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 . 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.
Election/Restrictions
Applicants elected group I (conjugates) and the species of 225Ac labeled trastuzumab of example 1 with traverse in the reply filed on 31 Dec, 2025. The traversal was found unpersuasive and the election/restriction requirement made final in the office action of 20 Feb, 2026.
Claims Status
Claims 1, 4-12, 15, and 16 are pending
Claims 1 and 9 have been amended.
Claims 15 and 16 are new.
Claims 10-12 and 16 have been withdrawn due to an election/restriction requirement. Note that example 1 uses an acetate buffer, as opposed to the buffers of claim 16.
Withdrawn Rejections
The rejection of claim 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph due to a range of timescales at which a measurement could be taken is hereby withdrawn due to amendment.
The rejection of claims 13 and 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph due to lack of details of storage under which the conjugate is subjected to for the test is hereby withdrawn due to amendment.
The rejection of claim(s) 1, 3, 4, 6, 8, 9, and 14 under 35 U.S.C. 102(a)(1 and 2) as being anticipated by Ito et al (WO 2017217347) is hereby withdrawn due to amendment.
The rejection of claim(s) 13 and 14 under 35 U.S.C. 102(a)(1 and 2) as being anticipated by Dudkin et al (WO 2019125982) is hereby withdrawn due to amendment.
Maintained/Modified 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 and 4-9 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 1, and claims dependent on it, require that the linker not contain a thiourea bond. However, the end of the linker and the beginning of the antibody or chelating agent is arbitrary. For example, applicants have a dependent claim describing the chelating agent as DOTAGA-DBCO. However, there are 6 carbons and 2 nitrogens in the chain between the cyclooctyne unit and the DOTA which does the conjugation. If a derivative where the cyclooctyne was connected to the DOTA via a thiourea linkage, it will not be clear if the thiourea is part of the linker or part of the chelator – the distinction is only in the mind of the person making the conjugate. Note that the same argument can be made for the linker as well – its presence or absence is dependent on where the cutoff is between the antibody, linker, and chelator is, and those cutoffs exist only in the mind of the person designing the conjugate.
response to applicant’s arguments
Applicants state that they have amended around this limitation.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
While applicants have added more details, they have not overcome the basis of the rejection, that some components cannot have a thiourea linkage have cutoff points that are defined only in the head of the person designing the conjugate.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
first rejection
Claim(s) 1 and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Dudkin et al (WO 2019125982, cited by applicants) in view of Ito et al (WO 2017217347, cited by applicants), with evidentiary support from Maguire et al (J. Nuc. Med. (2014) 55 p1492-1498). Ito et al is in Japanese, so Ito et al (US 20200181196, cited by applicants), the national stage application of the WIPO document, is used as a translation. All locations referred to in the rejection are for the US version of the document.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
The difference between this reference and the examined claims is that this reference does not conjugate to a peptide site specifically labeled to the antibody via a peptide.
Ito et al discuss using IGG binding peptides for site specific radiolabeling of antibodies (title). Non-site specific labeling can reduce the activity of the antibody, and make it difficult to control the amount of radiation bound (paragraph 3). A preferred peptide is SEQ ID 2, GPDCAYH(Xaa)GELVWCTFH (paragraph 68), with Xaa1 being a lysine residue and the two Cys residues forming a disulfide bond a particularly preferred species (paragraph 69). Note that this is the same peptide used in applicant’s elected species. This peptide can be covalently attached to the antibody using a disuccinimidyl glutarate (DSG) to a lysine residue (paragraph 85), the same linker at the same location as used in applicant’s elected species. The other side of the crosslinker preferably binds to Lys248 of IgG Fc domain (paragraph 90)(i.e. site specific). An example of this peptide with a tetra-PEG sequence attached to the N-terminus, DSG attached to the lysine was and linked to DTPA (paragraph 153) and bound to Trastuzumab, and anti-Her2 antibody (paragraph 154), and labeled with 111In (paragraph 155). This reference discusses using a site specific binding peptide to radiolabel antibodies.
Therefore, it would be obvious to use the site specific binding peptide of Ito et al in radiolabeling an antibody with the methods of Dudkin et al, for better control of labeling and to avoid reducing the antibody activity, as mentioned by Ito et al. As both references discuss radiolabeling of antibodies using similar chelators, an artisan in this field would attempt this modification with a reasonable expectation of success.
The combination has an anti-Her2 antibody modified with a chelator and a site specific binding peptide, where neither reference mentions thioisocyanate, thiourea, or chemistry that leads to a thiourea. Ito et al describes a peptide used as a linker that meets the limitations of examined claim 1. Dudkin et al teaches DOTA-GA-DBCO, rendering obvious claims 1, 5, and 7.
Dudkin et al teaches 225Ac, rendering obvious claim 4.
