DETAILED ACTION
1. 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 election of Group I (drawn to a trispecific antibody) and the species NKG2D as second target and CD19 as third antigen target having SEQ ID NOs: 225-227 in the reply filed on July 15, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 2, 6-9, 11, 14-22, 24-27, 29-31, 34, 35, 42, 43, 47, and 48 have been canceled.
Claims 1, 3-5, 10, 12, 13, 23, 28, 32, 33, 36-41, and 44-46 are pending.
Claims 37-40, 44, and 46 have been withdrawn under 37 CFR 1.142(b) as being drawn to nonelected inventions.
Claims 1, 3-5, 10, 12, 13, 23, 28, 32, 33, 36, 41, and 45 are currently under consideration as they read on the elected invention.
3. 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.
4. Claims 3, 5, and 33 are 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.
A) claim 3 is indefinite in the recitation of wherein the A and B binding domains are “positioned to each other in a way that simultaneous binding to two immune effector cells is reduced or prevented” because the metes and bounds of the phrase is unclear. It is not clear how A and B binding domains are positioned for the function of reducing or preventing simultaneous bindings. In addition, the term “reduced” in the claim is a relative term which renders the claim indefinite. The term “reduced” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
B) claim 5 is indefinite in the recitation of “preferably”, e.g. preferably comprises a CH2 domain, wherein the Fcγ receptor binding domain is silenced, because the metes and bounds of the claim is ambiguous. It is not clear whether the claimed preference is a limitation of the claim. The recitation of the preferences leads to confusion over the intended scope of the claims.
C) claim 33 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush grouping of the antibodies with different amino acid sequence is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Each of the antibodies has unique antigen binding domain including CDRs or VH/VL sequences which are not shared by other antibodies with CDRs or VH/VL. The elected antibody having amino acid sequences set forth in claim 33 encompassing SEQ ID NOs: 225-227 does not share the CDRs or VH/VL with the other antibodies
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
5. 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.
6. Claim 45 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.
Claim 45 recites a kit comprising the antibody construct of claim 1, a nucleic acid molecule….. a vector…. And/or a host cell…..”.
Claim 1 encompasses only a trispecific antibody construct, not nucleic acid, vector, and/or host cell.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
7. 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.
8. Claims 32 and 33 are 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.
Claim 32 is drawn to an antibody construct of claim 1 wherein the first binding domains comprises
(i) A VL region comprising three CDRs L1-L3 selected from
(a) CDR-L1-L3 of SEQ ID NOs: 29, 30, and 31, and
(b) CDR-L1-L3 of SEQ ID NOs: 35, 36, and 37,
(ii) a VH comprising CDR-H1-3 selected from
(a) CDR-H1-3 of SEQ ID NOs: 26, 27, and 28, and
(b) CDR-L1-3 of SEQ ID NOs: 29, 30, and 31.
Claim 33 is drawn to an antibody construct of claim 1 having an amino acid sequence selected from the group consisting of 225-227 (the elected species).
There is insufficient written description in the specification as-filed of the antibody as recited in instant claims 32 and 33.
Applicant has claimed an antibody that have two VLs or mix match VL in claim 32(s) with the VH in claim 32(ii) as well as an antibody having one amino acid sequence in claim 33.
The specification discloses antibody (e.g. anti-CD16 antibody for first binding domain A) having six CDRs or VH and VL (e.g. see Table 12 in page 108 of the specification as-filed).
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. 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 parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection). Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
Goel et al. (The Journal of Immunology, 2004, 173:7358-7367) disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document).
As such, it does not seem possible to combine VH and VL from different antibody clones to give rise to the function of antigen binding (e.g. CD16 binding by mix and match VH and VL from different clones).
Further, it is unlikely that the antibodies as defined by the instant claim 33, which contain only one amino acid sequences and not all CDRs (e.g. an amino acid sequences selected from the group consisting of SEQ ID NOs: 225-227) would have the required function for antigen binding.
It is noted that the specification does disclose a working example of specific antibodies that binds CD16, NKG2D, and CD19 antigen in the trispecific antibody format.
However, these antibody species having specific amino acid sequences for the VH and VL domains are not reasonably representative of the species of currently recited including mix and match VH and VL for CD16 binding or single chain antibody encompassed by claim 33.
Therefore, in view of the breadth of the claims, artisans would reasonably conclude that applicant was not in possession of the full breadth of the antibody recited in instant claims 32 and 33 at the time the instant application was filed.
9. 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.
10. 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.
11. Claims 1, 3, 4, 5, 10, 12, 23, 36, and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ellwanger et al. (US 2019/0040155).
Ellwanger et al. teach a multispecific antibody that contains three antigen binding domains, each comprising VH and VL, that can bind three antigens, wherein the antigen binding domains are fused to each other as diabody (e.g. see Figure 1).
Ellwanger et al. further teach the multispecific antibody is a trispecific antibody have two specificities for different antigens on the effector cells such as NK-cells and a third specificity for an antigen on a tumor cell (e.g. see [0068]). Ellwanger et al. teach the two antigens on effector cells can be CD16 and NKG2D (e.g. see [0069]) and the tumor specific antigen can be CD19 (e.g. see [0078]). Ellwanger et al. teach that the multispecific antibody can comprise an Fc domain which is known to extend serum half life of a protein (e.g. see [0046]). Ellwanger et al. teach a pharmaceutical composition comprising the multispecific antibody (e.g. see [0090]). Given that the prior art multispecific antibody comprises antigen binding sites for NK cells and tumor antigen, it would be expected to bind a target cell expressing the tumor antigen CD19 and immune effector NK cells simultaneously.
Further, given that the antigen binding domains to CD16 and NKG2D on NK cells would be linked as diabody as the instantly disclosed trispecific antibody, the simultaneous binding to CD16 and NKG2D on two different NK cells for the prior art multispecific antibody would be reduced without evidence to the contrary.
Therefore, the reference teachings anticipate the instant invention.
12. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
13. Claims 1 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Ellwanger et al. (US 2019/0040155) in view of Hardman et al (US 5,843,708).
The teachings of Ellwanger et al. have been discussed, above.
The reference teachings differ from the instant invention by not describe a kit.
The instant claims recite a kit, however, no positive recitation of the ingredients distinguishes it over the reference. It is a well-known convention in the art to place these components in a pack for convenience and economy. For example, Hardman et al. teach a kit, comprising antibodies and buffer solutions and detergents for preventing non-specific adsorption and aggregate formation, for immunoassays and immunotherapies (e.g. see columns 18 and 19).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include the necessary reagents to perform the immunoassays or immunotherapies in a kit format for the convenience and economy of the user. One would have been motivated to assemble the reagents in a kit format to standardize the reagents for the optimization the assay for use in a clinical diagnostic laboratory or physician's office. 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 references, especially in the absence of evidence to the contrary.
14. A trispecific antibody construct comprising an anti-CD16 antibody, an anti-NKG2d antibody and an anti-CD19 antibody wherein the trispecific antibody comprises SEQ ID NOs: 225-227 is free of the prior art.
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 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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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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