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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 6/9/2026 wherein claims 1-10 and 15-29 were canceled and claims 32 and 33 were amended. In addition, the Examiner acknowledges the amendment filed 1/26/2026 wherein the specification was amended.
Note(s): Claims 11-14 and 30-37 are pending.
Priority
This application claims benefit to PRO 63/181,126 filed 4/28/2021.
Note(s): The earliest effective filing date is 4/28/2021 as the pending invention is fully supported by the provisional application.
Claim Interpretation
Amended independent claim 11 is directed to a conjugate comprising a bis-B10 compound having a first closo-decaborate moiety and a second closo-decaborate moiety wherein
the first closo-decaborate moiety is covalently linked to a trivalent group by a first linker group,
the second closo-decaborate moiety is covalently liked to the trivalent group by a second linker group,
the trivalent group is covalently linked to a targeting agent, and
the first closo-decaborate moiety and the second closo-decaborate moiety are linked by an astatine atom or an astatine oxide group.
Claim 30 is directed to a method for introducing an astatine isotope into a subject, comprising administering a conjugate of claim 11 to a subject in need thereof.
Claim 31 is directed to a method for treating a disease or condition treatable by the administration of an astatine isotope, comprising administering a therapeutically effective amount of a conjugate of claim 11 to a subject in need thereof.
Applicant’s Election
Once again, Applicant’s election of Group III (pending claims 11-14 and 32-37) in the reply filed on 7/9/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election was treated as an election without traverse (MPEP § 818.01(a)). Thus, the restriction was deemed proper and made FINAL.
Once again, Applicant elected the species of Figure 25 for initial examination. In the response filed 7/9/2025, Applicant indicated that one elected Compound 16. However, it appeared to be an inadvertent error as the elected Group III (see independent claim 11) must contain astatine (At). Thus, since Compound 16 and Compounds 17A and 17B differ by the presence of X = At or AtO, it appears to be an inadvertent error in listing Compound 16 instead of Compounds 17A or 17B.
For the elected species Applicant indicated that the various M, Z, L, Y, L1, L2, Ar1, and Ar2 are defined as follows (see the claims from 7/9/2025): M = monoclonal antibody; Z = thiourea functionality; L = not present in this structure; Y = 5-aminoisophthalic acid (amine is part of thiourea functionality); L1 and L2 both are -NHCH2CH2OCH2CH2OCH2CH2NH-CO-NH-; Ar1 and Ar2 are both B10H92-.
In independent claim 11, L is required, not optional. Thus, the elected species does not read on independent claim 11 unless the variable L is present. Nonetheless, Compounds 17A and 17B were examined and no prior art found to reject the claims.
Clarification of the Record
It is duly noted that Applicant has once again submitted the claims for which a non-response communication was mailed. Thus, in an effort to advance prosecution the claims have been evaluated as set forth in detail below.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 6/9/2026 to the rejection of claims 11-14, 18, 20-24, and 26 made by the Examiner under 35 USC 112 (first and second paragraphs) and improper Markush have been fully considered and deemed persuasive-in-part for the reasons set forth below.
Written Description Rejection
Note(s): It is duly noted that Applicant amended the claims to address the 112 first paragraph (written description) rejection. The written description rejection below is modified to address the pending claims.
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 11-14 and 32-37 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to species encompassed by the limitations present in independent claim 1 except Compounds 17a and 17b. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the conjugates of claim 11 are encompassed by Formula IVE.
EXAMINER’S RESPONSE
It is duly noted that Applicant asserts that the Conjugates of Compounds 17a and 17b fall within Formula IVE. Applicant’s response is non-persuasive because the issue was not whether or not Compounds 17a and 17b fall within one of the formula as Compounds 17a and 17b were examined (see the office action mailed10/24/2025). The issue was that Applicant removed all formulae and presented very general terminology which was broader than what was presented earlier for examination and for which the scope of claims read.
In regard to the written description rejection, as detailed supra, the pending claim also lack written description.
Improper Markush Rejection
The improper Markush rejection is deemed moot in view of amended claims.
112 Second Paragraph Rejections
The outstanding 112 second paragraph rejections are WITHDRAWN because Applicant amended the claims to overcome the rejection.
NEW GROUNDS OF REJECTIONS
112 Second Paragraph Rejections
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 11-14 and 32-37 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.
Claims 11-14 and 32-37: Independent claim 11 is ambiguous for the following reasons. According to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under 35 USC 112(b), in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed to any known/unknown bis-B10 compound having any known/unknown first closo-decaborate moiety and any known/unknown second closo-decaborate moiety wherein
the first closo-decaborate moiety is covalently linked to any known/unknown trivalent group by any known/unknown first linker group,
the second closo-decaborate moiety is covalently liked to the trivalent group by any known/unknown second linker group,
the trivalent group is covalently linked to any targeting agent, and
the first closo-decaborate moiety and the second closo-decaborate moiety are linked by an astatine atom or an astatine oxide group.