Both references discuss a PEG linker, rendering obvious claim 6.
Both references use Trastuzumab, rendering obvious claim 8.
Claim 9 describes an intended use. There is nothing in the conjugate of the rejection that makes it unsuitable for this intended use, rendering the claim obvious.
response to applicant’s arguments
Applicants argue that none of the references disclose that the conjugate is more stable than one using a thiourea linkage.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation and is not a requirement for a valid rejection.
second rejection
Claim(s) 1, 4-9, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Dudkin et al (WO 2019125982, cited by applicants) in view of Ito et al (WO 2017217347, cited by applicants), and Lovhaug et al (US 20090208412), with evidentiary support from Maguire et al (J. Nuc. Med. (2014) 55 p1492-1498).
The teachings of Dudkin et al, Ito et al, and Maguire et al were given above, and will not be repeated here. Note that these references render obvious claims 1 and 4-9.
The difference between these references and applicant’s elected species is that they use a slightly different linker between the peptide and the chelator.
Lovhaug et al discuss contrast agents for detecting collagen (abstract). These comprise a collagen binding moiety connected to a detection moiety optionally through a linker (paragraph 24). The reporter moiety can be a radioisotope (paragraphs 32 and 33), which, if appropriate, will have a chelating agent (paragraph 34), such as DOTA (paragraph 45). A preferred embodiment uses a linker
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with m=1-10 (paragraph 60). Note that this is identical with the linker of applicant’s elected species, save that number of PEG units is 3 rather than 8. However, Lovhaug et al also mentions the PEG linker being between 1 and 10 units (paragraph 60), a genus that includes the 8 PEG units used by applicants.
Therefore, it would be obvious to use the linker of Lovhaug et al, as a substitution of one known element (the PEG linkers of Dudkin et al and Ito et al) for another (the modified PEG linker of Lovhaug et al) yielding expected results (the chelator attached to the peptide). As Lovhaug et al is also discussing radiolabeling a peptide with a chelate attached by a linker, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants argue that there is no motivation to avoid a thiourea linkage, and that none of the references disclose that the construct is more stable than a hypothetical construct with a thiourea linkage.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants argue that there is no disclosed motivation to avoid a thiourea linkage. However, the primary reference discloses DOTA-GA-DBCO reacting with an azide to form a triazole linkage, not an isothiocyanate to form a thiourea linkage. It is not clear why a reason to remove a thiourea linkage is necessary when there is no thiourea linkage to remove.
Applicants further argue that none of the cited references disclose that the linker is more stable than a hypothetical linker with a thiourea connection. However, that is not a claim limitation.
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.
first rejection
Claims 1, 4-9, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 14, and 15 of copending Application No. 18/556,527 (US 20240207464) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claims 1-8, 10, 14, and 15 are almost identical to the corresponding examined claims, save they are directed to an antibody that binds to a different target.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the antibody of the competing claims is a teaching away from using a different antibody due to loss of specificity of the antibody.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicant’s argument is essentially pointing to a difference and saying it is a teaching away. However, it is not clear that binding to CD20 is the only feature required of any antibody, so it is not clear why this is a teaching away.
second rejection
Claims 1, 4-9, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9, 13, and 14 of copending Application No. 18/553,443 (US 20240207463) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claims 1-8, 10, 14, and 15 are almost identical to the corresponding examined claims, save they are directed to an antibody that binds to a different target.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the antibody of the competing claims is a teaching away from using a different antibody due to loss of specificity of the antibody.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicant’s argument is essentially pointing to a difference and saying it is a teaching away. However, it is not clear that binding to EGFR is the only feature required of any antibody, so it is not clear why this is a teaching away.
third rejection
Claims 1, 4, 5, and 7-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 8, 11, and 16 of copending Application No. 18/668,001 (US 20240207464) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claim 1 specifies a chelating agent, a radionucleotide, and an antibody connected via a linker. Competing claim 2 specifies the same peptide as examined claim 3, while competing claim 4 specifies the same peptide as applicant’s elected species. Competing claim 8 specifies that the radionucleotide is 225Ac, while competing claim 11 is identical to examined claim 9. Competing claim 16 specifies that the chelator is DOTA-GA-DBCO.
The difference between the competing claims and the examined claims is that the competing claims do not specify the antibody.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the competing claims do not disclose that the conjugate is more stable than one using a thiourea linkage.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation.
fourth rejection
Claims 1, 4-9 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11, 20, and 25 of copending Application No. 17/769,657 (US 20230248854) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claim 1 describes an antibody-radioactive metal complex connected via a peptide, and describing the chelating group. Competing claim 20 specifies that the antibody be Trastuzumab of Rituximab. Competing claim 25 specifies the same chelator-linker as applicant elected species.
