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 .
Claims status
Applicants reply filed 2/29/2026 is acknowledged.
Claims 2, 5 is/are cancelled. Claims 1, 3, 4, 6-18 is/are currently pending and is/are under examination.
Withdrawn Objections
The objections presented herein represent the full set of objections currently pending in this application. Any objections not specifically reiterated are hereby withdrawn.
Claim Objections
Claim 1 is objected to because of the following informalities: The use of the comma after the word animal in line 3 is grammatically incorrect. Removal of said comma is recommended. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) - Withdrawn
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.
Rejection of Claims 1-18 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of claim amendments and cancellations.
Claim Interpretation
Claims 9 and 10 are amended to recite “wherein steps (1) to (3) are carried out over a period of [..] weeks”. These claims do not require any specific method step of claim 1 to occur over any specific duration or over the entire duration, as long the entire method (i.e. steps (1) to (3)) takes place over the recited period. For example, the claimed method embraces a method wherein the animal is selected at the start of the period, the animal is exposed to hypoxia once or more for a few minutes to days anytime during the “period of […] weeks” and the animal is fed a high-fat diet or injected with galactose once or more for a few minutes to days anytime during the “period of […] weeks”. Thus, claims 9 and 10 are broadly interpreted to embrace a method wherein as long as the entire method occurs over the period of number of weeks recited in the claims, any step in this claim is not required to occur over the entire duration.
Claims 11-16 continue to recite intended results that flow from the active steps of claim 1 and thus the claim interpretation is reiterated. Claim 11 recites the types of hearing loss produced. Claim 12 recites “wherein the age-related hearing loss is expressed by one or more effects selected from the” recited list. The expression of age-related hearing loss i.e. outcomes of the model of age-related hearing loss, including the specifically recited types of claim 11, necessarily flows from the active steps of claim 1. Similarly, the genes expressed recited in claim 13 are the genes necessarily expressed by the animal model produced by the active steps of claim 1. Additional intended results such as the level of hearing loss (claim 14) and the duration of hearing loss (claim 15 and 16) are also results that flow from the active steps of claim 1. Regarding intended results, MPEP 2111.04 guides that "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, a prior art(s) that anticipates or renders obvious the method of claim 1, necessarily anticipates or renders obvious its intended results recited in claims 11-16.
Claim Rejections - 35 USC § 112(a) - Withdrawn
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.
Rejection of Claims 1-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is withdrawn in light of amendment to claim 1 that now recites specific rodent animal species.
Claim Rejections - 35 USC § 103 – New, necessitated by claim amendments
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.
Rejection of Claim(s) 1-4, 6, 9-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017) and Hwang et al (PLoS ONE 8(4): e60730. doi:10.1371/journal. pone.0060730, April 2013) in view of Fujimoto et al (Oxidative Medicine and Cellular Longevity, Vol. 2014, #582849) is withdrawn because claim 1 now requires galactose injection not taught by Seo or Hwang.
Rejection of Claim(s) 1-4, 7-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017), and Wu et al (PLoS ONE 7(11): e50483. doi:10.1371/journal. pone.0050483. November 2012) is withdrawn because claim 1 now requires HFD not taught by Seo or Wu.
Rejection of Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017) and Hwang et al (PLoS ONE 8(4): e60730. doi:10.1371/journal. pone.0060730, April 2013) in view of Fujimoto et al (Oxidative Medicine and Cellular Longevity, Vol. 2014, #582849) as applied to claim 1 above, and further in view of Wu et al (PLoS ONE 7(11): e50483. doi:10.1371/journal. pone.0050483. November 2012) is moot due to claim cancellation.
Rejection of Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017) and Hwang et al (PLoS ONE 8(4): e60730. doi:10.1371/journal. pone.0060730, April 2013) in view of Fujimoto et al (Oxidative Medicine and Cellular Longevity, Vol. 2014, #582849) as applied to claims 1, 17 above, or alternatively over Seo et al (SLEEP, Vol. 40, No. 9, 2017), and Wu et al (PLoS ONE 7(11): e50483. doi:10.1371/journal. pone.0050483. November 2012) ) as applied to claims 1, 17 above, and further in view of Frisina et al (Aging, Vol. 8, No. 9, Sep 2016) is withdrawn because previous rejection of claim 1 that this rejection depended from is now withdrawn.
