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
Examined Herein: 1-30
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in PR0 62/693,502 on 7/3/2018, PRO 62/693,503 on 7/3/2018, 16/458,261 on 7/1/2019, 17/005,997 on 8/28/2020, 17/584,257 on 1/25/2022, 17/871,825 on 7/22/2022, 18/111,844 on 2/20/2023, and 18/503,027 on 11/6/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/13/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 7/21/2025 are accepted.
Withdrawn Rejections
The rejection of claims 1, 7-16, and 22-30 under 35 U.S.C. 103 over Brock, Hayden, and Stroumpolis are hereby withdrawn in view of Applicant’s amendments to claim 1 and 16. [Remarks 1/28/2026, Page 8]
The rejection of claims 1-3, 7-18 and 22-30 35 U.S.C. 103 over Brock, Hayden, Stroumpoulis, and Sherman are hereby withdrawn in view of Applicant’s amendments to claim 1 and 16. [Remarks 1/28/2026, Page 8]
The rejection of claims 1, 4-16, and 19-30 under 35 U.S.C. 103 over Brock, Hayden, Stroumpoulis, and Aramwit are hereby withdrawn in view of Applicant’s amendments to claim 1 and 16. [Remarks 1/28/2026, Page 8]
The rejection of claims 1-5 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 11,998,604 B2 are hereby withdrawn in view of Applicant’s filing of a terminal disclaimer on 2/26/2026. [Remarks 1/28/2026, Page 15]
The rejection of claims 16-21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,992,530 B2, in view of Hayden are hereby withdrawn in view of Applicant’s filing of a terminal disclaimer on 2/26/2026. [Remarks 1/28/2026, Page 15]
The rejection of claims 1-3 and 5-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,964,018 B2, are hereby withdrawn in view of Applicant’s filing of a terminal disclaimer on 2/26/2026. [Remarks 1/28/2026, Page 16]
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.
Claims 8-10 and 23-25 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 8, 9, 23, and 24 are drawn to administering cisplatin to the patient. In contrast, claims 1 and 16 are drawn to administering a sodium thiosulfate composition to the patient and do not recite a step directed to administering a platinum based chemotherapeutic. While claims 1 and 16 do recite that the patient is “receiving” a platinum based chemotherapeutic treatment, the claims do not recite a step for providing or administering said treatment. Thus, it appears claims 8, 9, 23, and 24 introduce a step of administering cisplatin without providing a clear antecedent basis of this step in claim 1 or 16. Accordingly, it is unclear whether the method of claims 8, 9, 23, and 24 requires an additional step of administering the cisplatin to the patient or whether the method assumes that the patient is already receiving cisplatin once the method commences. If the former, such an additional step must be explicitly recited in the claim language. If the latter, the limitations of claim 8, 9, 23, and 24 are immaterial to the method of claims 1 and 16 because these limitations would be satisfied prior to the commencement of the method. Further clarification is required. Dependent claims fall therewith.
Claim Rejections - 35 USC § 103
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 1-5, 7, 14-20, 22, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman (US 2013/0287676 A1, Published 10/31/2013), in view of Hayden (US 2011/0104257 A1, Published 5/5/2011).
With respect to claim 1 and 16, Sherman discloses a method of reducing ototoxicity comprising:
administering to a human patient who has platinum-induced ototoxicity associated with the use of a platinum based chemotherapeutic, cisplatin, and who is receiving a platinum based chemotherapeutic in combination with an effective amount of a pharmaceutical composition comprising sodium thiosulfate (STS) and borate buffer. [Sherman, 0240, 0252, 0315]
Step (i) is drawn to selecting an adult human patient. This step merely requires performing a mental process which does not constitute a patentable limitation. MPEP 2106.04(a) & 2111.05
Regardless, it is reasonable to conclude that the administration step disclosed by Sherman is necessarily preceded by a patient selection step, as the method requires administering the composition only to a specifically identified patient population.
