorbic acid, and 18% to 23% powdered type-I collagen (see e.g., [0166]). Margulies further teaches the diluent component of the bone graft material is a solution between 0.5 mL and 12.5 mL in volume composed of the following: 0.9% saline solution, 2% to 6% of acetic acid, 0.1% to 2% citric acid monohydrate, and 0.01% to 2% of naloxone hydrocholoride (see e.g., [0166]). Please note the bone graft composite material taught by Margulies is a composition comprising a salt form of naloxone, iron (II) sulfate, calcium phosphate, and collagen. Margulies further teaches the bone graft compositions containing an active agent with therapeutic properties for treating disease and conditions in which it is desirable or necessary to promote bone growth either by stimulating bone formation or preventing bone destruction (see e.g., [0029]). Margulies further teaches the active agent is an opioid growth factor receptor (OGFR) antagonist, and the OGFR antagonist is selected from the group consisting of naloxone, naltrexone, and a salt thereof (see e.g., [0013]). Margulies further teaches the composition can facilitates repair or regeneration of bone in a human subject (see e.g., [0054]; [0061]), and the bone graft composition comprises an active agent for treating the human disease or condition (see e.g., [0023] and working example 4-5), wherein the human disease or condition is a cancer, and the specific type of cancer include, inter alia, prostate cancer (see e.g., [0025]). Margulies further teaches the compositions and the materials are for bone grafting and repairing and/or filing a void or gap in a bone (see e.g., [0029]). Margulies further teaches the bone graft compositions has improved material properties and improved bioavailability of agents contained in the materials (see e.g., [0029]). Margulies et al. further teaches the bone graft composition can be implanted, extruded, molded, or otherwise placed at the target repair site (see e.g., [0061]; [0175]). Margulies et al. further teaches the target repair site can be, for example, a void, gap, or other defect in a bone or other bony structure in a body of a patient (see e.g., [0061]).
Margulies does not teach the subject in need of decreasing volume of prostate cancer tumor.
Park et al. teaches approximately 80% of advanced prostate cancer metastasizes to bone, yet the mechanisms of its selectiveness and growth in bone remain unclear (see e.g., p. 1, “Introduction” section, 1st paragraph). Park et al. further teaches a large number of animal models have been developed to aid in the study of the molecular pathways of advanced prostate cancer metastasis, including intraosseous injections that allow the implantation of tumor cells directly into a
specific site of interest, such as the femur or tibia (see e.g., p. 2, 1st to 2nd paragraph; p. 6, “3.4 Intraosseous Injection (Intratibial or Intrafemoral)”). Park et al. further teaches that since these tumors grow locally by design, the intraosseous injection is a very reliable and reproducible model to study the interaction between tumor cells and the bone marrow microenvironment, resulting in subsequent tumor growth (see e.g., p. 2, 2nd paragraph).
Bihari teaches a method of treating cancer of the prostate in a human male patient comprising administering an opiate receptor A antagonist, including naloxone (see e.g., claims 1-2; abstract). Bihari et al. further teaches naloxone, has not generally proven to be effective when administered orally; it is available in a form suitable for injection and is better administered by injection (see e.g., Col. 6, line 56-58). Bihari further teaches the action of the compounds of the invention can be employed to terminate
the rapid growth patterns of cancer and related abnormalities, and preventing tumor growth to continue, i.e., reducing the tumor burden (see e.g., Col. 2, line 34-48). Bihari further teaches this aspect of the invention is particularly significant in light of early diagnostic techniques which do reduce tumor size, or with procedures for tumor excision (see e.g., Col. 2, line 48-50).
Please note the bone graft composite material of Margulies et al. is produced by mixing the dry slurry component with the diluent comprising 0.01% to 2% of naloxone hydrocholoride in a solution between 0.5 mL and 12.5 mL in volume (see e.g., [0166]). The actual amount of naloxone hydrocholoride can be calculated as follows:
0.01
%
→
0.01
g
100
m
L
×
1000
m
g
1
g
=
x
m
g
1
m
L
,
x
=
0.1
m
g
/
m
L
2
%
→
2
g
100
m
L
×
1000
m
g
1
g
=
x
m
g
1
m
L
,
x
=
20
m
g
/
m
L
, and that gives a range of 0.1 mg/mL to 20 mg/mL of naloxone hydrochloride. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In the present case, the bone graft composite material of Margulies et al. clearly comprises 0.1 mg/mL to 20 mg/mL of naloxone hydrochloride, and that meets the structural limitation of “about 3.2 mg/mL to about 5.2 mg/mL of naloxone or salt thereof” of the claimed composition.