Claim(s) 1, 3, 4, 6-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017), Hwang et al (PLoS ONE 8(4): e60730. doi:10.1371/journal. pone.0060730, April 2013) and Wu et al (PLoS ONE 7(11): e50483. doi:10.1371/journal. pone.0050483. November 2012) in view of Fujimoto et al (Oxidative Medicine and Cellular Longevity, Vol. 2014, #582849)/
The claimed method to produce an animal model for age-related hearing loss induces hearing loss in an animal by combining at least three conditions that are known to cause hearing loss and/or aging of the inner ear (hypoxia, HFD and galactose injection). As detailed below, Seo teaches a method to induce hearing loss in mice using intermittent hypoxia, Hwang induces hearing loss in mice using high fat diet and Wu teaches galactose injection to cause inner ear aging.
Regarding claims 1-4, Seo teaches a method that comprises selection of 8 week old mice (as required by claim 1) that have normal hearing (=claimed step (1); 8 week old mice are young and have not yet developed age-related hearing loss). These mice are subjected to chronic intermittent hypoxia by placing the mice in hypoxia chamber (=claimed step (2)) (Methods: Animals and Exposure to CIH). The mice were exposed to chronic intermittent hypoxia for 12 hours alternated with normoxia for 12 hours, wherein chronic intermittent hypoxia comprised exposing mice to 5% oxygen and normoxia comprised exposing mice to 21% oxygen (as required by claims 3-4; Methods: Animals and Exposure to CIH).
Seo teaches carrying out the method for 4 weeks during which mice developed hearing loss and extensive hair cell destruction which indicates a sensory presbycusis (as required by claims 9, 11; Methods: Animals and Exposure to CIH, Figure 1, 2). Seo’s method was effective at inducing hearing loss such that the hearing threshold were already above 30dB at 32kHz in just 4 weeks of hypoxia exposure and accompanied with hair cell destruction, oxidative stress and mitochondrial dysfunction (intended result recited in claims 12 and 14; Figure 1-5).
Regarding claims 1, 2, 6, Hwang teaches a method that comprises selection of 4 week old mice (as required by claim 1) that have normal hearing (=claimed step (1); 4 week old mice are young and have not yet developed age-related hearing loss) that are subjected to HFD (=claimed step (3)) (Materials and Methods: Animals, see Baseline measures in Table 1). The HFD used in AIN-93G which is mouse diet comprising vitamins in which the fat content was adjusted to 60% (as required by claim 6; Materials and Methods: Animals).
Hwang teaches carrying out the method for 16 weeks during which mice developed hearing loss and loss of SG neurons which indicates a neural presbycusis (as required by claims 9, 11; Table 2, 3). Hwang’s method was effective at inducing significant hearing loss in the 16 week HFD exposure such that the hearing threshold were above 30dB at each of the frequency tested (4, 8, 16, 32kHz) and accompanied by fat accumulation, oxidative stress represented by HIFa expression, accelerated aging (intended result recited in claims 12 and 14; Table 2, Figure 1).
Regarding claims 1, 7, 9, and 10, Wu teaches a method that comprises selection of 7-8 week old mice (as required by claim 1) that have normal hearing (=claimed step (1); 8 week old mice are young and have not yet developed age-related hearing loss) that are subjected to galactose injection (=claimed step (3)) (Materials and Methods: Animals and treatment). The galactose injection was at a dose of 800mg/kg or 1000mg/kg for a total of 10 weeks (as required by claim 7, 9, 10) (Materials and Methods: Animals and treatment).
Wu teaches that although there method did not result in hearing loss as measured by hearing threshold (Table 1), it induced oxidative stress as measured by SOD activity (Table 2), and mitochondrial dysfunction as measured by accumulation of mtDNA 3873-bp deletion (Figure 1) which are both indicators of accelerated aging including aging of the auditory system (Discussion, para 1 and last para) (intended result recited in claims 12). Wu also teaches that although galactose injection do not result in hearing loss but due to their effects on accelerating aging, it was known that D-galactose injection render the animals vulnerable to secondary perturbations such as by enhancing sensitivity to antibiotics that cause hearing loss (page 2, col. 1, para 1).
The combination of prior art cited above under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S., 82 USPQ2d 1385 (2007). Exemplary rationales that may support a conclusion of obviousness are in MPEP 2143.
In the present situation, rationale A (Combining prior art elements according to known methods to yield predictable results) is applicable. MPEP 2143 guides that for rationale A “Office personnel must articulate the following: 1) a finding that the prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference; (2) a finding that one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately; (3) a finding that one of ordinary skill in the art would have recognized that the results of the combination were predictable; and (4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness”.
