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 .
DETAILED ACTION
Response to Amendment
The Information Disclosure Statement (IDS) filed 8 December 2025 has been entered. Applicant’s submission of the replacement drawings filed 8 December 2025 is acknowledged. Applicant’s amendments of the abstract, specification, and claims filed 8 December 2025 have been entered. Applicant’s remarks filed 8 December 2025 are acknowledged.
Claims 1-18 are pending. Claims 5-11 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 1-4 and 12-17 are under examination.
Sequence Rules Compliance
Applicant has amended the drawings (Figure 21) to add sequence identifiers (SEQ ID NOs) for each of the recited sequences. The instant application is now in compliance with the sequence rules, 37 CFR 1.821-1,825.
Specification
The objection to the abstract is withdrawn in response to Applicant’s amendment of the abstract.
Claim Rejections Withdrawn
The rejection of claims 1, 3-4 and 12-17 under 35 U.S.C. 102(a)(1), as being anticipated by Gao et al. (US 2007/0054360 A1, Pub. Date: Mar. 8, 2007), is withdrawn in response to Applicant’s amendment of independent claim 1 to require that the substance is a specific binding substance for CD96 which is an anti-CD96 antibody or a fragment thereof that inhibits the binding of CD96 to CD155 and that inhibits or reduces CD96 signal transduction.
Claim Rejections Maintained
Claim Rejections - 35 USC § 112
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.
Amended claims 1-4 and 12-17 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
Applicant argues that the specification discloses a representative number of anti-CD96 antibodies, e.g., TX111.2 (an anti-mouse CD96 neutralizing antibody) and NK92.39 (an anti-human CD96 neutralizing antibody), and the specification discloses that these two antibodies, despite targeting CD96 of different species, demonstrate (i) inhibition of CD96 binding to CD155, (ii) inhibition of CD96 signaling, (iii) suppression of IL-17 production, and (iv) therapeutic efficacy in disease models. Applicant argues that the claims, as presently amended, specify (i) the type of substance (i.e., a specific binding substance for CD96 or a CD96 expression inhibitor) and (ii) the functional mechanism (i.e., CD96 signal inhibition), and that the combination of structural and functional features ensure compliance with the written description requirement. Applicant further argues that the experimental data with CD96-deficient mice demonstrate that regardless of structural form, the functional feature (e.g., suppression of CD96 signaling) leads to the biological effects (e.g., suppression of immune responses of IL-17-producing cells, and therapeutic efficacy for diseases, such as psoriasis), and such mechanistic validation provides structure-independent functional correlation, supporting the claimed genus defined by inhibition of CD96 signaling, rather than by any particular antibody structure.
Applicant’s arguments have been fully considered but have not been found to be persuasive.
Amended claim 1 now recites:
“A method of treating a disease or a pathological condition involving an immune response of an IL-17-producing cell, the method comprising:
administering an effective amount of a substance that inhibits the binding of CD96 to at least one protein selected from CD155 and CD111 to a subject having the disease or the pathological condition,
wherein the substance is a specific binding substance for CD96 or a CD96 expression inhibitor,
wherein the specific binding substance for CD96 is an anti-CD96 antibody or a fragment thereof that inhibits the binding of CD96 to CD155 and that inhibits or reduces CD96 signal transduction,
wherein the CD96 expression inhibitor is siRNA, shRNA, miRNA, ribozymes, or an antisense nucleic acid, wherein the CD96 expression inhibitor reduces CD96 expression and inhibits the binding of CD96 to CD155 to inhibit or reduce CD96 signal transduction,
wherein inhibiting or reducing CD96 signal transduction functions as an immune response suppressant for the IL-17-producing cell thereby suppressing IL-17 production or IL-17- mediated immune responses of the IL-17-producing cell.”
