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 .
Status of the Claims
Claims 1-10 were originally filed 3 May 2021. The preliminary amendment filed 3 May 2021 has been entered. Claims 1, 4, 6-9, and 17 are currently pending and under consideration.
Claim Interpretation
Claim 8 is drawn to a preparation method of the bispecific antibody comprising “constructing an expression vector” (see line 2). Therefore, claim 8 is interpreted as comprising a single expression vector encoding both the single chain antibody and the monoclonal antibody comprising the heavy chain and light chain.
Withdrawn Rejections
In view of Applicant amending claim 1 to remove “unit”, the multiple references to various structures using (a), (b), (i), and (ii), and clarify the linker comprises Seq ID No: 13, the 35 USC 112(b) rejection of claim 1 regarding these matters are hereby withdrawn.
In view of Applicant amending claim 6 to clarify the DNA fragments encode the bispecific antibody the 35 USC 112(b) and 35 USC 112(d) rejections over claim 6 are hereby withdrawn.
In view of Applicant amending claim 17 the 35 USC 112(d) rejection of claim 17 is hereby withdrawn.
In view of Applicant amending claim 1 to recite, “wherein each of the two single-chain antibodies is a fusion peptide having an amino acid sequence set forth in Seq ID No: 18” in lines 15-16 all prior art rejections under 35 USC 103 are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 4, 6-9, 17, 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.
The claim recites, “the bispecific antibody has a symmetric structure formed by a linkage in one of the following modes (1) and (2)” (lines 7-8) and further recites 2 CD3 scFvs are connected via the N-terminal ends of the monoclonal HCs and 2 CD3 scFvs are connected via the C-terminal ends of the monoclonal HCs ultimately requiring 4 CD3 scFvs. It is unclear how many CD3 scFvs are required in the bispecific structure. For example, is the claim drawn to a symmetric structure formed by a linkage in one of two modes (i.e., one of the following modes: (1) or (2)) or alternatively does the claim require 4 CD3 scFvs as the claim also suggests with the recitation of “and” between modes (1) and (2) (see lines 8 and 11).
The following rejections are necessitated by amendment.
Claim Rejections - 35 USC § 112(b)
Claims 1, 4, 6-9, and 17 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.
The scope of the fusion peptide is unclear. Claim 1 is drawn to two single-chain antibodies that specifically bind to CD3 in line 7 while also reciting, “wherein each of the two single-chain antibodies is a fusion peptide having an amino acid sequence set forth in Seq ID No: 18” in lines 15-16. The specification discloses Seq ID NO: 18 is the light chain variable region of the monoclonal antibody which binds to CD19 (see specification pg. 5 line 21, pg. 7, 1st full para). Therefore, it is unclear how the fusion peptide that specifically binds CD3 can comprise a light chain variable region that specifically binds CD19.
Claim Rejections - 35 USC § 112(d)
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 8 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 8 is drawn to “an expression vector containing a DNA fragment of said two single-chain antibodies and the monoclonal antibody component” in lines 3-4. Claim 1 is drawn to a bispecific antibody comprising two heavy and light chain pairs (i.e., monoclonal antibody component) and at least 2 scFv structures. Therefore, claim 8 expands the scope of claim 8 by allowing fragments of the bispecific antibody of claim 1.
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.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1, 4, 6-9, and 17 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is drawn to a bispecific antibody that comprises two CD3 single chain antibodies each comprising Seq ID No: 18.
The specification discloses Seq ID No: 18 is the light chain variable region of a CD19 monoclonal antibody (see specification pg. 5 line 21, pg. 7, 1st full para, pg. 14, 6th para). There is no evidence from the disclosure that CD3 scFvs comprising Seq ID No: 18 alone or paired with any heavy chain variable region were made or used.
The state of the art teaches CDR sequences are the residues required for antigen binding and these sequences are highly variable in order to facilitate binding to a multitude of antigens (see Kapingidza et al. 2020. Antigen-Antibody Complexes. Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid, CH 19, pgs. 465-484, pg. 468, lines 1-4; see Culang et al. The structural basis of antibody-antigen recognition. Front. In Immun. 2013. Vol. 4, Article 302, abstract). The state of the art also teaches the mutation effects at interfaces are often unpredictable and more often than not result in decreased binding affinity (see Clark et al. Influence of canonical structure determining residues on antibody affinity and stability. Journal of Structural Biology 185 (2014) 223–227, pg. 223, 2nd col. 1st full para).
Accordingly, in the absence of substantive direction or guidance in the instant specification, the scope of experimentation required to develop antibodies with any HCDRs 1-3 paired with instant Seq ID No: 18 that results in an antibody that binds to CD3 is left to those skilled in the art. Given the unpredictability in altering a single amino acid or combinations thereof, the present claims and disclosure amount to an invitation to the skilled artisan to develop such embodiments. Therefore, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly, extensive and undue.
Claims 1, 4, 6-9, and 17 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 1 is drawn to a bispecific antibody that comprises two CD3 single chain antibodies each comprising Seq ID No: 18.
The specification discloses Seq ID No: 18 is the light chain variable region of a CD19 monoclonal antibody (see specification pg. 5 line 21, pg. 7, 1st full para, pg. 14, 6th para). There is no evidence from the disclosure that CD3 scFvs comprising Seq ID No: 18 were made or used.
The state of the art teaches CDR sequences are the residues required for antigen binding and these sequences are highly variable in order to facilitate binding to a multitude of antigens (see Kapingidza et al. 2020. Antigen-Antibody Complexes. Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid, CH 19, pgs. 465-484, pg. 468, lines 1-4; see Culang et al. The structural basis of antibody-antigen recognition. Front. In Immun. 2013. Vol. 4, Article 302, abstract).
Therefore, a person of ordinary skill in the art at the time of filing would understand residues within the CDRs are integral to antigen recognition. As there is no art recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which heavy chain complementarity determining regions paired with Seq ID NO: 18 and result in an antibody that binds to CD3. Overall based on the disclosure, the state of the art at the time of filing, a skilled artesian would have to recognize that Applicant was not in possession of the claimed invention at the time of filing.
Conclusion
No claim 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.
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/H.A.P./Examiner, Art Unit 1644 /AMY E JUEDES/Primary Examiner, Art Unit 1644
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