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 .
Claim Status
Claims 6-8, 16-20, and 25 have been cancelled and claims 1-5, 9-10, 15, and 21 have been amended, as requested in the amendment filed on 05/20/2026. Following the amendment, claims 1-5, 9-15, 21-24, and 26 are pending in the instant application.
Claims 11-14 and 22-24 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention in the Response filed 12/11/2025, there being no allowable generic or linking claim.
Claims 1-5, 9-10, 15, 21, and 26 are under examination in the instant office action.
Drawings - Objection Withdrawn
Applicant has submitted a replacement drawing sheet for Figure 6C wherein the figure is more legible. As such, the objection to the drawing is withdrawn.
Specification - Objections Withdrawn
The abstract of the specification was objected to for being less than 50 words in length. Applicant has submitted an amended abstract that is between 50 and 150 words in length. As such, the objection to the abstract of the specification is withdrawn.
The specification was further objected to for the use of trade names and marks used in commerce. Applicant has amended the specification such that the trade names and marks used in commerce are properly represented. As such, the objection to the specification is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
Claim 21 was rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for failing to comply with the written description requirement. It is noted that claim 21 has been amended such that the claim is now drawn to the antibody or epitope binding fragment according to claim 1, wherein said antibody has the heavy and light chain of mAb 20-10, wherein the heavy chain sequence is SEQ ID NO: 14 and the light chain sequence is SEQ ID NO: 2; the antibody or epitope binding fragment of amended claim 21 comprising the above-recited full length heavy and light chain sequences corresponding to instant SEQ ID NOs: 14 and 2, respectively, is adequately described in the instant specification. Thus, the rejection of claim 21 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for failing to comply with the written description requirement is withdrawn.
Claims 1-5, 9-10, 15, and 21 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement. Applicant has amended claims 1-5 and 9-10 to remove any recitation of fully human antibodies; subsequently dependent claim 21 no longer refers to/includes fully human antibodies. Furthermore, claim 15 has been amended such that the claim is now clearly in independent form and therefore does not refer to fully human antibodies. In view of the instant claim amendments, claims 1-5, 9-10, 15, and 21 are considered to be enabled. As such, the rejection of claims 1-5, 9-10, 15, and 21 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement is withdrawn.
Claims 5, 15, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite. Claim 5 has been amended to remove all trademarks/trade names. Claim 15 has been amended to recite “[a]n antigen binding fragment comprising…” and as such is now clearly in independent form. Claim 21 has been amended to remove the recitation of “FR1/CDR1/FR2/CDR2/FR3CDR3/FR4 sequence combination” and clearly recite the exact heavy and light chain combination corresponding to mAb 20-10 by their respective sequences. In view of the instant claim amendments, the rejection of claims 5, 15, and 21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
Claim Objections - New as Necessitated by Amendment
Claim 1 is objected to for the following minor informalities: the claim recites “light chain variable region CRDs…” at lines 4-5, but should read “light chain carriable region CDRs…”. Appropriate correction required.
Claim 21 is objected to for the following informalities: the claim recites “said antibody has the the heavy and light chain…” at lines 2-3, but should read “said antibody has the heavy and light chain…”. Appropriate correction required.
Claim Rejections - 35 USC § 112 - Maintained
Claim 26 stands as rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement. As detailed in the previous Office Action (02/20/2026) the specification, while being enabling for the treatment of an autoimmune disease, does not reasonably provide enablement for preventing an autoimmune diseases. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with the claim.
Applicant has provided no specific arguments against the rejection of claim 26 regarding scope of enablement. It is noted that Applicant asserts on Page 8 of Remarks (05/20/2026) that claim 26 has been amended to remove prevention of an autoimmune disease. No such amendment has been made, and as such the rejection of claim 26 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement is maintained.
Claim Rejections - 35 USC § 112 - Maintained, Updated as Necessitated by Amendment
Claims 1-5, 9-10, 15, and 26 stand as 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
Claims 1-5, 9-10, and 26 are all generally drawn to an antibody or antibody construct that binds to an epitope, or a fragment of said epitope that specifically or preferentially binds to human IDO2, said antibody or construct comprising heavy chain variable region CDRs of SEQ ID NOs: 16, 18, or 20 and light chain variable region CDRs of SEQ ID NO: 4, Gly-Ile-Ser, and SEQ ID NO: 7. Thus, the claims identify the antibody or antigen binding fragment by the function of binding human IDO2, and a partial sequence structure that comprises at least one of the recited heavy chain variable region CDRs of SEQ ID NO: 16, 18, or 20 and three light chain variable region CDRs of SEQ ID NO: 4, Gly-Ile-Ser, and SEQ ID NO: 7. It is further noted that as currently amended, it is unclear as to how the recited heavy chain variable CDR and light chain variable CDR sequences are organized within the antibody; it is unclear as to which sequences correspond to heavy chain variable CDR1, CDR2, and CDR3 and which sequences correspond to light chain variable CDR1, CDR2, and CDR3. Thus, the claims encompass a vast genus of antibody variants comprising as few as one of the recited heavy chain CDRs, and CDRs having varied positions in the antibody, construct, or fragment thereof.
