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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 6/20/2024, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 15-31 are pending. Claims 15-31 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16, 20, 21, and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 16, the phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 16 is rejected.
Regarding claim 20, claim 20 depends from claim 19. Claim 20 contains the range “0.2 to 2.5 mg/day”. Claim 19 recites “0.5 to 5 mg/day”. Therefore, claim 20 claims a range outside of the claim from which it depends and is not a proper dependent claim and also is indefinite because it is not clear how claim 20 can contain this range of dosage.
Claim 20 is rejected.
Regarding claim 21, claim 21 depends from claim 20. Claim 21 contains the range “0.1 to 2 mg/day”. Claim 20 recites “0.2 to 2.5 mg/day”. Therefore, claim 21 claims a range outside of the claim from which it depends and is not a proper dependent claim and also is indefinite because it is not clear how claim 21 can contain this range of dosage.
Claim 21 is rejected.
Regarding claim 30, the phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 30 is rejected.
Claim Rejections - 35 USC § 102/103
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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 nonobviousness.
Claims 15, 17-25, 27-29, and 31 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Vitali et al. US 8,937,152, published 12/23/2010.
Regarding claim 15, Vitali discloses a cyclic peptide that matches Applicant Formula (I):
“Example 5:
cyclo[Tyr(Bn)-Phe-Pro(4-OCONH(CH2)2NH2)-Phe-(D,L)3,8MNal-Lys]isomer Ba) H-Tyr(Bn)-Phe-Pro(4-OCONH(CH2)2NHBoc)-Phe-(D/L)3,8MNal-Lys(Boc)-OH” (Vitali et al., col. 11, line 31).
The structure is drawn out below:
PNG
media_image1.png
524
612
media_image1.png
Greyscale
Furthermore, Vitali discloses the efficacy of this compound for treating SSTR3 positive tumors:
“The compounds of the invention are also useful in the treatment of tumours positive for the somatostatin receptors, such as for example the tumours which bear the receptors SSTR1, SSTR2, SSTR3 and/or SSTR5, as indicated in the proliferative tests with various cancer cell lines which express the receptors for somatostatin.” (Vitali et al., col. 16, line 38).
Vitali discloses that this compound has the best binding efficacy for SSTR3 for the compounds disclosed by Vitali:
PNG
media_image2.png
171
297
media_image2.png
Greyscale
(Vitali, et al., col. 14, line 45).
All elements of claim 15 are present in Vitali et al.; however, the IC50 table of Vitali shown above provides motivation to select this particular compound of Vitali Example 5 for usage against SSTR3-related tumors.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the compound of Vitali to treat tumors as disclosed by Vitali because Vitali shows that the compound of Example 5 can agonize SSTR3 very effectively and Vitali also discloses that these compounds may treat tumors that express SSTR3.
A person of ordinary skill in the art would be motivated to use this compound because Vitali discloses that the compound of Example 5 can agonize SSTR3 very effectively and Vitali also discloses that these compounds may treat tumors that express SSTR3 and would have a reasonable expectation of success because Vitali discloses that the compound of Example 5 can agonize SSTR3 very effectively and Vitali also discloses that these compounds may treat tumors that express SSTR3.
Consequently, claim 15 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 17, claim 15 is anticipated/obvious as described above. Vitali discloses daily dosing:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al., col. 16, line 49).
Consequently, claim 17 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 18, claim 15 is anticipated/obvious as described above. Vitali discloses the agonism of human receptors:
“The binding assays were carried out, as is explained below, by using preparations of recombinant human receptors, hSSTR1, hSSTR2, hSSTR3 and hSSTR5, obtained from cell membranes (for example CHO) transfected according to standard methods.” (Vitali et al., col. 14, line 18).
Consequently, claim 18 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 19, claim 15 is anticipated/obvious as described above. Vitali discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al., col. 16, line 49).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.5 mg to 5 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 19 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 20, claim 19 is anticipated/obvious as described above. Vitali discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al., col. 16, line 49).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.2 mg to 2.5 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 20 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 21, claim 20 is anticipated/obvious as described above. Vitali discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al., col. 16, line 49).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.1 mg to 2 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 21 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 22, claim 15 is anticipated/obvious as described above. Vitali discloses:
“The present invention also provides pharmaceutical compounds comprising the compounds of formula (I) in free base form or in pharmaceutically acceptable salt form, together with one or more pharmaceutically acceptable excipients or diluents.” (Vitali et al., col. 8, line 30).