The difference between the competing claims and the examined claims is that the competing claims do not discuss 225Ac.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the 225Ac of Dudkin et al for the unspecified radioisotope of the competing claims, as a substitution of one element (the unspecified radionucleotide of the competing claims) for another (the radionucleotide of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the competing claims do not disclose that the conjugate is more stable than one using a thiourea linkage.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation.
fifth rejection
Claims 1, 4-9, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-10, of copending Application No. 18/838,934 (US 20250152760) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claims 1-3 and 5-10 are almost identical to the corresponding examined claims, save they are directed to an antibody that binds to a different target.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the competing claims do not disclose that the conjugate is more stable than one using a thiourea linkage.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation.
fifth rejection
Claims 1, 4-9, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5-10, of copending Application No. 18/838,934 (US 20250152760) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claims 1-3 and 5-10 are almost identical to the corresponding examined claims, save they are directed to an antibody that binds to a different target.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the antibody of the competing claims is a teaching away from using a different antibody due to loss of specificity of the antibody.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicant’s argument is essentially pointing to a difference and saying it is a teaching away. However, it is not clear that binding to VEGF is the only feature required of any antibody, so it is not clear why this is a teaching away.
sixth rejection
Claims 1, 4-9, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 9, and 10, of copending Application No. 17/367,077 (US 20210338852) in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claim 1 describes an antibody chelated to Zr-89, connected by a peptide and a DOTA chelator. Competing claim 5 specifies a Markush group of peptides, including applicant’s elected peptide sequence. Competing claim 8 specifies DOTA-GA, and competing claim 10 specifies a Markush group of cyclooctyne based click chemistry reagents.
The difference between the competing claims and the examined claims is that the competing claims do not put together the chelator and the DBCO, use a different radionucleotide than some claims, and use a different antibody.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab of Dudkin et al for the antibody of the competing claims, as a substitution of one element (the antibody of the competing claims) for another (the antibody of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
Furthermore, it would be obvious to use the radionucleotide and linker/chelator of Dudkin et al, for the same reason, with the same reason for a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the competing claims do not disclose that the conjugate is more stable than one using a thiourea linkage, and that changing the antibody of the competing claims is a teaching away.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation.
Applicant’s second argument is essentially pointing to a difference and saying it is a teaching away. However, it is not clear that binding to MUC5AC is the only feature required of any antibody, so it is not clear why this is a teaching away.
seventh rejection
Claims 1, 4-9, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,701,440 in view of Dudkin et al (WO 2019125982, cited by applicants).
Competing claims 1 describes an antibody conjugated to a radionucleotide via a peptide and a chelator comprising DOTA. Competing claim 2 specifies a DBCO group, while competing claim 3 specifies a PEG linker. Competing claim 4 specifies applicant’s elected peptide species.
The difference between the competing claims and the examined claims is that the competing claims do not specify the antibody or the radionucleotide, and use a slightly different chelator.
Dudkin et al discuss raidolabeling of antibodies (abstract). Radioisotopes that can be used include 225Ac, applicant’s elected radioisotope (p9, 1st paragraph), and the chelator can be attached to the antibody using click chemistry with DOTA-DBCO (p9, 2nd paragraph). A preferred embodiment using a chelating moiety of formula (II)
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(18, 2nd paragraph). Note that this is identical to the chelating agent of claim 7. An example is given of conjugating NHS-PEG4-azide to Trastuzumab (p42, 3d and 4th paragraphs). Actinium 225 was reacted with DOTA-GA-DBCO (p46, 2nd paragraph) and conjugated to the antibodies using click chemistry (p47, 4th paragraph, continues to p48, 2nd paragraph). Note that Trastuzumab was used in this reaction (table 3, p52, continues to p53).
Therefore, it would be obvious to use the Trastuzumab and 225Ac/chelator of Dudkin et al for the antibody and radionucleotide/chelator of the competing claims, as a substitution of one element (the antibody and radionucleotide of the competing claims) for another (the antibody and radionucleotide of Dudkin et al) yielding expected results (labeled antibody). As Dudkin et al discusses similar chelators for a similar purpose, an artisan in this field would attempt this substitution with a reasonable expectation of success.
response to applicant’s arguments
Applicants argue that the competing claims do not disclose that the conjugate is more stable than one using a thiourea linkage, and that the rationale of the competing claims is different, a teaching away.
Applicant's arguments filed 3 June, 2026 have been fully considered but they are not persuasive.
Applicants are arguing that the prior art does not disclose that the linker is more stable than some poorly defined hypothetical linker. However, that is not a claim limitation.
Applicants argue that the rationale for the linker of the competing claims is different than that of the examined claims, a teaching away. It is not clear why this is a teaching away. A rationale different than applicants is not sufficient to make a rejection invalid (MPEP 2144).
Conclusion
THIS ACTION IS MADE FINAL. 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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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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