The specification fails to provide adequate written description and evidence of possession of the claimed substances, i.e., the specific binding substances for CD96 or the CD96 expression inhibitors, which exhibit the activities of, e.g., inhibiting the binding of CD96 to CD155 and inhibiting or reducing CD96 signal transduction. The two antibodies (the anti-mouse CD96 antibody TX111.2 and the anti-human CD96 antibody NK92.39) are not sufficient to represent the genus of the anti-CD96 antibodies. It is well established in the art that monoclonal antibodies that bind to the same epitope have dissimilar binding site structures. Even up to date, one skilled in the art still cannot predict the structures of the antibodies that bind to a disclosed epitope, let alone the antibodies having particular properties/activities. While the specification discloses that the antibodies TX111.2 and NK92.39 exhibit the activities required by the present claims, e.g., inhibiting the binding of CD96 to CD155 and inhibiting or reducing CD96 signal transduction, and one skilled in the art would expect that anti-CD96 antibodies comprising light chain CDR1-3 set forth in SEQ ID NOs: 14-16 and heavy chain CDR1-3 set forth in SEQ ID NOs: 17-19 would also exhibit such properties/activities, however, there is no evidence that any anti-CD96 antibody would have such properties/activities. For example, Aguilera et al. (Oncoimmunology, 2018 Feb 1, Vol. 7(5): e1424677) (cited previously) teaches that the commercial anti-CD96 antibody “mAb 8B10” does not block CD96 binding to CD155 (see abstract). Clearly, the specification does not provide adequate written description for the structures (e.g., the heavy chain and light chain CDRs or the variable domains) of the anti-CD96 antibodies that inhibit the binding of CD96 to CD155 and reducing CD96 signal transduction. In the absence of sufficient description of distinguishing identifying characteristics, the skilled artisan cannot envision the detailed structures of the encompassed anti-CD96 antibodies as claimed.
Regarding the claimed CD96 expression inhibitors, the claims encompass siRNA, shRNA, miRNA, ribozymes, or antisense nucleic acid derived from any molecules that directly or indirectly affect CD96 expression (e.g., an siRNA that prevents synthesis of a transcription factor). The specification does not describe the structural characteristics of these molecules, nor teaches the correlation of structure to function.
Applicant argues that the claimed genus is defined by function (inhibition of CD96 signaling), rather than by any particular antibody structure, however, Applicant does not demonstrate possession of the genus, and there is no representative number of species or common structural features allowing a skilled artisan to visualize the full scope. Adequate written description requires more than a mere statement that is part of the invention and reference to a method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
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.
Amended claims 1-4 and 15-16 remain rejected under 35 U.S.C. 102(a)(1), as being anticipated by Smythe (US 2016/0200814 A1, Pub. Date: Jul. 14, 2016).
Ground of Rejection
Smythe teaches a method of reducing or relieving immune inhibition, or facilitating treatment of a disease or condition, such as cancers or viral infections, in a mammal, said method including the step of at least partly inhibiting or reducing CD96 activity in one or more cells of the mammal to thereby enhance or restore immune surveillance in the mammal [0006] [0007] [0010]. Smythe teaches that the step of inhibiting or reducing CD96 activity in the mammal includes inhibiting or reducing CD96 binding to CD155 by using an antibody or antibody fragment that binds to CD96 [0008] [0045]. Smythe teaches using the method for treating cancers, including skin cancer [0055], or viral infections, such as HIV infection [0054]. Smythe teaches that compositions comprising the CD96-inhibitory agent may be administered via intravenous or intraperitoneal route [0064]. Smythe teaches that suitable dosages of CD96-inhibitory agents, alone or together with other therapeutic agents, for mammalian administration, including human administration, may be readily determined by persons skilled in the art [0059]. Therefore, Smythe anticipates the instant claims.
Response to Applicant’s Arguments
Applicant argues that Smythe does not disclose any IL-17-producing cell, nor does Smythe teach treatment of a disease or a pathological condition involving an immune response of an IL-17-producing cell by inhibiting CD96 activity. Applicant argues that the effects obtained by CD96 inhibition are opposite between Smythe and the present invention; in Smythe, CD96 is recognized as an immunosuppressive receptor on NK cells and CD96 inhibition would activate immunity, thereby treating cancers or viral infections; in the present invention, CD96 functions as an activating receptor in IL-17-producing cells, and neutralizing antibodies against CD96 (or other inhibitors) can suppress the immune response in IL-17-producing cells to thereby treat diseases involving these cells. Applicant argues that Smythe's therapeutic targets are limited to cancers and viral infections, and there is no mention of psoriasis or other disease involving an immune response of an IL-17-producing cell.