Consequently, claim 22 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 23, claim 22 is anticipated/obvious as described above. Vitali discloses:
“The conjugates of the compounds of the invention in complexed form for use in the diagnostic imaging can be administered intravenously, for example in injectable solution or suspension form, preferably in single injection form. The radiotracers can preferably be made just before the patient administration.” (Vitali et al., col. 17, line 8).
Consequently, claim 23 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 24, claim 23 is anticipated/obvious as described above. Vitali discloses:
“The conjugates of the compounds of the invention in complexed form for use in the diagnostic imaging can be administered intravenously, for example in injectable solution or suspension form, preferably in single injection form. The radiotracers can preferably be made just before the patient administration.” (Vitali et al., col. 17, line 8).
Consequently, claim 24 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 25, claim 22 is anticipated/obvious as described above. Vitali discloses:
“The compounds of the invention or their pharmaceutically acceptable salts or complexes can be administered by means of any conventional pathway, for example parenterally, in the form of an injectable solution or suspension (also including the above-indicated modified release forms), orally, using a conventional absorption promoter, nasally or as suppositories or topically, for example in the form of an ophthalmic liquid, gel, preparation as unguent or as suspension, for example liposome suspension, as microsphere or nanosphere formulation, for example for subconjunctival or intra or periocular instillation or injection.” (Vitali et al., col. 8, line 44).
Consequently, claim 25 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 27, claim 22 is anticipated/obvious as described above. Vitali discloses the usage of a suspension:
“The compounds of the invention or their pharmaceutically acceptable salts or complexes can be administered by means of any conventional pathway, for example parenterally, in the form of an injectable solution or suspension (also including the above-indicated modified release forms), orally, using a conventional absorption promoter, nasally or as suppositories or topically, for example in the form of an ophthalmic liquid, gel, preparation as unguent or as suspension, for example liposome suspension, as microsphere or nanosphere formulation, for example for subconjunctival or intra or periocular instillation or injection.” (Vitali et al., col. 8, line 44).
Consequently, claim 27 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 28, claim 15 is anticipated/obvious as described above. Vitali discloses the usage of additional agents:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al., col. 18, line 26).
Consequently, claim 28 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 29, claim 28 is anticipated/obvious as described above. Vitali discloses the usage of additional agents:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al., col. 18, line 26).
Consequently, claim 29 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
Regarding claim 31, claim 28 is anticipated/obvious as described above. Vitali discloses the usage of additional agents that can be administered together or at different times:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al., col. 18, line 26).
Consequently, claim 31 is anticipated by Vitali et al., or in the alternative, obvious over Vitali et al. and rejected.
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 nonobviousness.
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.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Vitali et al. US 8,937,152, published 12/23/2010 in view of Vázquez-Borrego et al. (Vázquez-Borrego, et al. Clinical Cancer Research 26.4: 957-969 (2020)).
Regarding claim 16, claim 15 is anticipated/obvious as described above. Vitali does not explicitly disclose the tumors recited by claim 16.
However, Vázquez-Borrego discloses that SSTR3 agonists can be used to treat non-functioning pituitary adenomas:
“This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.” (Vázquez-Borrego et al., Abstract).
“Most NFPTs are silent gonadotropinomas characterized by lack of hormone hypersecretion, which usually determines a delay in diagnosis and, therefore, are mostly detected as macroadenomas with consequently associated severe comorbidities related to mass effect (i.e., headaches/visual defects/hypopituitarism)” (Vázquez-Borrego et al., page 958, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the SSTR3 agonist of Vitali to treat NFPT as disclosed by Vázquez-Borrego to arrive at the claimed invention because Vitali shows that the compounds disclosed by Vitali are effective agonists of SSTR3, especially the compound claimed by Applicant claim 15.
A person of ordinary skill in the art would use the compound of Vitali to treat NFPT as disclosed by Vázquez-Borrego because Vázquez-Borrego discloses that SSTR3 agonism is an effective treatment as described above.