Also, with respect to claim 1 and 16, Sherman discloses the composition further comprises water. Sherman additionally discloses the amount of STS may be present in an amount of about 1 g to about 12.5 g and the volume of water may be about 1 mL to about 25 mL. [Sherman, 0159]
With respect to claim 2 and 17, Sherman discloses the composition further comprises a pH adjusting agent, sodium hydroxide. [Sherman, 0315] Sherman further discloses the pH adjusting agent may be hydrochloric acid. [Sherman, 0187]
With respect to claim 3 and 18, Sherman discloses the composition further comprises sodium hydroxide. [Sherman, 0315]
With respect to claim 4, 5, 19, and 20, Sherman discloses the composition has a pH between 6 and 8. [Sherman, 0043]
With respect to claim 7 and 22, Sherman discloses the platinum based chemotherapeutic is cisplatin. [0240]
Sherman does not disclose the human patient is an adult who has a germ cell cancer or the sodium thiosulfate is at a concentration of about 0.5 M or the borate buffer is at a concentration of about 0.004 M or the concentration of borate ions is less than 0.05%.
However, with respect to claim 1 and 16, Hayden discloses cisplatin induces ototoxicity in adult patients. [Hayden, 0012] Hayden further discloses cisplatin is used in the treatment of testicular and ovarian cancer. [Hayden, 0007] Testicular and ovarian cancers are germ cell cancers.
With respect to claim 14 and 29, Hayden discloses the germ cell cancer in the adult human patient is testicular cancer. [Hayden, 0007, 0012]
With respect to claim 15 and 30, Hayden discloses the germ cell cancer in the adult human patient is ovarian cancer. [Hayden, 0007, 0012]
Moreover, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. In the instant case, the general conditions of the claims are disclosed by Sherman and Hayden, as described above and below. Thus, it is not inventive to discover the optimum or workable concentration of STS, borate buffer, or borate ions by routine experimentation. MPEP 2144.05 (II)(A)
Modifying the method disclosed by Sherman so that pharmaceutical composition comprises 1.25 g of STS and 10 mL of water results in a composition comprising:
1.25 g of STS pentahydrate,
4.40 mg of potassium chloride,
2.80 mg of boric acid buffer, and
10 mL of water.
In which case, the sodium thiosulfate is at a concentration of about 0.5 M and the borate buffer is at a concentration of about 0.004 M (or less than 0.05 % of borate ions).
Further modifying method disclosed Sherman so that the human patient that has platinum-induced ototoxicity associated with the use of cisplatin is an adult who has germ cell cancer, results in the method of claim 1, 14-16, 29, and 30.
It would have been routine optimization to arrive at the claimed invention by modifying the concentration of sodium thiosulfate, borate buffer, and/or borate ions. Sherman discloses the pharmaceutical composition comprising STS may be formulated into dosage units and such dosage units may be adjusted according to the patient’s condition and treatment needs. [Sherman, 0245, 0246] Sherman further discloses that the amount of sodium thiosulfate and water present in the composition may vary. Specifically, Sherman discloses the pharmaceutical composition may comprise about 1 to about 100 grams of sodium thiosulfate and about 1 to 1000 mL or more of water. [Sherman, 0159] Therefore, Sherman establishes that the concentration of STS is an adjustable variable that may be varied to formulate dosage units appropriate for the patient’s condition and treatment needs. Modifying the amount of STS and volume of water necessarily affects the concentration of other components in the composition, including borate buffer and borate ions. A person of ordinary skill in the art would have had a reasonable expectation of success in formulating the claimed concentration because Sherman discloses, in a specific embodiment, the amount of STS may be about 1 gram to about 12.5 grams and the volume of water may be about 1 mL to 25 mL. Thus, a POSITA would reasonably select an amount of STS and a volume of water within this range to formulate a dosage unit that provides a concentration necessary to achieve a desired therapeutic effect.