Applicant’s arguments have been fully considered but have not been found to be persuasive.
Independent claim 1 recites, inter alios, a method of treating a disease or a pathological condition involving an immune response of an IL-17-producing cell, the method comprising: administering an effective amount of a substance that inhibits the binding of CD96 to at least one protein selected from CD155 and CD111 to a subject having the disease or the pathological condition, wherein the substance is a specific binding substance for CD96 or a CD96 expression inhibitor, wherein the specific binding substance for CD96 is an anti-CD96 antibody or a fragment thereof that inhibits the binding of CD96 to CD155 and that inhibits or reduces CD96 signal transduction.
Smythe teaches methods for treating cancers, including skin cancer, or viral infections, e.g., HIV infection, by using an antibody or antibody fragment that binds to, and inhibits the activity of, CD96, wherein the antibody or antibody fragment inhibits CD96 binding to CD155 in one or more cells of the mammal. According to the instant specification, the disease or the pathological condition involving the immune response of an IL-17-producing cell is psoriasis, rheumatoid arthritis, atopic dermatitis, multiple sclerosis, cerebral infarction, nephritis, lung injury, pulmonary fibrosis or skin tumor. Thus, Smythe teaches using the same therapeutic agent to treat the same patient as the instant claims. With regard to the underlying mechanisms (e.g., suppression of immune response of the IL-17-producing cells), such would reasonably be considered to be inherent. A compound and all of its properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966)).
Therefore, Smythe anticipates the instant claims.
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.
Claims 14 and 17 remain rejected under 35 U.S.C. 103 as being unpatentable over Smythe (US 2016/0200814 A1).
Applicant provides the same arguments with regard to Smythe, which have been addressed above (see the 102 section). Smythe teaches as set forth above. Smythe, however, does not teach wherein the subject is administered 0.5-50 mg of the substance per kilogram (kg) of body weight in a single dose, and the subject is administered the substance once to several times a day (claims 14, 17). Given that the level of skill in this art is very high, and that optimizing parameters, such as the dosage and administration frequency, is routine, modifying the dosage and administration frequency of the anti-CD96 antibody used by Smythe to the claimed ranges/frequencies would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, with a reasonable expectation of success, absent evidence of unexpected results. As was found in In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
New Grounds of Objections/Rejections
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.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Smythe (US 2016/0200814 A1, Pub. Date: Jul. 14, 2016) (reference provided previously), as applied to claims 1-4 and 15-16 above, and further in view of Morar et al. (Lancet Infect. Dis., 2010, Vol. 10(7): 470-478).
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.
Smythe teaches as set forth above. Smythe, however, does not teach treating a subject having psoriasis (claims 12-13).
Morar teaches the association between psoriasis and HIV infection. Morar teaches that the development of HIV-associated psoriasis and HIV-associated psoriatic arthritis might be associated with poor prognosis in untreated patients (see Abstract; and p. 470, col. 2, under section “HIV and psoriasis”). Morar teaches that the management of moderate and severe HIV-associated psoriasis is challenging, although patients typically improve with highly active antiretroviral therapy. Morar teaches that new biological treatments in this setting are promising (see Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Smythe to treat patients having HIV-associated psoriasis. One of ordinary skill in the art would have been motivated to do so, because Smythe teaches methods for treating viral infections (e.g., HIV infection) by using an antibody or antibody fragment that binds to, and inhibits the activity of, CD96, and Morar teaches that anti-viral therapy can improve patients having HIV-associated psoriasis. Therefore, the combined teachings provide a reasonable expectation of success in treating the patients.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is 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.
Claim 1 recites “a substance that inhibits the binding of CD96 to at least one protein selected from CD155 and CD111”, and the claim also recites “wherein the specific binding substance for CD96 is an anti-CD96 antibody or a fragment thereof that inhibits the binding of CD96 to CD155” and “wherein the CD96 expression inhibitor reduces CD96 expression and inhibits the binding of CD96 to CD155”. The claim recites a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim), which may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, the word “and” should be added at the end of the phrase “wherein the CD96 expression inhibitor reduces CD96 expression and inhibits the binding of …”.
Appropriate correction is required.
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 Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674