In the present case, even though Margulies does not specifically exemplify prostate cancer as the cancer causing bone defect in the method of repairing a bone defect, said prior art clearly teaches a list of specific type of cancer that can caused the bone defect, including prostate cancer (see e.g., [0025]), and also teaches the bone defect is caused by a human disease or condition and wherein the bone graft composition comprises an active agent for treating the human disease or condition, e.g., prostate cancer (see claim 9). It would have been prima facie obvious to one of ordinary skilled in the art at the time of application was filed to selectively choose to locally administer the bone graft composite material of Margulies et al. that include naloxone hydrocholoride by implanting said material at the bone defect caused by prostate cancer, where the prostate cancer is localized or metastasized, for reducing volume of the prostate cancer tumor as the bone contains the prostate cancer, rendering the local implantation to the bone that contains the prostate cancer to be contacted by the bone graft composition. Please note the subject in need of repairing bone defect caused by prostate cancer is a subject in need of decreasing volume of a prostate cancer tumor according to page 22 of the instant specification that discloses the cancer includes a cancer that derives from a prostate cancer, e.g., metastases. One would have been motivated to do so, because Park et al. clearly teaches prostate cancer can metastasizes to bone, and Bihari teaches naloxone is useful for treating prostate cancer and reducing tumor size. One of ordinary skill in the art would have a reasonable expectation of success, because one would have reasonably expected that the bone graft composite material of Margulies et al. improves the bioavailability of naloxone hydrocholoride, and therefore locally administering said material to the bone defect caused by prostate cancer can successfully repair said bone defect and treat cancer of the prostate by reducing tumor size. Please note the site of bone defect caused by prostate cancer tumor is a site where the prostate cancer tumor spreads to, and therefore, by locally administering the bone graft composite material of Margulies to said site would necessarily introduce said material into the prostate cancer tumor.
Therefore, it would have been prima facie obvious to one of ordinary skilled in the art at the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant's arguments filed on May 3, 2024 with respect the rejection of claims 8, 11 and 13-14 under 35 U.S.C. 103 as being unpatentable over Margulies et al. (US 2022/0016312 A1) in view of Kollenda et al. (Acta biomaterialia, 2020. Vol. 109: 244-253) and Bihari (US 6,384,044 B1) have been fully considered but they are not persuasive.
Applicant amends independent claim 8 by deleting the limitations of “with a single injection” and “in a single injection”, and that changes the scope of the claims. Therefore, the claim amendment necessitates a modification of rejection on the record. In addition, Applicant adds a new claim 18 that recites “wherein said locally administering comprises implanting the therapeutically effective amount of the composition into the prostate cancer tumor”, and that necessitates a new search and modification of the rejection on the record, including prior arts. As such, the cited prior arts have been revisited and modified in light of the claim amendments.
In Summary, Applicant argues one of ordinary skill in the art would not have any expectation of success for the specific prostate cancer tumor volume reducing effect, which is the limitation of “the volume of the prostate cancer tumor by about two-fold after 14 days compared to a phosphate-based bone cement infused with 0.9% normal saline” in line 6-7 of instant claim 8. Applicant further argues Bihari does not teach or suggest that naloxone is capable of reducing the volume of the prostate cancer tumor because Bihari only teaches oral naltrexone in its examples and does not provide any data for naloxone. Applicant further argues the teachings of Bihari in column 2, line 48-50 is part of Zagon (U.S. Patent No. 4,689, 332), and that reference does not mention prostate cancer at all (see e.g., p. 7, 4th paragraph of the reply filed on May 3, 2024). Applicant further argues the claimed invention demonstrates unexpected results by directing attention to Figure 4 of the specification that shows composition ZP001 decreases the volume of the prostate cancer tumor by about two-fold after 14 days compared to the control that is a phosphate-based bone cement infused with 0.9% of normal saline (see e.g., p. 9, (c) of the reply filed on May 3, 2024).