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman so that the human patient who has platinum-induced ototoxicity associated with the use of cisplatin is an adult patient who further has germ cell cancer (testicular or ovarian cancer) and have a reasonable expectation of success. Sherman discloses a method comprising administering to a human patient who has platinum-induced ototoxicity due to the use of cisplatin a combination therapy comprising cisplatin with a pharmaceutical composition comprising sodium thiosulfate. Hayden discloses that cisplatin induces ototoxicity in adult patients and is used in the treatment of testicular and ovarian cancer, which are germ cell cancers. Thus, Hayden establishes that a human patient with platinum-induced ototoxicity associated with the use of cisplatin may be an adult human patient who is receiving cisplatin. Hayden further establishes that a human patient who is receiving cisplatin may be a patient afflicted with testicular or ovarian cancer and in need of treatment. Accordingly, the combined teachings of Sherman and Hayden suggest that the human patient with platinum-induced ototoxicity due to the use of cisplatin disclosed in the method disclosed by Sherman may be an adult human patient suffering from cisplatin-induced ototoxicity and receiving cisplatin for the treatment of testicular or ovarian cancer. Therefore, it is reasonable to expect the method disclosed by Sherman may be modified so that the human patient who has platinum-induced ototoxicity due to the use of cisplatin is also an adult who has germ cell cancer. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Hayden discloses cisplatin, which is used to treat testicular and ovarian cancer, is one of the most ototoxic drugs in clinical use, causing severe, permanent, bilateral hearing loss in 10-25% of adult patients. [Hayden, 0007, 0012] Accordingly, one would have been motivated by the expected beneficial result of treating ototoxicity in this patient population using the method disclosed by Sherman.
Claims 1-5, 7, 12-20, 22, and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Hayden, as applied to claim 1-5, 7, 14-20, 22, 29, and 30 above, and further in view of Pamucku (US 2001/0012858 A1, Published 8/9/2001).
With respect to claim 1 and 16, Sherman and Hayden disclose the teachings above.
Recall, the combined teachings of Sherman and Hayden suggest that the human patient is an adult human patient suffering from cisplatin-induced ototoxicity and receiving cisplatin for the treatment of testicular or ovarian cancer. Moreover, Sherman and Hayden disclose a first therapy, cisplatin, may be administered prior to administering a second therapy, the STS composition. [Sherman, 0248-0252]
Sherman and Hayden do not disclose the germ cell cancer in the adult human patient is disseminated or metasized.
However, with respect to claim 12, 13, 27, and 28, Pamucku discloses that cisplatin is used to treat metastatic testicular or ovarian tumors in patients. [Pamucku, 0004] Metastasis is a type of tumor cell dissemination.
Modifying the method disclosed by Sherman and Hayden so that the testicular or ovarian cancer in the patient is metastatic testicular or metastatic ovarian cancer results in the method of claim 12, 13, 27, and 28.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman and Hayden so that the testicular or ovarian cancer in the patient is metastasized (or disseminated) and have a reasonable expectation of success. Sherman and Hayden disclose a method comprising administering to an adult human patient suffering from cisplatin-induced ototoxicity and testicular or ovarian cancer, a combination therapy comprising cisplatin with a pharmaceutical composition comprising sodium thiosulfate. Hayden discloses that cisplatin induces ototoxicity in adult patients and is used in the treatment of testicular and ovarian cancer, which are germ cell cancers. Pamukcu discloses cisplatin is used to treat metastatic testicular or ovarian tumors in patients. Thus, Pamukcu establishes that a human patient receiving cisplatin may be a patient suffering from metastatic testicular or ovarian cancer. Accordingly, the combined teachings of Sherman, Hayden, and Pamucku suggest that the adult human patient suffering from cisplatin-induced ototoxicity and receiving cisplatin for the treatment of testicular or ovarian cancer may be a patient suffering from metastatic testicular or metastatic ovarian cancer, specifically. Therefore, it reasonable to expect the method disclosed by Sherman and Hayden may be modified so that the treated patient is an adult human patient suffering from cisplatin-induced ototoxicity and receiving cisplatin for the treatment of metastatic testicular or ovarian cancer. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Pamucku discloses that cisplatin is typically used as a treatment for metastatic testicular and ovarian tumors in patients who have already received appropriate surgical or radiotherapeutic treatment. [Pamucku, 0004] Accordingly, one would have been motivated by the expected beneficial result of treating ototoxicity in this patient population using the method disclosed by Sherman and Hayden.
