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 .
Restriction/Election
Applicant's election with traverse of the Requirement for Restriction/Election of Species (i.e., Species A: Seq ID Nos: 97, 54, 35, 1, 26, 3, 83 and 64, Species B: a drug, Species D: IL-P7-C05-H4L3) in the reply filed on 10 March 2026 (referred to herein as Remarks) is acknowledged (see Remarks pg. 12 Species A (bottom half of page). The traversal is on the ground(s) that the claims have been amended thus limiting the claim scope to antibodies to those with similar function and structure (see Remarks pg. 10, 1-3rd para). This is not found persuasive because the amended claims remain drawn to any immune cell (see claims 14 and 15); therefore, the claims remain drawn to distinct immune cells.
The requirement is still deemed proper for the reasons made of record and is therefore made FINAL.
However, in light of the elected species being free and clear of the prior art the species election of a particular anti-B7-H3 antibody (i.e., Species A), a particular structure conjugated to the antibody (i.e., Species B), and a particular active ingredient (i.e., Species D) are hereby withdrawn. It is noted the restriction between elected groups and Species C, E, F, and G is maintained.
Status of the Claims
Claims 1-10 were originally filed 12 December 2022. The preliminary amendments filed the same day, 6 October 2025, and 10 March 2026 have been entered.
Claims 11-14 and 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected Groups II-IV, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10 March 2026.
Claims 5-9 and 15 are currently pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Interpretation
Claim 5 is drawn to an antibody that comprises particular sets of HCDRs and LCDRs wherein “any one of the above amino acid sequences further includes a derivative sequence”. The language of claim 5 (similarly claim 6) is unclear (see USC112(b) rejections below). It is noted the claim recites “optionally with at least one amino acid added, deleted, modified, and/or substituted and can retain the binding affinity to B7-H3”. The claim language when read in light of this clause suggest the antibody can have at least one but up to all amino acids in the CDRs altered in some manner and bind any target as the claim prior to the “optionally” clause does not specify a target. It is unlikely Applicant intends to seek patent protection for any and all antibodies ever made. Therefore, for the purposes of prior art claims 5 and 6 are interpreted as requiring the claimed CDR sequences wherein there is/are additional “derivative sequences” present outside the claimed CDRs. It is also noted the specification claims humanized antibodies wherein there are limited and particular CDR substitutions in humanized frameworks (see specification examples starting on pg. 31).
Claim Objections
Claim 5 is objected to because of the following informalities:
Claim 5 recites, “(1) the heavy chain variable region” in line 2 and should recite “(1) a heavy chain variable region” for consistency. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Scope of Enablement
Claims 5-9 and 15 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 a B7-H3 antibody, does not reasonably provide enablement for an antibody that binds any target. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 Fed 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, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
Claim 5 is drawn to an antibody while the wherein clause specifies the antibody may retain binding to B7-H3. Therefore, the claim as a whole is intended to encompass an antibody that binds to more than one target.
The specification discloses the instantly claimed antibodies bind to B7-H3 (see specification pg. 2 lines 32-33, pg. 19 line 15-pg. 22 middle, pg. 33 Table 3, pg. 34 lines 1-18). The humanized anti-B7-H3 antibodies are in intended to be used to treat ailments with B7-H3 expression (see specification pg. 28 lines 8-31).
The state of the art is such that germline and affinity matured antibodies can have conformational flexibility which allows for the accommodation of different antigens (see Jaiswal et al. (2022) Antibody multispecificity: a necessary evil? Molecular Immunology 152, pgs. 153-161, pg. 155, 2nd col. 4th para). For example, the affinity matured anti-HER2 antibody, bH1, binds both HER-2 and VEGF and therapeutic antibody MEHD7945A binds both HER-3 and EGFR (see Jaiswal pg. 155, 2nd col. last para). In addition, degenerate antibodies have the ability to bind more than one target with no sequence similarity within the epitopes across targets as is the case with the G2 antibody known to bind different antigens (see Jaiswal gp. 156, 1st col. 2nd para). Jaiswal teaches that as few as 8 residues of about 30 may make direct contact with an antigen while the majority of the residues in the paratope contribute to a favorable architecture to antigen antibody interactions (see Jaiswal pg. 156, 2nd col). Thus, even affinity matured antibodies can interact with different antigens by engaging different residues within the CDRs (see Jaiswal pg. 156, 2nd col). In addition, degenerate antibodies that recognize more than one member of the chemokine family have been identified (see Angelini et al. (2018) Directed evolution of broadly cross-reactive chemokine-blocking antibodies efficacious in arthritis. Nat Commun 9, 1461, abstract). Specifically, Angelini teaches mutations in the CDRs and framework regions were critical for affinity toward ELR+ CXC chemokines (see pg. 5, 2nd col. last para, figure 3D). Degenerate chemokine ligand antibodies SA129 and SA138 were identifies as binding to 4 and 11 yeast displayed CXC chemokines (see Angelini pg. 6, 1st col. middle, figure 4a, b). Therefore, a person of ordinary skill in the art would recognize that a single set of CDRs may bind more than one target antigen with unrelated epitopes using different CDR residues and several degenerate antibodies targeting the ligands of the chemokine family have been identified.