A person of ordinary skill in the art would have a reasonable expectation of success because Vitali shows that the compound that matches ITF2984 is capable of agonizing SSTR3 and Vázquez-Borrego discloses that this activity has an anti-tumor effect against NFPT.
Consequently, claim 16 is obvious over Vitali et al. in view of Vázquez-Borrego et al. and rejected.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Vitali et al. US 8,937,152, published 12/23/2010 in view of Drucker et al. (Drucker, Daniel J. "Advances in oral peptide therapeutics." Nature reviews Drug discovery 19.4: 277-289 (2020)).
Regarding claim 26, claim 25 is anticipated/obvious as described above.
Vitali does not explicitly disclose the solid forms recited in claim 26.
However, Druker discloses the usage of tablets for the delivery of peptides:
“Tablets containing peptides for oral delivery can be coated with an acid-stable enteric coat to prevent their dissolution in the stomach. Once a tablet leaves the stomach and reaches the upper intestine, the elevation in pH results in dissolution of the enteric coat and release of the tablet contents, as is illustrated for an oral formulation of calcitonin that has been tested in clinical trials43 (see below). Intestinal and pancreatic enzymes are also capable of rapidly degrading peptides. The optimal pH for these gastrointestinal enzymes is neutral to basic; the inclusion of citric acid in the tablet results in a local, transient decrease in pH, resulting in inhibition of the resident peptidases. Indeed, co-administration of citric acid together with oral salmon calcitonin is presumed to enhance bioavailability in part by reducing the activity of local tryptic enzymes, resulting in enhanced absorption of oral salmon calcitonin in beagles.” (Druker et al., page 280, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use tablets as disclosed by Druker to deliver the compound of Vitali to arrive at the claimed invention because Druker discloses that tablets can assist in the pH regulation of peptide drugs.
A person of ordinary skill in the art would make the combination to protect the peptide drug as disclosed by Druker and would have a reasonable expectation of success because Druker states that tablets can regulate pH and protect peptide drugs.
Consequently, claim 26 is obvious over Vitali et al. in view of Druker et al. and rejected.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Vitali et al. US 8,937,152, published 12/23/2010 in view of Morales et al. (Morales, et al. Annual review of medicine 66.1: 17-29. (2015)).
Regarding claim 30, claim 29 is anticipated/obvious as described above. Vitali does not specifically disclose any of the agents recited in claim 30.
However, Morales discloses that metformin is frequently used in cancer treatment regimens:
“Cancer treatment may attempt to cure, reduce tumor growth, relieve symptoms, improve the efficacy of adjuvant therapy, or prevent recurrence. Numerous in vitro and in vivo animal studies have demonstrated growth-inhibiting effects of metformin in breast, endometrial, lung, liver, gastric, and medullary thyroid cancer cell lines (34). Antiproliferative effects have also been demonstrated in several hemopoietic cancer cells, including acute myeloid and promyelocytic leukemia cells. These effects are thought to stem from growth inhibition via cell cycle arrest and from increased cytotoxicity via the induction of apoptosis.” (Morales et al., page 21, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use metformin in conjunction with the cancer treatment of Vitali to arrive at the claimed invention because Morales discloses that metformin is frequently used as part of a cancer treatment regimen.
A person of ordinary skill in the art would be motivated to combine these treatments to increase overall efficacy against cancer or tumors and would have a reasonable expectation of success because Morales discloses that metformin is frequently used in cancer treatment.
Consequently, claim 30 is obvious over Vitali et al. in view of Morales et al. and rejected.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 15, 17-25, 27-29, and 31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of Vitali et al. U.S. Patent No. 8,937,152, published 1/20/2015 in view of Vitali et al. 2 US 20100323964, published 12/23/2010.
Regarding claim 15,
The ‘152 patent discloses the following formula in claim 1:
PNG
media_image3.png
516
596
media_image3.png
Greyscale
Vitali 2 discloses that this cyclic peptide formula can match Applicant Formula (I):
“Example 5:
cyclo[Tyr(Bn)-Phe-Pro(4-OCONH(CH2)2NH2)-Phe-(D,L)3,8MNal-Lys]isomer Ba) H-Tyr(Bn)-Phe-Pro(4-OCONH(CH2)2NHBoc)-Phe-(D/L)3,8MNal-Lys(Boc)-OH” (Vitali et al. 2, para . [0090]).