Claims 1-5, 7-9, 11, 14-20, 22, 24, 26, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Hayden, as applied to claims 1-5, 7, 14-20, 22, 26, 29, and 30 above, and further in view of Campbell (US 6,265,386 B1, Published 7/24/2001).
With respect to claim 1, 7, 16, and 22, Sherman and Hayden disclose the teachings above.
Recall, the combined teachings of Sherman and Hayden suggest that the human patient is an adult human patient suffering from cisplatin induced ototoxicity and receiving cisplatin for the treatment of germ cell cancer (testicular or ovarian cancer).
With respect to claim 9 and 24, Sherman discloses the method may comprise administering a second therapy, the STS composition, to the human patient about 6 hours after the completion of administering a first therapy, cisplatin. [Sherman, 0248-0252]
Sherman and Hayden do not disclose that the germ cell cancer in the adult human patient is localized or the cisplatin is administered to the human patient as an infusion over 1 to 6 hours.
However, with respect to claim 8 and 23, Campbell discloses cisplatin may be administered as an infusion over a 6-hour period. [Col. 15, Line 66-67 and Col. 16, Line 4-6]
With respect to claim 11 and 26, Campbell discloses cisplatin is used to treat localized testicular or ovarian tumors. [Col. 15, Line 66-67 and Col. 16, Line 1-7]
Modifying the method disclosed by Sherman and Hayden so that the cisplatin is administered to the patient as an infusion over 6 hours results in the method of claim 8, 9, 23, and 24.
Modifying the method disclosed by Sherman and Hayden so that the testicular or ovarian cancer in the patient is localized testicular or ovarian cancer results in the method of claim 11 and 25.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman and Hayden so that the cisplatin is administered to the patient as an infusion over 6 hours and have a reasonable expectation of success. Sherman and Hayden disclose a method comprising administering to an adult human patient suffering from cisplatin-induced ototoxicity and testicular or ovarian cancer, a combination therapy comprising cisplatin and a pharmaceutical composition comprising sodium thiosulfate. Campbell discloses cisplatin is typically administered to patients with testicular or ovarian cancer as an infusion over a 6-hour period. Thus, Campbell establishes that a 6-hour cisplatin infusion is a known administration practice for patients with testicular or ovarian cancer. Accordingly, the combined teachings of Sherman, Hayden, and Campbell suggest that the adult human patient suffering from cisplatin induced ototoxicity and receiving cisplatin for the treatment of testicular or ovarian cancer in the method disclosed by Sherman and Hayden may be administered cisplatin as a 6-hour infusion. Therefore, it reasonable to expect the method disclosed by Sherman and Hayden may be modified so that the cisplatin is administered to the patient as an infusion over 6 hours. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Campbell discloses that administering cisplatin via an infusion over 6-hours is a clinically accepted approach. [Col. 15, Line 66-67 and Col. 16, Line 1-7] Therefore, one would have been motivated by the expectation that administering cisplatin as an infusion over 6 hours to the patient in the method disclosed by Sherman and Hayden would align with known clinical administration practices.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman and Hayden so that the testicular or ovarian cancer in the patient is localized and have a reasonable expectation of success. Sherman and Hayden disclose a method comprising administering to an adult human patient suffering from cisplatin-induced ototoxicity and testicular or ovarian cancer, a combination therapy comprising cisplatin and a pharmaceutical composition comprising sodium thiosulfate. Hayden discloses that cisplatin induces ototoxicity in adult patients and is used in the treatment of testicular and ovarian cancer, which are germ cell cancers. Campbell discloses that cisplatin is used to treat localized testicular and ovarian tumors in patients. Thus, Campbell establishes that a human patient receiving cisplatin may be a patient suffering from metastatic testicular or metastatic ovarian cancer. Accordingly, the combined teachings of Sherman, Hayden, and Campbell suggest that the adult human patient suffering from cisplatin-induced ototoxicity and receiving cisplatin for the treatment of testicular or ovarian cancer may be a patient suffering from localized testicular or ovarian cancer, specifically. Therefore, it reasonable to expect the method disclosed by Sherman and Hayden may be modified so that the testicular or ovarian cancer in the patient is localized. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Campbell discloses that cisplatin is used to treat localized lesions in testicular cancer and ovarian tumors. [Campbell, Col. 15, Line 66-67 and Col. 16, Line 1-7] Accordingly, one would have been motivated by the expected beneficial result of treating ototoxicity in this patient population using the method disclosed by Sherman and Hayden.
