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
The instant application is a national stage entry of PCT/EP2023/056761, filed March 16, 2022.
Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) by application no. EP22305311.7, filed in the European Patent Office on March 16, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 8, 2025 was in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents was considered. A signed copy of form 1449 is enclosed herewith.
Status of Claims
5. Claims 16-32 are pending and under consideration in the instant application.
Claim Rejections - 35 USC § 112
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 16-32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the therapeutic treatment of SSNHL, does not reasonably provide enablement for prophylactic treatment/prevention of the claimed disorders/conditions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
The above factors, regarding the present invention, are summarized as follows:
(a) Breadth of the claims - The breadth of the claims is drawn to methods for preventing SSNHL
(b) Nature of the invention - The nature of the invention is therefore drawn to the pharmaceutical art.
(c,e) State of the prior art and predictability in the art - The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat or prevent which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic or preventative regimen on its face.
SSNHL is an unexplained, rapid loss of hearing either all at once or over a few days. SSHL happens because there is something wrong with the sensory organs of the inner ear. Sudden deafness frequently affects only one ear. What causes sudden deafness?
A variety of disorders affecting the ear can cause SSHL, but only about 10 percent of people diagnosed with SSHL have an identifiable cause. Some of these conditions include: Infections. Head trauma. Autoimmune diseases. Exposure to certain drugs that treat cancer or severe infections. Blood circulation problems. Neurological disorders, such as multiple sclerosis. Disorders of the inner ear, such as Ménière’s disease. Sudden Sensorineural Hearing Loss (SSHL) | NIDCD There is no current prevention for SSNHL.
The specification defines treatment as follows:
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Regarding the prevention - prophylaxis and/or prevention means to anticipate or counter in advanced, to keep from happening, etc. and there is no disclosure as to how one skilled in the art can reasonably establish the basis and the type of subject to which the instant compounds and compositions can be administered in order to have the "preventive" effect. How would one show a correlation that the diseases of the instant claims are prevented by the compounds of the invention, or that the subject would not have contracted the disease without administration of the instantly claimed compounds/compositions? How is the initial onset of the claimed diseases prevented?
The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any preventative regimen on its face.
(d) Level of one of ordinary skill in the art - The artisans using applicant’s method would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art, it is noted that the claimed compound is required to be assessed for physiological activity by in vitro or in vivo screening to determine if it exhibits the desired pharmacological activity and which diseases would benefit from this activity.
(f-g) Amount of direction provided by the inventor and existence of working examples - The only direction or guidance present in the instant specification is the listing of diseases applicant considers as treatable and preventable by the claimed compounds and composition comprising the same.
There are absolutely no working examples present for the prevention of any conditions.
The inhibitory and biological assay data of the specification supports the treatment of the claimed disorders; however, not preventing the full scope of aforementioned conditions.
Test assays and procedures are provided in the specification and the disclosure does not provide how the in vitro and in vivo data correlates to the prevention of the full scope of diseases, as claimed.
Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Applicant has not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use for preventing the claimed diseases comprising administration of the claimed compounds or pharmaceutical compositions.
(h) Quantity of experimentation needed to make or use the invention based on the content of the disclosure - The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine if the claimed compounds/compositions of the instant invention would provide treatment and prevention of the claimed diseases.
A person having ordinary skill in the art at the time the invention was made would be faced with an undue amount of experimentation to use the pharmaceutical compositions for the full scope of the claimed intended uses.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 102
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.
8. Claim(s) 16-19, 21, and 26-31 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US20180207167.
US20180207167 teaches a method for treating SSNHL comprising administering azasetron and benzoxazine compounds, starting at [0011], [0086]-[0087], disclosing that the subject to be treated may show a decrease in hearing 80 dB, 90 dB or more [0023], [0076]-[0089], [0187], Figures 2 and 3, and further discloses a hearing loss at baseline affecting frequencies equal to or lower than 2000 Hz [0078]. Azasetron analogs of present claim 27 are taught in ‘167 claim 20. Hearing loss of present claim 21, is taught at [0024], the hearing loss being unilateral. Dosages of instant claims 28-30 are taught starting at [0136].
Claim Rejections - 35 USC § 103
9. 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.
10. 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.
11. 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.
12. Claim(s) 16-19 and 21-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over US20180207167 in view of Petremann et al. [Petremann, Mathieu. SENS-401 Effectively Reduces Severe Acoustic Trauma-Induced Hearing Loss in Male Rats With Twice Daily Administration Delayed up to 96hours, Otology & Neurology, 40: 254-263, 2019].