Sivaev et al (Collect. Czech. Chem. Commun., 2010, Vol. 75, No. 11, pages 1149-1199) (see entire document) is made of record to illustrate that there are various closo-decaborate structures and derivatives thereof having distinct characteristics. For example, one may have salts and complexes of [B10H10]2- anion, derivatives containing a boron-halogen bond, derivatives with a boron-carbon bond, derivatives with a boron-nitrogen bond, derivatives with a boron-phosphorus bond, derivatives with a boron-oxygen bond, derivatives with a boron-sulfur bond, derivatives with a boron-selenium bon, and derivatives with a boron-metal bond .
Cao et al (Nature Protocols, 2026, Vol. 21, pages 2328-2363) is made of record to illustration that trivalent linkers encompass a multitude of possible combinations. In particular, Cao et al disclose that trivalent linkers may be homotrivalent, dual ligase heterotrivalent, or dual target heterotrivalent (see page 2330). In addition, Cao et al disclose that there are various potential trifunctional cores that include atom trifunctional cores such as
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and
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; amino acid trifunctional cores
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; multicomponent trifunctional cores such as
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; and ring trifunctional cores such as
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(see page 2331, Figure 3).
Yan (Chinese Journal of Cancer, www.cjcsysu.com, 2013, CACA Chinese Anti-Cancer Association, pages 225-232) is made of record to illustrate that there is a multitude of possible targeting agents that may be conjugated to a structure and targeted to a desired location (see pages 226-227, Table 1).
Thus, the independent claim 11 encompasses a multitude of possible conjugates defined by multiple Markush groups and subgroups thereof. As a result, pending claim 1 encompasses a massive number of distinct variants such that one skilled in the art cannot determine the metes and bounds of the claim. Hence, due to an inability to envision the compounds defined by the Markush groups, the claim is deemed to be vague and indefinite. Furthermore, claims 12-14 and 32-37 which depend upon independent claim 11 are also ambiguous.
Claim 13: The claim is ambiguous because one cannot determine the metes and bounds of species which Applicant is defining as cancer targeting biomolecules.
Claim 14: The claim is ambiguous because of the phrase ‘functional fragment thereof’. In particular, it is unclear what portion of the parent structure is retained in the fragment such that it is a function fragment of a desired antibody.
103 Rejection
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.
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.
Claims 11-14 and 32-36 are rejected under 35 U.S.C. 103 as being unpatentable over Wilbur et al (Bioconjugate Chem., 2007, Vol. 18, pages 1226-1240) in view of Wilbur et al (Nuclear Medicine and Biology, 2010, Vol. 37, pages 167-178).
Wilbur et al (Bioconjugate Chem., 2007, Vol. 18, pages 1226-1240) referred herein as Wilbur et al #1). Likewise, Wilbur et al (Bioconjugate Chem., 2011, Vol. 22, pages 1089-1102) will be referred herein as Wilbur et al #2.
Amended independent claim 11 is directed to a conjugate comprising a bis-B10 compound having a first closo-decaborate moiety and a second closo-decaborate moiety wherein
the first closo-decaborate moiety is covalently linked to a trivalent group by a first linker group,
the second closo-decaborate moiety is covalently liked to the trivalent group by a second linker group,
the trivalent group is covalently linked to a targeting agent, and
the first closo-decaborate moiety and the second closo-decaborate moiety are linked by an astatine atom or an astatine oxide group.
Claim 12 is directed to the conjugate of claim 11 wherein the targeting agent is a biomolecule.
Claim 13 is directed to the conjugate of claim 11 wherein the targeting agent is a cancer-targeting biomolecule.
Claim 14 is directed to the conjugate of claim 11 wherein the targeting agent is an antibody or a functional fragment thereof.
Claim 34 is directed to the conjugate of claim 11 wherein the trivalent group comprises a 1,3,5-trisubstituted phenyl group.
Claim 35 is directed to the conjugate of claim 11 wherein the trivalent group is covalently linked to a targeting agent by a thiourea group.
Claim 36 is directed to the conjugate of claim 1 wherein the astatine atom is 211At.
Wilbur et al (Bioconjugate Chem., 2007, Vol. 18, pages 1226-1240) referred herein as Wilbur et al #1) is directed to cancer targeting biomolecules that are labeled with 211At (see entire document, especially, abstract). In particular, the document discloses the structure
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in Scheme 1, page 1231). While the structure is not radiolabeled in Scheme 1, the structure was labeled with 211At as indicated on page 1234, Table 1. The structure is structurally similar to that of claim 11 because it encompasses a two carborates (nido carborates instead of closo-decaborate), two linker groups, a trivalent group, a targeting containing moiety, and an astatine group (211At):
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. Also, while Wilbur et al #1 does not disclose a closo-bis-decarborate structure (structure containing two decarborates), the document does disclose a single clos-decarborate structure with the same targeting moiety and trivalent group as the bis-nido-caborate in Scheme 1 which is labeled with 211At:
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(see Scheme 2, page 1231 and page 1234, Table 1). Thus, since the structures are structurally similar and conjugated to the same targeting moiety and trivalent group. In addition, the radiochemical yield of 5-Fab is greater than that of 3-Fab’. While the skilled artisan would be motivated to replace the nido-caborate of 3-Fab’ with 5-Fab due to greater radiochemical yield, Wilbur et al #1 disclose that due to difficulties with assessing the number of closo-decaborate derivatives conjugated to the protein when 5-Fab’ was evaluated, resulted in the generation of 6-Fab which was also synthesized and labeled with 211At:
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(see page 1232, Scheme 3 and page 1234, Table 1).