Claims 1-5, 7, 10, 14-20, 22, 25, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Hayden, as applied to claims 1-5, 7, 14-20, 22, 29, and 30 above, and further in view of Brock (Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss, 6/21/2018, N Engl J Med, 378(25):2376-2385).
With respect to claim 1 and 16, Sherman and Hayden disclose the teachings above.
Sherman and Hayden do not disclose the pharmaceutical composition is administered as an infusion over about 15 minutes.
However, with respect to claim 10 and 25, Brock discloses a method of reducing ototoxicity in a human patient receiving a platinum based chemotherapeutic comprising administering an effective amount of a pharmaceutical composition comprising sodium thiosulfate and borate buffer. [Brock, Abstract][Brock, Protocol, Page 42/151, “12.1.2 Sodium Thiosulphate”] Brock discloses the composition is administered as an infusion over about 15 minutes. [Brock, Abstract][Brock, Protocol, Page 44/151, “12.5 Administration”]
Modifying the method disclosed by Sherman and Hayden by administering the STS composition as an infusion over about 15 minutes results in the method of claim 10 and 25.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman and Hayden by administering the STS composition as an infusion over about 15 minutes and have a reasonable expectation of success. Sherman and Hayden disclose a method of treating ototoxicity in a subject comprising administering a sodium thiosulfate composition to a patient via infusion. Brock discloses a method of treating ototoxicity in a subject comprising administering a sodium thiosulfate composition to a patient via an infusion over about 15 minutes. Thus, Brock establishes that administering an STS composition via an infusion over about 15 minutes is sufficient to provide a therapeutic effect for treating ototoxicity. Accordingly, the combined teachings of Sherman, Hayden, and Brock suggest that the STS composition in the method for treating ototoxicity disclosed by Sherman and Hayden may be administered to a patient via an infusion over about 15 minutes. Therefore, it is reasonable to expect that the method disclosed by Sherman and Hayden may be modified by administering the STS composition as an infusion over about 15 minutes. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Brock discloses that the STS composition may be administered via an infusion over 15 minutes and demonstrates that this administration is associated with reduced ototoxicity. [Brock, Protocol, Page 29/151, Paragraph 2] Therefore, one would have been motivated by the expectation that administering the STS composition to a patient via an infusion according to the method disclosed by Sherman and Hayden over 15 minutes could be sufficient to reduce ototoxicity in said patient.
Claims 1-7, 14-22, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Sherman and Hayden, as applied to claims 1-5, 7, 14-20, 22, 29, and 30 above, and further in view of Aramwit (US 2005/0080046 A1, Published 4/14/2005).
With respect to claim 1 and 16, Sherman and Hayden disclose the teachings above.
Recall, Sherman and Hayden disclose that the STS composition may be administered via an infusion. [Sherman, 0245-0246]
Sherman and Hayden do not disclose the pharmaceutical composition has a pH between 8.6 and 8.8.