Accordingly, in the absence of substantive direction or guidance in the instant specification, the entire scope of experimentation required to identify the breadth of targets (i.e., any target) that bind the instantly claimed CDRs comprising any framework region is left to those skilled in the art (i.e., trial and error). Given the resource intensive nature of the required experimentation, the skilled artisan would reasonably conclude that such experimentation would be unnecessarily, and improperly extensive and undue.
Written Description
Claims 5-9 and 15 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 5 is drawn to an antibody comprising 3 HCDRs and 3 LCDRs wherein any one of the claimed HCDRs or LCDRs further includes a derivative sequence. The specification does not provide a limiting definition for “derived”. It is noted the term is used various times throughout the specification such as the following:
“CD3ζ is a cytoplasmic signal transduction sequence derived from CD3ζ” (see specification pg. 10 line 25) and
“Humanized antibodies refer to antibody molecules derived from non-human species, with one or more complementarity determining regions (CDRs) derived from non-human species and framework regions derived from human immunoglobulin molecules” (see specification sentence spanning pgs. 18-19).
The broadest reasonable interpretation of a derivative when read in light of the specification and prior art is understood as any two amino acids with sequence identity to a starting sequence (see Merriam Webster definition: Derive, accessed online 05/19/2026).
David teaches that the mutations introduced in an antibody germline sequence as a result of somatic hyper mutation could cause derivatives to have altered affinity for its target (see David et al. A study of the structural correlates of affinity maturation: Antibody affinity as a function of chemical interactions, structural plasticity and stability. Molecular Immunology, 2007. 44:1342-1351, abstract). Furthermore, the sequence of the unmutated germline form of the antibody can only be guessed. Diversity at the V(D)J junctions, nucleotide additions and deletions during the rearrangement, and, in the case of heavy chains, the use of more than one D gene segment and the utilization of different reading frames result in amino acids that cannot be distinguished from those which result from somatic mutations (pg. 1343, 1st col. 2nd paragraph). The mutations that may occur at a given position, during somatic mutation, may be about 13-15 residues, given transitions are favored over transversions 2 to 1 (pg. 1349, 1st col.). David teaches that not all energetically favorable framework mutations introduced in an antibody germline sequence as a result of somatic hyper mutation were observed because these mutations would probably destabilize secondary structure or be incompatible, and disrupt some specific interactions such as disulfide bonds, salt bridges, hydrogen bonds, and other noncovalent interactions necessary for optimal protein function (see David pg. 1350, 1st col).
Applicant has disclosed anti-B7-H3 antibody ILP7C05 and 4 humanized variants (see specification pg. 33 Table 3). Among the humanized VH regions one has an alternative HCDR1 and 2 (i.e., ILP7C05huVH4) while a second has the same alternative HCDR2 (i.e., ILP7C05huVH3). In addition, among the humanized VL regions two have alternative HCDR2 regions (i.e., ILP7C05huVL2, ILP7C05huVL3). Across all CDRs there are no more than 6 substitutions across 58 positions. As an example the sequence alignment of the claimed VHs is below showing the parent antibody (i.e., Seq ID No: 79) has a high degree of sequence similarity to the humanized variants (i.e., Seq ID Nos: 80-83) (see sequence comparison below, bold text indicates positions with variability).
Claimed VH sequences (see instant claim 6)
US-17-928-423A-79 EVQLVESGGDLVQPGGSLKLSCAASGFTFSSYGMSWVRQTPDKRLELVAT
US-17-928-423A-82 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYGMSWVRQAPGKGLELVAA
US-17-928-423A-83 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLELVAA
US-17-928-423A-81 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYGMSWVRQAPGKGLELVAT
US-17-928-423A-80 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYGMSWVRQAPGKGLELVAT
US-17-928-423A-79 INSNGGTTYYPDSVKGRFTISRDNAKHTLYLQMSSLKSEDTAMYYCTRNE
US-17-928-423A-82 INSNGGSTYYADSVKGRFTISRDNAKNTLYLQMSSLRAEDTAVYYCTRNE
US-17-928-423A-83 INSNGGSTYYADSVKGRFTISRDNAKNTLYLQMSSLRAEDTAVYYCTRNE
US-17-928-423A-81 INSNGGTTYYADSVKGRFTISRDNAKNTLYLQMSSLRAEDTAVYYCTRNE
US-17-928-423A-80 INSNGGTTYYPDSVKGRFTISRDNAKHTLYLQMSSLRAEDTAVYYCTRNE
US-17-928-423A-79 EFRRGLAYWGQGTLVTVSA
US-17-928-423A-82 EFRRGLAYWGQGTLVTVSS
US-17-928-423A-83 EFRRGLAYWGQGTLVTVSS
US-17-928-423A-81 EFRRGLAYWGQGTLVTVSS
US-17-928-423A-80 EFRRGLAYWGQGTLVTVSS
Applicant has not disclosed antibodies comprising the claimed CDRs using alternative framework regions beyond minor substitutions in the parent antibody.