The structure is drawn out below:
PNG
media_image1.png
524
612
media_image1.png
Greyscale
Furthermore, Vitali 2 discloses the efficacy of this compound for treating SSTR3 positive tumors:
“The compounds of the invention are also useful in the treatment of tumours positive for the somatostatin receptors, such as for example the tumours which bear the receptors SSTR1, SSTR2, SSTR3 and/or SSTR5, as indicated in the proliferative tests with various cancer cell lines which express the receptors for somatostatin.” (Vitali et al. 2, para. [0142]).
Vitali 2 discloses that this compound has the best binding efficacy for SSTR3 for the compounds disclosed by Vitali and Vitali 2:
PNG
media_image2.png
171
297
media_image2.png
Greyscale
(Vitali, et al. 2, para. [0135]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the compound of the ‘152 patent as disclosed by Vitali 2 to treat tumors as disclosed by Vitali 2 because Vitali 2 shows that the compound of Example 5 can agonize SSTR3 very effectively and Vitali also discloses that these compounds may treat tumors that express SSTR3.
A person of ordinary skill in the art would be motivated to use this compound because Vitali 2 discloses that the compound of Example 5 can agonize SSTR3 very effectively and Vitali 2 also discloses that these compounds may treat tumors that express SSTR3 and would have a reasonable expectation of success because Vitali 2 discloses that the compound of Example 5 can agonize SSTR3 very effectively and Vitali 2 also discloses that these compounds may treat tumors that express SSTR3.
Consequently, claim 15 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 17, claim 15 is obvious as described above. Vitali 2 discloses daily dosing:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al. 2, para. [0143]).
Consequently, claim 17 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 18, claim 15 is obvious as described above. Vitali 2 discloses the agonism of human receptors:
“The binding assays were carried out, as is explained below, by using preparations of recombinant human receptors, hSSTR1, hSSTR2, hSSTR3 and hSSTR5, obtained from cell membranes (for example CHO) transfected according to standard methods.” (Vitali et al. 2, para. [0133]).
Consequently, claim 18 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 19, claim 15 is obvious as described above. Vitali 2 discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al. 2, para. [0143]).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.5 mg to 5 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 19 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 20, claim 19 is obvious as described above. Vitali 2 discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al. 2, para. [0143]).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.2 mg to 2.5 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 20 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 21, claim 20 is obvious as described above. Vitali 2 discloses daily dosing in the following amounts:
“ A recommended daily dosage for patients is on the order of about 2 μg up to 50 mg, preferably from about 0.01 to about 40 mg, for example from about 0.001 to about 3 mg s.c. of the compound conveniently administered in divided doses, up to 3 times per day, in single dosage forms containing, for example, from about 0.5 μg to about 25 mg, for example from about 2 μg to about 20 mg, for example from about 2 μg to about 1.5 mg of the invention compounds.” (Vitali et al. 2, para. [0143]).
The range of 0.0001 mg to 3 mg substantially overlaps with 0.1 mg to 2 mg for a daily dose.
MPEP 2131.03(II) states: “When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute."
Alternatively, MPEP 2144.05(I) states: “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).”
Consequently, claim 21 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 22, claim 15 is obvious as described above. The ‘152 patent discloses in claim 20:
“A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, in association with at least one pharmaceutically acceptable excipient.”
Consequently, claim 22 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 23, claim 22 is obvious as described above. Vitali 2 discloses:
“The conjugates of the compounds of the invention in complexed form for use in the diagnostic imaging can be administered intravenously, for example in injectable solution or suspension form, preferably in single injection form. The radiotracers can preferably be made just before the patient administration.” (Vitali et al. 2, para. [0144]).
Consequently, claim 23 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 24, claim 23 is anticipated/obvious as described above. Vitali 2 discloses:
“The conjugates of the compounds of the invention in complexed form for use in the diagnostic imaging can be administered intravenously, for example in injectable solution or suspension form, preferably in single injection form. The radiotracers can preferably be made just before the patient administration.” (Vitali et al. 2, para. [0144]).