However, with respect to claim 4-6 and 19-21, Aramwit discloses that injectable formulations maintained at isotonic pH of about 3.5 to about 8.5 are generally considered to be most comfortable, safe and/or tolerable for a subject receiving the formulation, particularly where such a formulation is to be intravenously infused. [Aramwit, 0034]
Modifying the method disclosed by Sherman and Hayden by adjusting the pH of the STS composition to between 5 and about 8.5 (which includes 8.6) results in the method of claim 4-6 and 19-21.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Sherman and Hayden by adjusting the pH of the STS composition to between 5 and about 8.5 (which includes 8.6) and have a reasonable expectation of success. Sherman and Hayden disclose a method comprising administering a pharmaceutical composition via an injection (IV infusion). Aramwit discloses that compositions administered via injection, specifically IV infusion, should maintain an isotonic pH of 3.5 to about 8.5. Thus, Aramwit establishes that injectable formulations may be formulated to maintain an isotonic pH, which ensures a safe and tolerable administration. Accordingly, the combined teachings of Sherman, Hayden, and Aramwit suggest that the pharmaceutical composition administered via IV infusion in the method disclosed by Sherman and Hayden may be formulated to maintain an isotonic pH of 3.5 to about 8.5. Therefore, it is reasonable to expect the method disclosed by Sherman and Hayden may be modified by adjusting the pH of the pharmaceutical composition to between 5 and about 8.5 (which includes 8.6). One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II) In the instant case, Aramwit discloses injectable formulations maintained at isotonic pH of about 3.5 to about 8.5 are generally considered to be most comfortable, safe and/or tolerable for a subject receiving the formulation. [Aramwit, 0034] Accordingly, one would have been motivated by the expectation that the aforementioned modification would provide a more safe and tolerable administration to the patient in the method disclosed by Sherman and Hayden.
Response to Arguments
Applicant asserts “This formulation with lower borate concentration is more advantageous for administration than the prior formulations. When intravenously administered six hours after completion of cisplatin infusion, PEDMARK significantly decreases the incidence of hearing loss (21.4% in the treatment group vs 73.3% in the standard of care for the COG ACCL043 l trial and 32.7% in the treatment group vs 63% in the standard of care group in the SIOPEL6 trial (see September 21, 2022, Fennec Press Release Announcing FDA Approval of PEDMARK; Attachment C)).” [Remarks 1/28/2026, Page 10, Paragraph 2]
Applicant’s allegations of unexpected results are noted. However, Applicant has not provided any evidence to support the assertion that the claimed invention is more advantageous than prior formulations or exhibits unexpected results compared to prior formulations. Arguments presented by an Applicant cannot take the place of evidence in the record.
Applicant is encouraged to submit evidence demonstrating that the claimed invention achieves greater than expected results in accordance with MPEP 716.02.
Applicant’s assertion with respect Brock have been considered but are moot because the new ground of rejection does not rely on any teaching specifically challenged in the argument. [Remarks 1/28/2026, Page 10, Paragraph 3 & Page 11, Paragraph 5]
Applicant asserts “Hayden does not cure the defects of Brock because Hayden is related to the field of genetic markers for adverse drug reaction (see [0001]) and there is no sodium thiosulfate formulation nor borate mentioned in Hayden.” [Remarks 1/28/2026, Page 12, Paragraph 1]
Applicant’s assertion is not persuasive because it is drawn to a teaching by Hayden that was not relied on and does not form the basis of the instant rejection. The instant rejection does not rely on Hayden to teach a sodium thiosulfate formulation. Rather, Hayden is relied on to establish that cisplatin induces ototoxicity in adult patients receiving treatment for testicular or ovarian cancer. Accordingly, Applicant’s criticism of Hayden fails to undermine the basis of the rejection.
Applicant’s assertion with respect Stroumpoulis have been considered but are moot because the new ground of rejection does not rely on any teaching from Stroumpoulis. [Remarks 1/28/2026, Page 12, Paragraph 2-3 & Page 13, Paragraph 1-2]
Applicant asserts “Sherman does not cure the defects of Brock, Hayden, and Stroumpoulis and instead teaches away from the claimed invention because Sherman teaches that a concentration of at least 0.045 M boric acid is needed to stabilize STS.” [Remarks 1/28/2026, Page 13, Paragraph 3]
Applicant’s assertions are not persuasive because disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. MPEP 2123(II) Moreover, a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed. MPEP 2145(X)(D)(1)
Applicant asserts “This working example establishes a minimum concentration of boric acid which is at least five times higher than the concentration used in the present invention.” [Remarks 1/28/2026, Page 13, Paragraph 4]
Applicant’s arguments are not persuasive because Sherman explicitly states “The examples set forth above are provided to give those of ordinary skill in the art with a complete disclosure and description of how to make and use the claimed embodiments, and are not intended to limit the scope of what is disclosed herein.” [Sherman, 0315] Therefore, Sherman makes it clear that the working examples do not establish a minimum concentration of boric acid or impose any limitations on the scope of disclosure. Rather, the broader disclosure of Sherman encompasses concentrations outside of the exemplified concentration.