The specification does not disclose any correlation(s) between the structure of the derivatives the humanized anti-B7-H3 antibodies, or any correlations of structure and function. Furthermore, the specification does not disclose antibodies which bind to alternative epitopes (e.g., on B7-H3 or alternative target antigens) or a representative number of species that may bind the same epitope. The specification does not describe the structure, physical or chemical characteristics of derivative antibodies beyond a small subset that bind to the same target with similar affinities and highly overlapping sequence identities.
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 5-9 and 15 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.
Claim 5 is drawn to an antibody comprising particular Seq ID Nos. while also reciting these claimed Seq ID Nos. further comprise derivative sequences. The scope of the antibody is unclear. For example does the antibody require the recited sequences and an additional derivative sequence outside the CDRs, alternatively, does the antibody require the claimed sequences have additional alterations. In the case of the latter it is unclear how the claim can require both the recited Seq ID Nos. while also requiring those same sequences be altered. Likewise, claim 6 recites similar language. It is unclear how the antibody can comprise the recited sequences and an altered version of the sequence.
Claims 5 and 6 recite the limitation "the binding affinity to B7-H3" in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 is drawn to antibodies with particular pairs of VH and VL sequences. It is unclear if the table is drawn to reading horizontally (i.e., particular pairs of VH and VL sequences) or alternatively as independent columns. Examiner suggests amending the claim to remove the table and recite particular pairs of VH and VL sequences.
Claim 8 is drawn to a recombinant protein comprising: the antibody according to claim 5 and an optional tag sequence. The scope of the recombinant protein is unclear. For example is the recombinant protein drawn to comprising the antibody and any additional structure (i.e., encompasses a broad genus of structures), optionally a tag sequence. Alternatively, is the recombinant protein drawn to one of two embodiments either the antibody alone or the antibody and a tag sequence. Examiner suggests removing the “optional” from line three or alternatively removing line 3 altogether.
Claim 9 is drawn to a “coupling moiety” in part (b). it is unclear if the coupling moiety is selected from the group also recited in part (b) (i.e., wherein the coupling moiety is selected from the group consisting of). A “coupling moiety” is generally understood as a linker; therefore, the claim language “a coupling moiety coupled to” is unclear. For example, is this language interpreted as a linker coupled to an antibody moiety or alternatively is the linker (i.e., coupling moiety) what couples the antibody moiety to the moieties recited at the end of claim 9(b).
Claim 9 recites the limitation "the antibody moiety" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 15 is drawn to “an immune cell that expresses or is exposed outside the cell membrane the antibody”. In the embodiment where the active ingredient is an immune cell exposed outside the cell membrane with the antibody it is unclear if the antibody is required (i.e., bound).
Claim 15 recites the limitation "the cell membrane" in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
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 15 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 15 is drawn to an active ingredient that comprises an immune cell that is exposed outside the cell membrane with the antibody. Claim 15 depends from claim 5 which requires the antibody while claim 15 does not. Therefore, claim 15 broadens the scope of claim 5.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 5-9 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18/998199 (referred to herein as ‘199 application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The ‘199 application claims an antibody drug conjugate (see ‘199 claims 1-7 for linker drug limitations) comprising an anti-B7-H3 antibody (see ‘199 claim 8; see instant claims 5-9) and a pharmaceutical composition comprising the same (see ‘199 claim 9; see instant claim 15).
In performing the NSDP analysis, the first question to be asked is whether any examined claim is either anticipated by, or obvious over, a claim in the copending application. MPEP 804 (II)(B), second paragraph. While normally one cannot look into the specification of that copending application, it is in fact appropriate to learn which particular embodiments the claims cover. 804(II)(B)(1).
The ‘199 application discloses an anti-B7-H3 antibody comprising Seq ID Nos: 8 (VH) and 12 (VL) which are identical to the instantly elected VH and VL (see ‘199 application specification pg. 9 line 11-pg. 10 line 20; see instant Seq ID Nos: 83 and 64, respectively; see instant claim 6). Therefore the ‘199 application discloses and anti-B7-H3 antibody comprising the instantly elected/claimed HCDRs and LCDRs (see instant Seq ID Nos: 97, 54, 35, 1, 26, and 3; see instant claims 5 and 7).
Thus, when read in light of its corresponding specification, at least claims 1-9 anticipate present claims 5-9 and 15.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
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/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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