In response, Applicant’s argument is not found persuasive for the reasons set forth herein. Applicant’s arguments with respect to Kollenda et al. have been considered but are moot because said reference is applied in the prior rejection of record to meet limitation of “with a single injection” recites in the phrase of “locally administering by introduction into the prostate cancer tumor of a subject in need thereof with a single injection… decreases volume of a prostate cancer tumor by about two fold after 14 days compared to a phosphate-based bone cement infused with 0.9% normal saline”. Given that the limitation of “a single injection” is now deleted in light of the claim amendments filed on February 21, 2025, Kollenda et al. can be removed from the basis of the rejection, and that necessitates a modification of the previous rejection on the record.
In response to applicant’s argument with respect to reasonable expectation of success, i.e., “one of ordinary skill in the art would not have any expectation of success for the specific prostate cancer tumor volume reducing effect” (see e.g., p.4, (a)). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In the present case, the bone graft composition of Margulies applied in the method of repairing a bone defect caused by cancer, including prostate cancer, is a composition that meets the structural limitations of the composition as claimed in claims 8, 13 and 14. The difference between the method of Margulies and the claimed method lies on the fact that Margulies does not specifically teach the subject in need of decreasing volume of prostate cancer tumor. However, Margulies clearly provides a working example that demonstrate the placement of the bone graft composition around the implant/polymethylmethacrylatebone cement construct adjacent to bone tissue, including tibia, after subjects undergo a resection of metastatic breast cancer tumor (see e.g., Working Example 5); and further teaches a list of specific cancer that can cause the bone defect, including prostate cancer and breast cancer (see e.g., [0025]). In fact, paragraph [0151] of Margulies teaches the bone graft composite material is produced by mixing an appropriate diluent containing an active agent with a powder-dry slurry that is then administered directly and locally to a site of bone injury or surgical intervention where bone graft materials are normally placed to stimulate bone formation. Park et al. teaches approximately 80% of advanced prostate cancer metastasizes to bone. Just because Bihari does not provide any data for the reduction of tumor volume with naloxone does not mean a person of ordinary skill in the art cannot expect the composition taught by Margulies which is the same composition claimed and the same dose claimed to reduce tumor volume by the amount claimed as naloxone clearly is known to reduce tumor volume.
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005). MPEP 2123.
One would have reasonably recognized that naloxone hydrochloride is the active agent with improved bioavailability in the bone graft composite material of Margulies (see e.g., claims 24 and 26; [0029]), and said agent is also taught by Bihari to be useful for treating cancer of the prostate in a human by reducing tumor size (see e.g., claims 1-2; working examples 1-4). One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by locally administering the bone graft composite material of Margulies to the bone defect caused by prostate cancer can successfully repair said bone defect and treat cancer of the prostate by reducing tumor size. Please note the site of bone defect caused by prostate cancer tumor is a site where the prostate cancer tumor spreads to, and therefore, by locally administering the bone graft composite material of Margulies to said site would necessarily introduce said material into the prostate cancer tumor.
Solely to rebut Applicant’s argument that “Bihari does not teach or suggest that naloxone is capable of reducing the volume of the prostate cancer tumor”, it may well be true that Bihari does not specifically exemplify the administration of naloxone for treating cancer of the prostate in a human male patient in the working examples; However, a prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984). In the present case, Bihari clearly teaches the opiate receptor antagonist useful for treating prostate cancer can includes naloxone or naltrexone in the preferred embodiment (see e.g., claims 1-2), and specifically exemplify the administration of naltrexone has successfully dropped the PSA levels as well as shrinking the tumor masses in patients with prostate cancer (see e.g., Examples 1-4); therefore, the fact that Bihari et al. recites:
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401
443
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(see e.g., Col. 2, line 34-54) that does not specifically mention prostate cancer therein does not constitute a teaching away from using naloxone as an active for treating cancer of the prostate by reducing tumor size.
Furthermore, Applicant’s assertion of unexpected results is not commensurate in scope with the
claimed invention, and said unexpected results would have been expected based on the teachings of prior art references. Specifically, Applicant argues unexpected results are demonstrated in Figure 4 of the specification. It is noted that Figure 4 is the results of the mouse xenograft studies discloses on page 25-26 of the specification. According to page 25 of the instant specification, mice were inoculated with PC3 prostate cancer cells into the bone marrow space of the tibia for 2 weeks, wherein half of the mice were implanted with a control (calcium phosphate based bone cement infused with 0.9% normal saline) and half were implanted with the ZP001. In addition, according to Example 1 on page 24 of the instant specification, ZP001 is a composition with the ingredients as shown below:
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media_image2.png
248
725
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Greyscale
(see e.g., p. 24, Example 1 of the instant specification).