Applicant asserts “The only teaching in Sherman related to changing the concentration of boric
acid indicates that a higher concentration should be used. Sherman and the corresponding NITHIODOTE label recite that the concentration of boric acid can be increased to achieve the target pH (see Table 8 of Sherman and page 9 of Attachment B). [Remarks 1/28/2026, Page 13, Paragraph 3 & Page 14, Paragraph 1]
Applicant cites Table 8 of Sherman to support the assertion that Sherman teaches changing the concentration of boric acid to a higher concentration. However, Table 8 provides no such teaching. In fact, Sherman does not appear to discuss modifying the concentration of boric acid at all. Nonetheless, Sherman does disclose modifying the concentration of the other components present in the composition, such as STS, and modifying the volume of the solvent (water) in the composition. Modifying the volume of solvent necessarily changes the concentration of boric acid because concentration is a function of solute and solvent volume.
Moreover, Applicant cites to a NITHIODOTE label (see Attachment B) and alleges the label corresponds with Sherman. However, Sherman does not teach or suggest any association with the cited label. Accordingly, Applicant has not established that the label is representative of or provides a sufficient nexus to the Sherman disclosure.
Applicant asserts “The STS formulation described in Sherman is not appropriate for use in reducing ototoxicity in cancer patients because the concentration of borate is too high.” [Remarks 1/28/2026, Page 14, Paragraph 1]
Applicant’s assertion is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. The instant rejection relies on Sherman and Hayden, not Sherman alone. Sherman discloses a method for treating or preventing platinum-induced ototoxicity associated with the use of cisplatin or other platinum-containing medications by administering a therapeutically effective amount of sodium thiosulfate, and Hayden discloses that cisplatin is administered to cancer patients. Sherman provides no teaching or suggestion that would lead a POSITA to believe that the concentration of borate is unsuitable for this purpose, nor has Applicant provided evidence to support this assertion.
Applicant asserts “Aramwit is not related to a sodium thiosulfate formulation with a very low concentration of borate. Aramwit describes storage stable pharmaceutical formulations comprising eplerenone (see Abstract) and does not mention any sodium thiosulfate formulation nor borate buffer.” [Remarks 1/28/2026, Page 14, Paragraph 3]
Applicant’s assertion is not persuasive because it is drawn to a teaching by Aramwit that was not relied on and does not form the basis of the instant rejection. The instant rejection does not rely on Aramwit to teach a sodium thiosulfate formulation. Rather, Aramwit is relied on to establish that injectable formulations maintained at isotonic pH of about 3.5 to about 8.5 are generally considered to be most comfortable, safe and/or tolerable for a subject receiving the formulation. Accordingly, Applicant’s criticism of Aramwit fails to undermine the basis of the instant rejection.
Applicant asserts “Even if Aramwit described the use of borate buffer to stabilize eplerenone, which it does not, the skilled artisan would not combine the teachings of Aramwit with Brock, because eplerenone is structurally very different than sodium thiosulfate and thus requires different excipients for stabilization.” [Remarks 1/28/2026, Page 14, Paragraph 4 & Page 15, Paragraph 1]
Applicant is encouraged to clarify this assertion because it is not clear what differences in excipients Applicant is referring to or how this alleged difference would render Aramwit’s teachings regarding the appropriate pH for injectable formulations inapplicable to the method disclosed by Sherman and Hayden, which comprises administering an injectable formulation to a subject.
Conclusion
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 KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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, Michael Hartley can be reached at 571-272-0616. 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.
/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618