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 .
Applicant’s response filed on 11/18/2025 is acknowledged.
Claims 1-26, 28, 30, 34, 36, 38-39, 41-43 and 46-56 are pending.
Upon reconsideration, the restriction requirement mailed on 09/18/2025 is withdrawn.
Claims 1-26, 28, 30, 34, 36, 38-39, 41-43 and 46-56 are under consideration for their full scope.
6. Applicant’s IDS documents filed on 09/02/2022, 10/17/2022, 05/06/2024 and 01/08/2026 have been considered.
7. 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.
8. Claim 14 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 14 recites the limitation "the first heavy chain Fc region" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is suggested that Applicant amend the claims to recite that dependency upon claim 13 instead.
Correction is required.
9. 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.
10. Claims 1-26, 28, 30, 34, 36, 38-39, 41-43 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 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 1-26, 28, 30, 34, 36, 38-39, 41-43 and 46-56.
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.
11. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
12. 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.
13. Claims 1-2, 8-9, 11-13, 15 and 21-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Australian public assessment report for Catumaxomab (IDS filed on 01/08/2026; Reference 8) as evidenced by P20766 (IDS filed on 01/08/2026; reference 9) and WO 2017/005649 (IDS filed on 01/08/2026; Reference )
Australian public assessment report for Catumaxomab teaches that Removab (catumaxomab), a therapeutic antibody for malignant ascites, comprises mouse kappa light (corresponding to the presently claimed "first light chain Fab region") and IgG2a heavy chains and rat lambda light (corresponding to the presently claimed "second light chain Fab region") and IgG2b heavy chains ("Product background" and Figure 1).
As evidenced by WO 2017/005649, mouse Ig kappa chain comprises 109A, 110D 143V and 199K. (In particular, Figure 1).
As evidenced by P20766, the rat Ig lambda chain comprises 109P, 110K and 199E.
The reference teachings anticipate the claimed invention.
14. 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.
15. Claims 24, 28, 30, 34, 36, 42-43 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Australian public assessment report for Catumaxomab (IDS filed on 01/08/2026; Reference 8) in view of JPH09-506001A (IDS filed on 01/08/2026; Reference 1) as evidenced by the translation in WO95/33844 (IDS filed on 01/08/2026)
Australian public assessment report for Catumaxomab teaches that Removab (catumaxomab) is produced by a quadroma cell line ("Product background"), but does not describe its specific purification method.
The claimed invention differs from the prior art in the recitation of the method of producing the multispecific binding protein of claims 24, 28, 30, 34, 36, 42-43 and 46.
JPH09-506001A teaches a method for making heterologous bi-specific antibodies
(bsAbs) comprising the steps of: (a) providing a quadroma fused from hybridomas of which one produces first antibodies which have an affinity to the binding domain of protein A wherein said first antibodies are mouse antibodies, humanized antibodies, or the like and the other hybridoma produces second antibodies which, in comparison with the first antibodies, have a smaller or no
affinity to the binding domain of protein A, the second antibodies being rat antibodies of the subclass IgG2b or humanized antibodies; (b) multiplying and cultivating the quadromas in the usual manner; (c) applying the quadroma culture supernatant to a column which is coated with a material which contains binding domains of protein A as functional groups (corresponding to
the presently claimed "affinity chromatography column"); (d) washing out in the respective pH range the proteins which are not bonded; and (e) subjecting the bsAbs to elution in a pH range which is at least 0.5 units above the pH at which the antibodies with greater affinity to the binding domain of protein A are still bonded (claim 1); that the heterologous bsAb comprises a mouse antibody of the subclass IgG2a fused with a rat antibody of the subclass IgG2b (claim 3);
that the method claimed therein can produce high purity heterologous bsAbs; that an important point of this new purification principle for bsAbs is that one of the parental antibodies, which are secreted from the quadroma cells, does not form a bond with protein A; and that one of the hybridoma cell lines, which is fused with a second hybridoma cell line to form a quadroma, produces an antibody which does not form a bond with protein A (WO95/33844, description, page 4, fifth paragraph from the bottom; page 5, first paragraph from the bottom).
It would have been obvious to have combined the teachings of the references because both references relate to a heterologous bispecific antibody comprising a mouse antibody and a rat antibody. Those skilled in the art would have used the method of JPH09-506001 to produce high purity heterologous bispecific antibodies by applying the quadroma culture supernatant to a column which is coated with a material which contains binding domains of protein A as functional groups for higher purification of the antibodies, as described in D2. In addition, the purification could have been repeated a desired number of times, if necessary, by those
skilled in the art.
From the combined teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
16. No claim is allowed.
17. 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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January 10, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641