Consequently, claim 24 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 25, claim 22 is obvious as described above. Vitali 2 discloses:
“The compounds of the invention or their pharmaceutically acceptable salts or complexes can be administered by means of any conventional pathway, for example parenterally, in the form of an injectable solution or suspension (also including the above-indicated modified release forms), orally, using a conventional absorption promoter, nasally or as suppositories or topically, for example in the form of an ophthalmic liquid, gel, preparation as unguent or as suspension, for example liposome suspension, as microsphere or nanosphere formulation, for example for subconjunctival or intra or periocular instillation or injection.” (Vitali et al. 2, para. [0051]).
Consequently, claim 25 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 27, claim 22 is obvious as described above. Vitali 2 discloses the usage of a suspension:
“The compounds of the invention or their pharmaceutically acceptable salts or complexes can be administered by means of any conventional pathway, for example parenterally, in the form of an injectable solution or suspension (also including the above-indicated modified release forms), orally, using a conventional absorption promoter, nasally or as suppositories or topically, for example in the form of an ophthalmic liquid, gel, preparation as unguent or as suspension, for example liposome suspension, as microsphere or nanosphere formulation, for example for subconjunctival or intra or periocular instillation or injection.” (Vitali et al. 2, para. [0051]).
Consequently, claim 27 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 28, claim 15 is obvious as described above. Vitali 2 discloses the usage of additional agents:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al. 2, para. [0152]).
Consequently, claim 28 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 29, claim 28 is anticipated/obvious as described above. Vitali 2 discloses the usage of additional agents:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al. 2, para. [0152]).
Consequently, claim 29 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Regarding claim 31, claim 28 is anticipated/obvious as described above. Vitali 2 discloses the usage of additional agents that can be administered together or at different times:
“When the compounds of the invention or their conjugates in complexed form are administered in combination with another drug, the doses of the co-administered drugs will of course vary as a function of the conditions to treat and so on. The terms “co-administration” or “combined administration” or the like are used here to signify an administration of the therapeutic agents chosen for a single patient, and intend to include treatment regimes in which the agents are not necessarily administered by the same administration pathway or at the same time.
The particular combination of the invention will be selected depending on whether the disease or disorder must be prevented or treated; for example, a combination with immunosuppressive agent, for example for the prevention or treatment of chronic transplant rejection, a combination with an insulin secretagogue, with a promoter of the insulin secretion, with an insulin sensitiser or with a low insulin dose in the treatment of diabetes and in its complications, a combination with an anti-inflammatory agent for the prevention and treatment of inflammatory diseases or disorders, a combination with an agent with anti-angiogenic effect for the prevention or treatment for example of macular edema or degeneration or cancer, a combination with a chemotherapeutic agent for use in cancer.” (Vitali et al. 2, para. [0152]).
Consequently, claim 31 is obvious over the ‘152 patent in view of Vitali et al. 2 and rejected.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of Vitali et al. U.S. Patent No. 8,937,152, published 1/20/2015 in view of Vitali et al. 2 US 20100323964, published 12/23/2010 as applied to claim 15, further in view of Vázquez-Borrego et al. (Vázquez-Borrego, et al. Clinical Cancer Research 26.4: 957-969 (2020)).
Regarding claim 16, claim 15 is obvious as described above. The ‘152 patent and Vitali 2 do not explicitly disclose the tumors recited by claim 16.
However, Vázquez-Borrego discloses that SSTR3 agonists can be used to treat non-functioning pituitary adenomas:
“This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.” (Vázquez-Borrego et al., Abstract).
“Most NFPTs are silent gonadotropinomas characterized by lack of hormone hypersecretion, which usually determines a delay in diagnosis and, therefore, are mostly detected as macroadenomas with consequently associated severe comorbidities related to mass effect (i.e., headaches/visual defects/hypopituitarism)” (Vázquez-Borrego et al., page 958, col. 1, para. 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the SSTR3 agonist of the ‘152 patent and Vitali 2 to treat NFPT as disclosed by Vázquez-Borrego to arrive at the claimed invention because Vitali shows that the compounds disclosed by Vitali are effective agonists of SSTR3, especially the compound claimed by Applicant claim 15.