US20180207167 teaches a method for treating SSNHL comprising administering azasetron and benzoxazine compounds, starting at [0011], [0086]-[0087], disclosing that the subject to be treated may show a decrease in hearing 80 dB, 90 dB or more [0023], [0187], Figures 2 and 3, and further discloses a hearing loss at baseline affecting frequencies equal to or lower than 2000 Hz [0078]. Azasetron analogs of present claim 27 are taught in ‘167 claim 20. Hearing loss of present claim 21, is taught at [0024], the hearing loss being unilateral. Dosages of instant claims 28-30 are taught starting at [0136].
Petremann et al. teaches SENS-401, the (R)-azasetron besylate salt of claims 22-25.
Regarding the combination of references, MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at ___, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Based on the teachings of the MPEP and KSR above, by employing the rationale in A, F, and G above, it would have been obvious for one of ordinary skill in the art to make the aforementioned modifications and arrive at the presently claimed invention. One of ordinary skill in the art would be motivated to administer (R)-azasetron besylate of Petremann et al., for the treatment of SSNHL according to parameters of US20180207167, to arrive at the presently claimed invention.
If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See MPEP 2145.
Please note that if Applicant intends to rely on unexpected or unforeseen results, attention is invited to MPEP 716. Absent clear, convincing, side-by-side data demonstrating unobviousness vis-à-vis the prior art commensurate with the scope of protection sought, the claims are considered prima facie obviousness.
13. Claim(s) 16-24 and 26-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over US20180207167 in view of US 20190083503.
US20180207167 teaches a method for treating SSNHL comprising administering azasetron and benzoxazine compounds, starting at [0011], [0086]-[0087], disclosing that the subject to be treated may show a decrease in hearing 80 dB, 90 dB or more [0023], [0187], Figures 2 and 3, and further discloses a hearing loss at baseline affecting frequencies equal to or lower than 2000 Hz [0078]. Azasetron analogs of present claim 27 are taught in ‘167 claim 20. Hearing loss of present claim 21, is taught at [0024], the hearing loss being unilateral. Dosages of instant claims 28-30 are taught starting at [0136].
US 20190083503 teaches a method of treating ear disorders, such as SSNHL [0021] comprising administering azasetron and (R)-azasetron and (S)-azasetron and besylate salts thereof. US 20190083503 teaches idiopathic SSNHL [0085].
Regarding the combination of references, MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at ___, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Based on the teachings of the MPEP and KSR above, by employing the rationale in A, F, and G above, it would have been obvious for one of ordinary skill in the art to make the aforementioned modifications and arrive at the presently claimed invention. One of ordinary skill in the art would be motivated to administer the compounds of US 20190083503 for the treatment of idiopathic SSNHL according to parameters of US20180207167, to arrive at the presently claimed invention.
If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See MPEP 2145.
Please note that if Applicant intends to rely on unexpected or unforeseen results, attention is invited to MPEP 716. Absent clear, convincing, side-by-side data demonstrating unobviousness vis-à-vis the prior art commensurate with the scope of protection sought, the claims are considered prima facie obviousness.
14. Claim(s) 16-19, 21, and 26-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over US20180207167 in view of Wei et al. [Wei BPC, Stathopoulos D, O'Leary S. Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD003998. Pg 1-38]
US20180207167 teaches a method for treating SSNHL comprising administering azasetron and benzoxazine compounds, starting at [0011], [0086]-[0087], disclosing that the subject to be treated may show a decrease in hearing 80 dB, 90 dB or more [0023], [0187], Figures 2 and 3, and further discloses a hearing loss at baseline affecting frequencies equal to or lower than 2000 Hz [0078]. Azasetron analogs of present claim 27 are taught in ‘167 claim 20. Hearing loss of present claim 21, is taught at [0024], the hearing loss being unilateral. Dosages of instant claims 28-30 are taught starting at [0136].
Wei et al. teaches various corticosteroids, such as methylprednisone commonly prescribed to treat ISSHL. Wei et al. discusses the use of combination agents including corticosteroids (see Description, page 3).
Regarding the combination of references, MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at ___, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Based on the teachings of the MPEP and KSR above, by employing the rationale in A, F, and G above, it would have been obvious for one of ordinary skill in the art to make the aforementioned modifications and arrive at the presently claimed invention. One of ordinary skill in the art would be motivated to administer the compounds of US20180207167 for the treatment of SSHL in combination of additional agents, such as, corticosteroids to arrive at the presently claimed invention.
If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See MPEP 2145.
Please note that if Applicant intends to rely on unexpected or unforeseen results, attention is invited to MPEP 716. Absent clear, convincing, side-by-side data demonstrating unobviousness vis-à-vis the prior art commensurate with the scope of protection sought, the claims are considered prima facie obviousness.Conclusion
15. No claims are allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Samantha Shterengarts whose telephone number is (571)270-5316. The examiner can normally be reached on Monday thru Thursday 9-6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Adam Milligan can be reached on 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
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