(1) The prior art of Seo, Hwang and Wu teach the active steps of claims 1, 3, 4, 6, 7, 9, 10 and explicitly identify producing the intended results of claims 11, 12, 14. Seo taught use of intermittent hypoxia to produce hearing loss in mice. The parameters recited for intermittent hypoxia in claims 3 and 4 are also taught by Seo.
Hwang taught use of HFD to produce hearing loss in mice. The parameters recited for HFD in claim 6 are also taught by Hwang.
Wu taught use of D-galactose injection to produce inner ear aging in mice and the ability of D-galactose to enhance sensitivity to additional perturbations that cause hearing loss. The parameters recited for D-galactose injection in claim 7 are also taught by Wu.
(2) An ordinary artisan would combine these conditions wherein the intermittent hypoxia of Seo would result in oxidative stress and mitochondrial dysfunction leading to sensory presbycusis, the HFD of Hwang would result in fat accumulation and its sequelae such as oxidative stress and mitochondrial dysfunction leading to neural presbycusis, and D-galactose of Wu would also result in oxidative stress and mitochondrial dysfunction leading to accelerated aging in the inner ear which is expected to enhance the hearing loss effect of intermittent hypoxia of Seo. Such a combination would simply require substituting the normal diet of the mice exposed to Seo’s chronic intermittent hypoxia condition with Hwang’s HFD and injecting the mice with Wu’s D-galactose injection.
(3) Since both hypoxia and HFD are taught to induce hearing loss in mice, an ordinary artisan reasonably predicts that combining these conditions would also result in hearing loss. Furthermore, since D-galactose is taught to accelerate aging such that it enhances effects of hearing loss inducing agents, an ordinary artisan reasonably predicts that combining D-galactose with hypoxia and HFD would also result in hearing loss. Additionally, hypoxia and HFD were shown to result in hearing loss by targeting different cells types (hair cells in hypoxia and neurons in HFD), an artisan reasonably predicts that combining these conditions would also result in a more profound sensory and neural hearing loss. Similarly, since D-galactose is taught to accelerate aging such that it enhances effects of hearing loss inducing agents, an artisan reasonably predicts that combining including D-galactose would enhance the effects of hypoxia and/or HFD.
Therefore, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR. Therefore, it would be obvious to a person of ordinary skill in the art to combine the chronic intermittent hypoxia of Seo with HFD of Hwang and D-galactose of Wu to yield a predictable result of a method that produces hearing loss in mice. Such a combination would produce the animal of claim 17. Furthermore, such an animal would be considered an animal model for an age-related hearing loss because it recapitulates the oxidative stress and mitochondrial dysfunction associated with aging. as taught by Wu. Further, see teachings in “Putative Role of Oxidative Stress and Mitochondrial Dysfunction in ARHL” from Fujimoto that teaches that “The important role of oxidative stress and mitochondrial dysfunction in the development of ARHL has been established”. Such a combination could be reasonably made by simply substituting the normal diet of the mice exposed to Seo’s chronic intermittent hypoxia condition with Hwang’s HFD and injecting these mice with Wu’ D-galactose. An ordinary artisan would be motivated to combine these conditions in order to investigate if the combination would result in a more profound and/or long lasting hearing loss.
Regarding the dose of galactose recited in claim 8, Wu teaches a D-galactose dose of 800-1000 mg/kg. Wu does not teach galactose injection at a dose of 250-600mg/kg. However an ordinary artisan when combining Seo, Hwang and Wu’s method would use routine optimization to adjust the dose of D-galactose to achieve desired results. Wu teaches that both the lower dose of 800mg/kg and the higher dose of 1000mg/kg are effective at producing oxidative stress and mitochondrial dysfunction (Figures 1, 3, 4, 5). According to MPEP 2144.05 (II), “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")”. In the instant case, there is no evidence of record that the claimed dose (250-600mg/kg) is critical such that the difference in the dose of Wu (800-1000mg/kg) renders a patentable distinction. Furthermore, identifying an optimum dose, especially when combining methods of Seo, Hwang and Wu is routine. Therefore, in teaching a dose of 800-100mg/kg, Wu renders obvious the claimed dose.