Wilbur et al #2 is made of record for its disclosure of closo-decaborate reagents that are labeled with 211At and incorporate linkers such as a PEG linker(see entire document, especially, abstract; page 1090, Figure 1, Compound 6b; page 1094, right column, third complete paragraph; page 1095, Scheme 2a, Compound 6b). While none of the structures have a bis-caborate structure, Wilbur et al #2 do suggest that one may more than one closo-decaborate structures per antibody conjugated on page 1098, right column, second complete paragraph. While, the discussion focuses on the radiodine labeled conjugate, based on the teachings of the of Wilbur et al #1 which disclosed a bis-nido structure containing overlapping trivalent moiety, antibody, and linker components and the positive results illustrated in Table 1, a skilled artisan would be motivated to incorporate another decaborate structure. Furthermore, since both Wilbur et al #1 (page 1231, Scheme 1; page 1234, Table 1; pages 1234-1235, bridging paragraph; page 1235, Figure 4D) and Wilbur et al #2 (see abstract) disclose the coinjection/coadministration of two caborate structure, it would have been obvious to a skilled artisan at the time of the invention to generate a conjugate with two decaborate components.
For the reasons set forth herein, the pending invention is rendered obvious by the prior art of record as the limitations of claims 11-14 and 32-36 are met.
Note(s): The search was not extended beyond the attachment of 211At to the structure because prior art was found to reject the claims. Thus, claim 37 was not examined.
Claims 11-14 and 32-36 are rejected under 35 U.S.C. 103 as being obvious over Wilbur et al (Bioconjugate Chem., 2007, Vol. 18, pages 1226-1240) in further view of Yawen et al (Journal of Nuclear Medicine, May 2020, Vol. 61, Supplement 1, Abstract 580) and Wilbur et al (Nuclear Medicine and Biology, 2010, Vol. 37, pages 167-178).
The applied reference (Yawen et al) has common inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Wilbur et al (Bioconjugate Chem., 2007, Vol. 18, pages 1226-1240) referred herein as Wilbur et al #1). Likewise, Wilbur et al (Bioconjugate Chem., 2011, Vol. 22, pages 1089-1102) will be referred herein as Wilbur et al #2.
See detailed discussions of Wilbur et al #1 and Wilbur et al #2 supra.
Yawen et al is made of record for its teachings of labeling anibody-B10 (closo-decaborate structures) with 211At. In particular, Yawen et al disclose that the boron cage labeling moiety, isothiocyanato-phenethyl-ureido-clos-decaborate (B10-NCS) may be conjugated to Mabs and labeled with 211At (see pages 1-2, abstract). In particular, it is disclosed that one of the conjugates used is MAb-bis(B10) which contains two B10 moieties (see page 2, ‘Methods’ and ‘Conclusions’).
Thus, based on the teachings of Yawen et al, Wilbur et al #1, and Wilbur et al #2, it would have been obvious to one of ordinary skill in the art to have two close decaborate moieties conjugated covalently linked to a trivalent group by a first and second linker and labeled with astatine because (1) Yawen et al specifically discloses due conjugate: (2) Wilbur et al #1 disclose a structure with a dual caborate attached thereto in combination with a trivalent moiety, targeting agent, and first and second linkers; and (3) Wilbur et al disclose PEG containing linkers that may be used with closo-decaborate structures. Since all of the references are directed to caborate structures that may be radiolabel with 211At, the references may be considered to be within the same field of endeavor. Hence, the reference teachings are combinable.
Withdrawn Claims
Claims 30 and 31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Objection
Claim 37 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Note(s): Claim 37 is only object to as it reads upon Applicant’s elected species. Specifically, while Compounds 17a and 17b are free of the prior art of record, only Compound b was directed to X= AtO.
Comments/Notes
It should be noted that the full scope of pending claim 11 was not searched.
Note(s): It should be noted that no prior art was cited against Applicant’s Compounds 17a and 17b and claim 37 was only examined to the extent that it reads on elected species Compound 17b.
Conclusion
Claims 30 and 31 are withdrawn. Claims 11-14 and 32-36 are rejected. Claim 37 is objected
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.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
August 24, 2026
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