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 .
2. Applicant’s response filed on 04/16/2026 is acknowledged.
3. Claims 1-4, 8-9, 13-20, 22-24, 34, 36, 38-39, 41 and 46-56 are pending and under consideration for their full scope.
4. Applicant’s IDS documents filed on 08/12/2026 has been considered.
5. Claims 1-4, 8-9, 17-18, 20, 24, 38-39 and 41 are objected to because of the following informalities: claims 1-4, 8-9, 17-18, 20, 24 and 38-39 all refer to amino acid positions and do not indicate EU numbering. Claims 2 and 41 refer to EU numbering. The claims should indicate the numbering system and it should be used uniformly.
Appropriate correction is required.
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 1-4, 8-9, 13-20, 22-24, 34, 36, 38-39, 41 and 46-56 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 :
multispecific binding proteins comprising both heavy and light chains sequences wherein the second light chain does not comprise the recited mutations; and a method of production using a chromatography column using a kappa affinity ligand, does not reasonably provide enablement for : the multispecific binding protein and methods of production recited in claims 1-4, 8-9, 13-20, 22-24, 34, 36, 38-39, 41 and 46-56 for the same reasons as set forth in the Office Action mailed on 01/16/2026.
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 and use the invention commensurate in scope with these claims. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The claims only recite that first and second antigen binding domains comprise first and second light chain Fab regions. However, the binding proteins described in the description are heteromabs comprising a heavy chain and a light chain (In particular, examples). Antigen binding domains such as antibodies must have a pair of light and heavy chains to function, but the claims do not recite that the antigen binding domains comprise heavy chain Fab regions. One of ordinary skill in the art would not be able to make and use the invention commensurate in scope with the claimed invention. The specification discloses on pages 20-21 and in Table 3 that the presence of the recited mutations on only one of the light chains of the multispecific antibody appears to be an essential technical feature of the invention. The specification as filed shows that antibodies comprising the recited mutations on both light chains do not allow separation of the desired and undesired species. For example, the cMet parental mAb with DKK format for both light chain Fab regions abolishes binding to the Kappa XL column, thus 100% of the antibody was collected in the flow through and preventing differentiation of the desired and undesired antibody species. The specification discloses "Together, the results demonstrate that the kappa light chain Fab region formats of Table 1a, when expressed on only one light chain Fab region of an lgG heteromab, effectively differentiates the desired multispecific binding protein from the undesired species and thus enables for effective separation and purification of the desired binding protein".
As such, claims which are directed to antibodies wherein it is not specifically recited that the second light chain does not have the mutations that the first light chain does are not enabled. One of ordinary skill in the art would be required to perform undue experimentation to make and use the invention commensurate in scope with the claims.
Claim 24 and claims dependent thereupon recite the use of affinity chromatography to separate the desired species. The specification discloses on pages 20-21 and Table 3) the mutations of Kappa light chains and purification over a chromatography column comprising a kappa affinity ligand. As such, the claims are not enabled for use of any affinity chromatography columns to successfully separate the desired from the undesired binding protein species.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Applicant’s argument filed on 04/16/2026 have been fully considered, but are not found persuasive.
Applicant argues:
“The Office Action states that, although the specification is enabling for multispecific binding proteins comprising both heavy and light chains wherein the second light chain does not comprise the recited mutations, and for a method of production using a chromatography column with a kappa affinity ligand, the specification does not reasonably provide enablement for the full scope of the claims. Office Action at 3-4.
With respect to claim 24, an affinity chromatography to separate desired species is recited but not enabled for use of any affinity chromatography column to successfully separate the desired from the undesired binding protein species. In view of the present amendments, Applicant respectfully submits that this rejection is now moot.
It remains the Examiner’s position that the claims only recite that first and second antigen binding domains comprise first and second light chain Fab regions. However, the binding proteins described in the description are heteromabs comprising a heavy chain and a light chain (In particular, examples). Antigen binding domains such as antibodies must have a pair of light and heavy chains to function, but the claims do not recite that the antigen binding domains comprise the corresponding heavy chain Fab region sequences. One of ordinary skill in the art would not be able to make and use the invention commensurate in scope with the claimed invention. The specification discloses on pages 20-21 and in Table 3 that the presence of the recited mutations on only one of the light chains of the multispecific antibody appears to be an essential technical feature of the invention. The specification as filed shows that antibodies comprising the recited mutations on both light chains do not allow separation of the desired and undesired species. For example, the cMet parental mAb with DKK format for both light chain Fab regions abolishes binding to the Kappa XL column, thus 100% of the antibody was collected in the flow through and preventing differentiation of the desired and undesired antibody species. The specification discloses "Together, the results demonstrate that the kappa light chain Fab region formats of Table 1a, when expressed on only one light chain Fab region of an lgG heteromab, effectively differentiates the desired multispecific binding protein from the undesired species and thus enables for effective separation and purification of the desired binding protein".
Claim 24 and claims dependent thereupon recite the use of affinity chromatography to separate the desired species. The specification discloses on pages 20-21 and Table 3) the mutations of Kappa light chains and purification over a chromatography column comprising a kappa affinity ligand. As such, the claims are not enabled for use of any affinity chromatography columns to successfully separate the desired from the undesired binding protein species.
As such, claims which are directed to antibodies wherein it is not specifically recited that the second light chain does not have the mutations that the first light chain does are not enabled. Additionally the claims which do not recite the heavy chain Fab regions to be paired with the recited light chain Fab regions are not enabled. One of ordinary skill in the art would be required to perform undue experimentation to make and use the invention commensurate in scope with the claims.
Applicant’s amendments have not overcome the instant rejection. The rejection stands for reasons of record.
8. No claim is allowed.
9. 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 extension fee 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 date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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September 17, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
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