Claim 15 is drawn to an antigen binding fragment comprising three heavy chain CDRs having the amino acid sequences SEQ ID NOs: 16, 18, and 20 and three light chain CDRs having the amino acid sequences SEQ ID NO: 4, 7, and the sequence GIS. It is noted that as currently amended, it is unclear as to how the recited heavy chain variable CDR and light chain variable CDR sequences are organized within the antigen binding fragment; it is unclear as to which sequences correspond to heavy chain variable CDR1, CDR2, and CDR3 and which sequences correspond to light chain variable CDR1, CDR2, and CDR3. Thus, the claims encompass a vast genus of antigen binding fragment variants comprising CDRs having varied positions in the antigen binding fragment.
The instant specification discloses three structurally similar anti-IDO2 antibodies at Pages 29-31 of the instant specification; said antibodies are identified as mAb 13-3, mAb 18-1, and mAb 20-10. It is specifically noted that these antibodies are defined by their full-length heavy and light chain sequences, which comprise HCDRs 1-3 and LCDRs 1-3, respectively. Notably, said HCDRs 1-3 correspond to SEQ ID NOs: 16, 18, and 20, respectively, and the LCDRs correspond to SEQ ID NOs: 4, 7, and the sequence GIS wherein the order of the LCDRs differs between the antibody species. It is specifically noted that for the instantly elected antibody species mAb 20-10, HCDRs 1-3 correspond to SEQ ID NOs: 16, 18, and 20, respectively, and the LCDRs 1-3 correspond to SEQ ID NO: 4, sequence GIS, and SEQ ID NO: 7, respectively. The instant specification discloses making three structurally similar antibodies and describes the complete HCDR 1-3, LCDR 1-3, full heavy chain, and full light chain sequences that all function to bind human IDO-2. The specification fails to disclose any other antibodies, antibody constructs, or antibody fragments thereof that comprise as few as one HCDR, comprise different CDR sequences than those recited above, comprise the recited HCDRs in a different order than that recited above that possess the function of binding to human IDO2.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30).
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants that function to bind human IDO2, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the antibody function, “specifically or preferentially binds human IDO2”, and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the antibodies identified as mAb 13-3, mAb 18-1, and mAb 20-10 disclosed at Pages 29-31 of the instant specification, the specification fails to provide any single heavy chain CDR structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequence variants for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
The claims broadly encompass any antibody that comprises at least one HCDR corresponding to SEQ ID NOs: 16, 18, or 20, wherein said CDRs as instantly claimed may be in any structural order, that functions to bind human IDO2. Applicants have not established any reasonable structure-function correlation with regards to the sequences of a single heavy chain CDR that, regardless of the other CDR sequences and/or the positions of the CDR sequences in the antibody, construct, or fragment thereof, will maintain human IDO2 binding function. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single human IDO2-binding antibody comprising at least one of the recited heavy chain CDR structures to the structure of any variants required to bind human IDO2 as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind human IDO2 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The IDO2 antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the CDRs that provide human IDO2-binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody variants that comprise as few as one of the recited heavy chain CDRs, wherein the heavy chain CDRs may be in variable orders structurally within the antibody, construct, or fragment thereof that retain the ability to bind human IDO2 that is required to practice the claimed invention.
Examiner Suggestion: Amend the claims to recite and require the antibody or antigen binding fragments to comprise, at minimum, all three CDR SEQ ID NOs from the heavy chain and all three CDR SEQ ID NOs from the light chain, which are the shared, critical sequence structures for IDO2 binding function of the claimed genus. Further amend the claims to indicate which CDR sequences correspond to HCDR positions 1-3 and LCDR positions 1-3 such that each antibody species is clearly defined by a set of six CDRs.
Claim Rejections - 35 USC § 112 - New as Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As currently amended, claim 4 fails to further limit the subject matter of claim 1 from which it depends. As amended, claim 4 recites the recombinant, synthetic, or monoclonal antibody or antibody construct according to claim 1 wherein said antibody is, for example, “a antibody” (see line 3). This limitation fails to further limit the recombinant, synthetic, or monoclonal antibody or antibody construct according to claim 1, and as such claim 4 is of improper dependent form. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Art-Free Subject Matter
It is noted that full-length HCDRs 1-3 corresponding to SEQ ID NOs: 16, 18, and 20, respectively, full-length LCDRs 1-3 corresponding to SEQ ID NO: 4, the sequence GIS, and SEQ ID NO: 7, respectively, full-length heavy chain variable region corresponding to SEQ ID NO: 14, and full-length light chain variable region corresponding to SEQ ID NO: 2 have been thoroughly searched and are free of the prior art. However, it is noted that the claims suffer from deficiencies under 35 U.S.C. 112(a) as described above.
Conclusion
Claims 1-5, 9-15, 21-24, and 26 are pending. Claims 11-14 and 22-24 are withdrawn. Claim 21 is objected to. Claims 1-5, 9-10, 15, and 26 are rejected. No claims are 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 ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642 /Laura B Goddard/Primary Examiner, Art Unit 1642
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