Regarding the intended results of claims 11-16, Seo, Hwang and Wu explicitly identify producing the intended results of claims 11, 12, 14. Although Seo, Hwang and Wu do not identify the specific genes expressed in their animal models, as recited in claim 13 or if the hearing loss is maintained chronically, such as for 3 months or more, as recited in claims 15-16, the combination of Seo, Hwang and Wu teach each of the active steps of the claimed method. As noted above in the claim interpretation section, the intended results of claim 11-16 necessarily flow from these active steps. Furthermore, an ordinary artisan reasonably expects that the combination of Seo, Hwang and Wu that produces aging of the auditory system would also result in changes in the expression of the associated genes such as recited in claim 13. Similarly, an artisan would reasonably expect that the combination of Seo, Hwang and Wu would produce hearing loss that could be maintained chronically, such as for 3 months or more, as recited in claims 15-16, by simply optimizing the duration of the exposure to hypoxia and/or HFD. Such an optimization to achieve desired hearing loss would be considered routine.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (SLEEP, Vol. 40, No. 9, 2017), Hwang et al (PLoS ONE 8(4): e60730. doi:10.1371/journal. pone.0060730, April 2013) and Wu et al (PLoS ONE 7(11): e50483. doi:10.1371/journal. pone.0050483. November 2012) ) in view of Fujimoto et al (Oxidative Medicine and Cellular Longevity, Vol. 2014, #582849) as applied to claims 1, 17 above, and further in view of Frisina et al (Aging, Vol. 8, No. 9, Sep 2016).
Claim 18 is directed to a method of using the animal of claim 17 that is a model of age-related hearing loss produced by the method of claim 1.
The teachings of Seo, Hwang, Wu and Fujimoto as detailed in the U.S.C. 103 rejection of claim 1 and 17 over Seo, Hwang, Wu and Fujimoto above are relied upon in the instant rejection.
Seo, Hwang, Wu and Fujimoto teach the method of claim 1 that produces the animal of claim 17.
Seo, Hwang, Wu and Fujimoto do not teach a use of the animal produced by their respective methods in screening drugs for treatment and/or prevention of age-related hearing loss. However, use of animals that model a disease to screen for drugs that treat and/or prevent the disease is an obvious use of an animal model.
Frisina teaches use of mice that develop age-related hearing loss to test substances that could treat age-related hearing loss (Abstract). Frisina administered aldosterone, a drug candidate, to a mouse model of age-related hearing loss (=claimed step a) (Page 2082, col. 1, para 1; Material and Methods: Aldosterone hormone treatment implantation). Frisina measured hearing threshold in aged mice administered aldosterone and compared it to mice not administered aldosterone (= claimed step b) thus identifying aldosterone as a drug for age-related hearing loss because aldosterone reduced the hearing thresholds (= claimed step c) (Figure 1).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the mouse model of age-related hearing loss produced by Seo, Hwang, Wu and Fujimoto in drug screening method, such as taught by Frisina. An ordinary artisan would be motivated to use a mouse model of age-related hearing loss such as produced by Seo, Hwang, Wu and Fujimoto in drug screening method, such as taught by Frisina, because the mouse models of Seo, Hwang, Wu and Fujimoto could be produced faster since they accelerate aging and thus do not require waiting for the mouse aging process. An ordinary artisan would reasonably expect to use a mouse model of age-related hearing loss such as produced by Seo, Hwang, Wu and Fujimoto in drug screening method, such as taught by Frisina, by substituting the mice of Frisina with the mice produced by Seo, Hwang, Wu and Fujimoto.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in
the art at the effective time of filing of the invention, especially in the absence of evidence to the
contrary.
Response to Arguments
Applicant’s arguments with respect to the U.S.C. 103 rejections of Claim(s) 1-4, 6, 9-17 over Seo, Hwang and Fujimoto or Claims 1-4, 7-17 over Seo and Wu or Claims 18 over Seo, Hwang, Fujimoto or Seo, Wu, further in view of Frisina (page 10) have been considered but are moot because the new ground of rejection necessitated by claim amendments.
Arguments pertinent to instant U.S.C. 103 rejection of Claims 1, 3, 4, 5-17 over Seo, Hwang, Wu and Fujimoto and Claim 18 over Seo, Hwang, Wu and Fujimoto further in view of Frisina are addressed below.
Applicant argue that “Seo and Hwang disclose only methods in which a single condition is applied-specifically, either intermittent hypoxia alone or provision of a high-fat diet alone-and fail to disclose or suggest applying these conditions in combination with each other” (page 11, para 2) and “Wu merely discloses that galactose injection induces aging-related changes in the inner ear of mice. It does not at all disclose or suggest applying intermittent hypoxia and/or provision of a high-fat diet in combination with galactose injection” (page 11, para 4).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The combination of Seo, Hwang and Wu together teach the combination.
Applicant argue that the claimed method provide unexpected results pointing to Figures 6b, 9i and 11 (page 12).
In response, first it must be noted that the legend of the conditions provided on page 11 is incorrect. Table 1 in the specification provide the correct legend; also show in Figure 3a and 3b. G1 is control, G5 is hypoxia only condition and G8 is the claimed triple combination.
Regarding Figure 6b, it does not compare the G8 condition with any other condition such that it could be concluded that “it was confirmed that the hearing threshold of Group G8 increased to the greatest extent” as the Applicant alleges (page 12, para 1). A comparison of conditions is shown in Figure 9a-c wherein G7 (Hypoxia+HFD) appears to perform the same as G8 in both Figure 9b and 9c. The inference provided in the specification is “it has been confirmed that there is no significant change in the hearing threshold in GI (G2), HFD (G3) and GI + HFD (G4) (see a and b of FIG. 9) and the hearing threshold has increased within 2 months under the dual condition of HFD + hypoxia (G7) (see b and c of FIG. 9). In addition, it has been confirmed that the hearing threshold has increased after 2 months when hypoxic condition is included (G5 to G8), and it has been thus confirmed that a hypoxic condition and a HFD condition significantly affect the increase in hearing threshold (see a to c of FIG. 9). In conclusion, it has been confirmed that the most effective method for changing the hearing threshold is a hypoxic condition, and that a synergy effect is exhibited when HFD is fed and/or galactose is injected in hypoxia.” (emphasis added; page 34). Thus, Applicants themselves conclude that hypoxia is the key means of inducing hearing loss, already shown by Seo and that either HFD or GI could be included.
Regarding Figure 9i, it compares percent survival of OHC and IHC over time. Again it does not provide a statistical comparison across conditions such that it could be concluded that “the triple-condition group exhibited the greatest reduction in survival rate” as the Applicant alleges (page 12, para 2). It appears that the survival rate of Hypoxia + HFD (G7) is not statistically different from the claimed triple condition (G8). The inference provided in the specification is “In particular, it has been confirmed that damage to OHC is severe under the dual and triple conditions (i to k of FIG. 9). It has been confirmed that the survival rate of hair cells is 80% or more under the single condition of HFD or GI and the survival rate is 50% or more under the dual condition of HFD and GI, but the survival rate decreases to less than 20% when a hypoxic condition is included, and it has been thus confirmed that oxidative stress caused by hypoxia damages hair cells and causes hearing loss.” (emphasis added; page 35). Thus, Applicants themselves conclude that hypoxia is the key means of inducing hearing loss, already shown by Seo and that either HFD or GI could be included.
Regarding Figure 11, it compares expression of various genes that are disclosed as associated with aging or damage in the liver, kidney and cochlea (page 28, para 1). This data is not limited to markers of aging or even markers from cochlea. The samples were collected from liver and kidney, in addition to cochlea as evidenced by Applicants NPL (see 4.9. Real-Time PCR in Park et al; IJMS 2020IDS 1/17/2023). Thus relevance of this data to establish unexpected results for a claim directed to age-related hearing loss is not established. Furthermore, the changes in gene expressions shown in Figure 11 are an inherent outcome of a method with the claimed active steps. It is these active steps that are rendered obvious by the combination of the references. Evidence of these alleged unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention and where these alleged unexpected properties of the claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness; see MPEP 716.02(c). Herein, as detailed above, Applicants own disclosure supports that hypoxia is the primary driver in their hearing loss model and the claimed triple condition does not result in an animal model with unexpected or superior hearing loss. As noted in the rejection above, since both, hypoxia and HFD were shown to result in hearing loss by targeting different cells types (hair cells in hypoxia and neurons in HFD), an artisan reasonably predicts that combining these conditions would also result in a more profound sensory and neural hearing loss. Similarly, since D-galactose is taught to accelerate aging such that it enhances effects of hearing loss inducing agents, an artisan reasonably predicts that combining including D-galactose would enhance the effects of hypoxia and/or HFD. Thus, the expectation in the art was that the combination should increase the hearing loss produced by hypoxia. The data regarding aging or damage related genes from liver, kidney and cochlea do not outweigh these teachings from the specification and the art.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
Prosecution Insights