In contrast, claim 8 broadly recites a method of decreasing volume of a prostate cancer tumor comprising locally administering by introduction into the prostate cancer of a subject in need thereof any therapeutically effective amount of a composition comprising from about 3.2 mg/mL to about 5.2 mg/mL of naloxone or a salt thereof, iron (III) sulfate, calcium phosphate, and collagen. It is noted that Applicant only exemplified unexpected result using a single composition species (ZP001) that contains a specific amount of naloxone hydrochloride, iron (III) sulfate, calcium phosphate, and collagen as indicated above, thus, the disclosure does not provide adequate basis for concluding that similar results would be obtained for any other composition species administer at any amounts. In addition, Applicant only exemplify the composition ZP001 is implanted to a single subject species (mice) inoculated with prostate cancer cells PC3 inside the bone marrow space of the tibia, and said disclosure does not provide adequate basis for concluding that similar results would be obtained when said composition is locally introduced into prostate cancer tumor in a different way, including a different location.
According to MPEP 716.02(d), “whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’ In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the present case, the mouse xenograft studies of the specification do not exemplify any other composition species as broadly encompassed by instant claim 8. Furthermore, the disclosure only exemplifies a specific local administration route to introduce the composition ZP001 (“implanted”), and that is not commensurate in scope to encompass any local administration routes. These finding demonstrates that applicant’s assertion of unexpected results is not commensurate in scope with the claimed invention, and therefore, the argument is not found persuasive.
In addition, it is noted that the mouse xenograft studies disclosed in the instant specification utilize an intraosseous injection method to implant tumor cells, in this case, PC3 prostate cancer cells, directly into a tibia as the site of interest known to be useful for studying bone metastatic progression in late-stage advanced prostate cancer patients according to Park et al. (Methods Mol Biol., 2019. Vol. 1914: 295-308) (see e.g., p. 2, 1st to 2nd paragraph; p. 6, “3.4 Intraosseous Injection (Intratibial or Intrafemoral)”). As such, based on the teachings of Margulies et al., Park et al., and Bihari as set forth above, the unexpected results would have been expected, because one would have reasonably expected that locally administering the bone graft composite material of Margulies, which comprises naloxone hydrochloride as the active agent for treating prostate cancer as a human disease or condition, by implanting said material to the site of bone defect caused by prostate cancer would have successfully repair said bone defects by preventing bone destruction caused by prostate cancer, and treat prostate cancer by reducing tumor masses of said cancer.
Solely to rebut Applicant’s augment that Bihari et al. fails to teach a far higher concentration of naloxone for treating prostate tumor by directing attention to Moon (Biochemical and Biophysical Research Communications, 1988. Vol. 153, Issue 2: 722-727) that teaches naloxone at 10-7 M increased prostate cancer cell growth (see page 4-5 of the reply filed on May 3, 2024), it is noted that the amount of naloxone taught by Moon (“10-7 M”) is the concentration used in the in vitro studies to evaluate the growth of prostatic carcinoma cell line DU145 treated with opiate receptor agonists, including dynorphin, rather than the amount administer to a subject in the in vivo studies (see e.g., abstract; p. 723, “materials and methods” section). It may well be true that Moon teaches naloxone appears to have stimulatory effect on prostatic carcinoma cell growth at 10-7 M (see e.g., p. 723, “results” section, 2nd paragraph); However, Moon also teaches opiate antagonist naloxone can block the action of opiate receptor agonist dynorphin-A from stimulating prostate cancer cell growth through the kappa opioid receptor (see e.g., Figure 1; abstract). According to Genders et al. (Neurosci Biobehav Rev., 2020. Vol. 110:133-149), the dynorphins (A and B) are endogenous ligands of the kappa opioid receptors, and both dynorphin and kappa opioid receptors have a widespread distribution within the brain, overlapping with pathways involved in mediating reward and stress (see e.g., p. 137, left column, “2.4 Dynorphin” section, 1st paragraph). These findings demonstrate that the in vitro results of Moon with respect to the stimulatory effect of naloxone may not correlate with what actually happens in vivo, because naloxone can inhibit the stimulatory effect of dynorphin-A that is naturally occurring opioid peptides produced in the body. Please note the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See MPEP § 716.01(c)(II) with regard to Probative Value of Objective Evidence.
Therefore, a new ground of rejection is made, and the previous cited prior arts are revisited and modified as necessitated by claim amendments for the reasons set forth herein.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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