A person of ordinary skill in the art would use the compound of the ‘152 patent and Vitali 2 to treat NFPT as disclosed by Vázquez-Borrego because Vázquez-Borrego discloses that SSTR3 agonism is an effective treatment as described above.
A person of ordinary skill in the art would have a reasonable expectation of success because Vitali 2 shows that the compound that matches ITF2984 is capable of agonizing SSTR3 and Vázquez-Borrego discloses that this activity has an anti-tumor effect against NFPT.
Consequently, claim 16 is obvious over the ‘152 patent in view of Vitali et al. 2, further in view of Vázquez-Borrego et al. and rejected.
Claim 26 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of Vitali et al. U.S. Patent No. 8,937,152, published 1/20/2015 in view of Vitali et al. 2 US 20100323964, published 12/23/2010 as applied to claim 25, further in view of Drucker et al. (Drucker, Daniel J. "Advances in oral peptide therapeutics." Nature reviews Drug discovery 19.4: 277-289 (2020)).
Regarding claim 26, claim 25 is obvious as described above.
The ‘152 patent and Vitali 2 do not explicitly disclose the solid forms recited in claim 26.
However, Druker discloses the usage of tablets for the delivery of peptides:
“Tablets containing peptides for oral delivery can be coated with an acid-stable enteric coat to prevent their dissolution in the stomach. Once a tablet leaves the stomach and reaches the upper intestine, the elevation in pH results in dissolution of the enteric coat and release of the tablet contents, as is illustrated for an oral formulation of calcitonin that has been tested in clinical trials43 (see below). Intestinal and pancreatic enzymes are also capable of rapidly degrading peptides. The optimal pH for these gastrointestinal enzymes is neutral to basic; the inclusion of citric acid in the tablet results in a local, transient decrease in pH, resulting in inhibition of the resident peptidases. Indeed, co-administration of citric acid together with oral salmon calcitonin is presumed to enhance bioavailability in part by reducing the activity of local tryptic enzymes, resulting in enhanced absorption of oral salmon calcitonin in beagles.” (Druker et al., page 280, col. 1, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use tablets as disclosed by Druker to deliver the compound of the ‘152 patent and Vitali 2 to arrive at the claimed invention because Druker discloses that tablets can assist in the pH regulation of peptide drugs.
A person of ordinary skill in the art would make the combination to protect the peptide drug as disclosed by Druker and would have a reasonable expectation of success because Druker states that tablets can regulate pH and protect peptide drugs.
Consequently, claim 26 is obvious over the ‘152 patent in view of Vitali et al. 2, further in view of Druker et al. and rejected.
Claim 30 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of Vitali et al. U.S. Patent No. 8,937,152, published 1/20/2015 in view of Vitali et al. 2 US 20100323964, published 12/23/2010 as applied to claim 29, further in view of Morales et al. (Morales, et al. Annual review of medicine 66.1: 17-29. (2015)).
Regarding claim 30, claim 29 is obvious as described above. The ‘152 patent and Vitali 2 do not specifically disclose any of the agents recited in claim 30.
However, Morales discloses that metformin is frequently used in cancer treatment regimens:
“Cancer treatment may attempt to cure, reduce tumor growth, relieve symptoms, improve the efficacy of adjuvant therapy, or prevent recurrence. Numerous in vitro and in vivo animal studies have demonstrated growth-inhibiting effects of metformin in breast, endometrial, lung, liver, gastric, and medullary thyroid cancer cell lines (34). Antiproliferative effects have also been demonstrated in several hemopoietic cancer cells, including acute myeloid and promyelocytic leukemia cells. These effects are thought to stem from growth inhibition via cell cycle arrest and from increased cytotoxicity via the induction of apoptosis.” (Morales et al., page 21, para. 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use metformin in conjunction with the cancer treatment of the ‘152 patent and Vitali 2 to arrive at the claimed invention because Morales discloses that metformin is frequently used as part of a cancer treatment regimen.
A person of ordinary skill in the art would be motivated to combine these treatments to increase overall efficacy against cancer or tumors and would have a reasonable expectation of success because Morales discloses that metformin is frequently used in cancer treatment.
Consequently, claim 30 is obvious over the ‘152 patent in view of Vitali et al. 2, further in view of Morales et al. and rejected.
Conclusion
No claim is allowed.
Claims 15-31 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights