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 .
Notice of Non-Compliant Amendment (37 CFR 1.121)- Withdrawn
The Notice of Non-Compliant Amendment is overcome by the presentation of claim 1 so that claim 1 recites the entire claim text in the previous claim 1 (10/28/2024 claim set), and is hereby withdrawn.
Status of the Claims
Claims 1, 10-12, 14, 16-18, 21 and 78-80 are pending.
Applicants’ arguments filed on 02/27/2025, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments filed on 02/27/2025, have been fully considered. Applicants have newly added claims 80. Claims 16 and 18 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected species. Therefore, claims 1, 10-12, 14, 17, 19-25 and 78-80 are subject of the Office Action below.
Maintained Rejections
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 1, 10-12, 14, 17, 21 and 78-79, is maintained and newly added claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang of record (Investigative Ophthalmology & Visual Science, 2004) in view of Szczesniak of record (J. Ocular Pharmacology and Therapeutic, 2011), for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
Independent claim 1 is directed to a method of treating light-induced retinal degeneration in a subject in need thereof, with a therapeutically effective amount of a compound of formula (II):
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or a pharmaceutically acceptable salt, tautomer, or solvate thereof.
Claim 1 does not specify a particular amount for a compound of formula (II), but it does reads on an amount of a compound of formula (II). Accordingly, for the purpose of examination, any amount of a compound of formula (II), that is employed in order to elicit the desired biological response, in included in the interpretation of “a therapeutically effective amount”.
By way of a background, Applicants’ invention (see specification at, for example, ¶s 0011-0012 and 0023), is directed to a method for treating ocular disorders such as light-induced retinal degeneration, with a compound of formula (II). The specification discloses that, treatment of mice with abnormal cannabidiol (abn-CBD):
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, followed by induction of retinal degeneration via exposing the mice to light, was found to protect the mice against light-induced retinal degeneration. Please see ¶s 0034-00135, 00153, 00172 and Figure 8.
Similar to the Applicants’ invention (see discussions above), Zhang teaches that microglia-activated neurotoxicity, played a significant role in the pathogenesis of light-induced retinal degeneration. Specifically, treatment of mice with a microglia inhibitor (minocycline, not the abn-CBD of the claimed invention), followed by induction of retinal degeneration via exposing the mice to light, was found to result in the protection of mice against light-induced retinal degeneration. Please see abstract, Figures 1-6, Table 1 and discussions therein.
Accordingly, at the time of the instant invention, a person skilled in the art would have envisioned a method of treating light-induced retinal degeneration with a microglia inhibitor, in the Zhang disclosure.
Although Zhang is not explicit in teaching use of abn-CBD, a person skilled in the art would have had a reasonable expectation of success in employing abn-CBD as a therapeutic option for light-induced retinal degeneration.
This is because at the time of the instant invention, it was known in the art that abn-CBD can inhibit microglia activated neurotoxicity. For example, Szczesniak states:
“Although abn-CBD and CBG-DMH have not yet been fully investigated for their neuroprotective potential in models of retinal neurodegeneration, abn-CBD has been reported to increase RGC survival and inhibit activated retinal microglia after axotomy76. In other studies, abn-CBD was shown to interact with abn-CBD-sensitive receptors on microglial cells in an organotypic hippocampal slice culture, after excitotoxic shock induced by N-methyl-D-aspartic acid (NMDA), to reduce microglial cell activation and neuronal degeneration77.” Emphasis added. Please see page 433, 2nd ¶ on left column.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to administer a microglia inhibitor (e.g., abn-CBD of Szczesniak), to a subject suffering from light-induced retinal degeneration, with a reasonable expectation of treating light-induced retinal degeneration in the subject.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
The skilled artisan would have found it obvious to substitute one known element (a microglia inhibitor of Szczesniak, i.e., abn-CBD) for another (i.e., a microglia inhibitor of Zhang), for the predictable result of treating a subject in need of a treatment for light-induced retinal degeneration (Zhang).
The use of simple substitution of one known element for another to obtain predictable results as a requirement of a prima facie case of obviousness has been deemed as proper (please see MPEP § 2143). In the instant case, the one known element is a microglia inhibitor and the predictable results is treating an ocular disorder associated with microglia-activated neurotoxicity (e.g., light-induced retinal degeneration), in which the therapeutic intervention is at a microglia inhibition. It is therefore reasonable to conclude that the strength of correlation between the inhibition of microglia and treating an ocular disorder associated with microglia-activated neurotoxicity (e.g., light-induced retinal degeneration), gives rise to a reasonable expectation of success.
Therefore, claim 1 is obvious over Zhang and Szczesniak.
Regarding claims 10-12, 14, 17, 21 and 78-79, Szczesniak teaches abn-CBD (recited in claim 17, i.e., Applicants’ elected compound, see page 7 of Remarks filed on 09/26/2023). Please see discussions above.
Regarding claim 80, each of Zhang (see abstract) and Szczesniak (see abstract), teaches intraperitoneal injection.
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Response to the Applicants’ Arguments
Applicants raised several arguments (see pages 6-13 of Remarks), alleging that the instant claims are non-obvious over the cited references on the grounds that:
1) the cited references do not combine to suggest or teach the claimed invention (see pages 6-8 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive. The reasons for the Office’s reliance on the cited references in order to reject the instant claims are set forth in the previous Office action and reiterated above. The Examiner, therefore, applies the same reasons hereto.
2) Szczesniak cannot be employed to correct the deficiency in the teachings of Zhang because Szczesniak fails disclose:
a) treating light-induced retinal degeneration with abn-CBD (see page 8 of Remarks) and
b) that abn-CBD can cross the BBB citing Zhang, who requires ability to cross the BBB as a requirement (see pages 8-11 of Remarks)
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive.
This is because:
2a) Zhang teaches inhibition of microglia as a therapeutic option for treating light-induced retinal degeneration, but did not disclose abn-CBD as an inhibitor of microglia (see discussions above). Szczesniak was cited for disclosing abn-CBD as an inhibitor of microglia (see discussions above). The Office did not take a position that Szczesniak teaches treating light-induced retinal degeneration with abn-CBD.
2b) Although Szczesniak is not explicit in disclosing that abn-CBD can cross the BBB, at the time of the instant invention, cannabinoids (CBDs), including abn-CBD, were known in the art as highly lipophilic compounds, and CBDs have been known to cross the BBB. For example:
i) Mo et al (Eur J. Pharmacology, 2004, 489, 21-27, cited in response to the Applicant’s allegations) on page 24, states: “Cannabinoids including abn-CBD are highly lipophilic”.
ii) Deiana et al (Psychopharmacology, 2012, 219, 859-873, cited in response to the Applicant’s allegations) on page 870, states: “Given their lipophilicity, all tested phytocannabinoids crossed the BBB showing consistent brain penetration”. Phytocannabinoids include CBD (see Deiana et al at Figure 1).
Accordingly, at the time of the instant invention, a person skilled in the art would have had a reasonable expectation that similar to highly lipophilic CBD, highly lipophilic abn-CBD would cross the BBB showing consistent brain penetration.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Furthermore, in response to the Applicants’ arguments against the references individually (e.g., Szczesniak fails to teach treating light-induced retinal degeneration with abn-CBD (see page 8 of Remarks)), one cannot show nonobviousness by attacking references individually where the rejections are based on combination of references. In obviousness rejection a combination of references is used, and the references are relied upon in combination and are not meant to be considered separately as in a vacuum. It is the combination of all of the cited and relied upon references that make up the state of the art with regard to the claimed invention. 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).
3) at the time of the instant invention, the safety of administering abn-CBD to a subject has not been established and the question of whether abn-CBD interacts specifically with CRBP1 or CRBP2, had not been answered (see pages 11-12 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive.
This is because:
i) Szczesniak teaches administering abn-CBD to a subject without reporting any safety issues (see discussions above).
ii) the Zhang reference did not require interaction of an inhibitor of microglia (e.g., abn-CBD) with CRBP1 or CRBP2, as a requirement for treating light-induced retinal degeneration. Furthermore, the lack of toxicity and inability of abn-CBD to interfere with, for example CRBP2 activity (see pages 11-12 of Remarks), is a property of abn-CBD. Since Szczesniak discloses abn-CBD as an inhibitor of microglia (see discussions above), the abn-CBD of Szczesniak must necessarily exhibit disclosed utility.
An inherent characteristic may “be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan.” Endo Pharm. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374, 1381 (Fed. Cir. 2018).
Conclusion
No claim is allowable.
THIS ACTION IS MADE FINAL. 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.
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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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