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 7/9/2025 wherein claims 3-7, 10, 15-17, 19, 25, and 27 were canceled and claims 18-24, 26, 28, and 29 were amended. In addition, the Examiner acknowledges receipt of the amendment filed 4/26/2022. The replacement drawing filed 10/25/2022 are acknowledged.
Note(s): Claims 1, 2, 8, 9, 11-14, 18, 20-24, 26, and 28-31 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
Independent claim 1 is directed to compounds of Formula (I):
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81
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wherein the variables X, L, Y, L1, L2, Ar1, and Ar2 are defined therein.
Independent claim 9 is directed to compounds of Formulae (IIA), (IIB), (IIC), and (IID):
Formula (IIA):
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88
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Formula (IIB):
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78
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Formula (IIC):
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84
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and
Formula (IID):
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83
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wherein the variables are defined therein.
Independent claim 11 is directed to compounds of Formulae (IVE), (IVF), (IVG), and (IVH):
Formula (IVE):
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92
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Formula (IVF):
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91
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Formula (IVG):
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95
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and
Formula (IVH):
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102
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wherein the variables are defined therein.
Claim 28 is directed to a method for making an astatine conjugate, comprising reacting a conjugate of claim 10 with an electropositive astatine species.
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
Applicant’s election of Group III (pending claims 11-14, 18, 20-24, and 26) 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 has been treated as an election without traverse (MPEP § 818.01(a)). Thus, the restriction is still deemed proper and is made FINAL.
Applicant elected the species of Figure 25 for initial examination. In the response filed 7/9/2025, Applicant indicated that one was elected Compound 16. However, it appears 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: 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-. Applicant stated that claims 11-14, 18, 20-24, and 26 from Group III read on the elected species.
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 optionally present. Nonetheless, Compounds 17A and 17B were examined and no prior art found to reject the claims. Due to the difficult in understanding the metes and bounds of the pending claims and the lack of written description regarding the claims, a full search of the scope of Group III was not possible.
Withdrawn Claims
Claims 1, 2, 8, 9, and 28-31 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Information Disclosure Statement
The information disclosure statement filed 10/13/2022 was considered.
Specification
The disclosure is objected to because of the following informalities: the structures and text on page 23, line 26, are difficult to read. Applicant is respectfully requested to submit readable copies of the structures and legible text.
Appropriate correction is required.
Written Description Rejection
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, 18, 20-24, and 26 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 of Formulae (IVE) – (IVH) that lack a linker (L). In addition, the pending application does not sufficiently describe the invention as it relates to modifications to an aromatic moiety that are reactive with an electropositive astatine. 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 as 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.
Improper Markush Rejection
Claims 11-14, 18, 20-24, and 26 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Formula (IVE):
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Formula (IVF):
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Formula (IVG):
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and
Formula (IVH):
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are improper because the alternatives defined by the Markush grouping of the variables M, Z, L, Y, L1, L2, Ar1, Ar2, and R individually do not share both a single structural similarity and a common use for the following reasons.
If it is asserted that the formulae individually share a ‘single structural similarity’ where they belong to the same recognized physical or chemical class or to the same art-recognized class, then, the mere existence of astatine (At) in the structures is not structural similarity, but the structures must be considered as a whole. The structures contain the variables M, Z, L, Y, L1, L2, Ar1, Ar2, and R. M is any targeting agent. Z is any group formed from linking the targeting agent to L. L is any linker group. Y is any trifunctional group that links L, L1, and L2. L2 is any linker. Ar1 and Ar2 are any aromatic group that is reactive with an electropositive astatine species or is substituted with a group that makes it reactive with an electropositive astatine atom. R is a halide, hydroxyl, thiocyanate, isothiocyanate, or sulfhydryl. It is duly noted that the pending invention does not teach that the R values encompassed herein are equivalent to one another and would behave/function the same.
According to Symeres ((2023), pp. 1-7, https://symeres.com/linkers-and-conjugation-chemistry/), linkers include cleavable and non-cleavable linkers. Cleavable linkers include those that are peptide-like, pyrophosphate linkers, carbohydrate linkers, PEGylated linkers, and hydrazones. This encompasses Applicant’s variables L, L1, and L2. It is duly noted that the pending invention does not teach that linkers encompassed herein are equivalent to one another and would behave/function the same.
According to Reusch ((2013), 11 pages, https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/react3.htm), aromatic groups include benzene and naphthalene, antracene, phenanthrene, chrysene, pyrene, corannulene, coronene, and hexaheliciene, 1,3-cyclopentadiene, 1,3,5-cycloheptatriene, 1,3,5,7-cyclooctatetraene, pyridine, furan, pyrrole, for example. This encompasses Applicant’s variables Ar1 and Ar2. It is duly noted that the pending invention does not teach that aromatic groups encompassed herein are equivalent to one another and would behave the same.
According to LibreText ((2021), pages 2.4.1 - 2.4.15 (Chapter 2, Section 2.4, 15 pages), https://bio.libretexts.org/Courses/Wheaton_College_Massachusetts/Principles_of_Biochemistry/02%3A_Introduction_to_Biochemistry/2.04%3A_Types_of_Biological_Molecules, there are distinct types of biological molecules that carbohydrates (e.g., glucose, galactose, fructose, starch, glycogen, cellulose, and chitin), lipids, steroids, waxes, proteins, and nucleic acids. This encompasses Applicant’s variable M. It is duly noted that the pending invention does not teach that targeting agents (e.g., biological molecules) encompassed herein are equivalent to one another and would behave/function the same.
Based on Formulae (IVE) – (IVH) and the teachings of Symeres, Reusch, and LibreText, a multitude of structurally distinct species are encompassed by claims 11-14, 18, 20-24, and 26. The structures do not contain a common core but comprise a wide variety of rings optionally containing one or more heteroatom and carbon atom combinations (linear/branched as well as substituted and unsubstituted structures all of which are optionally substituted with a heteroatom) that may be linked in various orientations with halogens and alkyl groups, for example.
In the instant case, if it is asserted that the claims share a common utility, namely they are used in the treatment of a disease or condition, the genus does not share a substantial structural feature essential to the utility which is a feature that is essential to the activity/function of the claimed species. The only component that is probably consistent from one formula to the other is an astatine (At). As a result, such a grouping would be repugnant to scientific classification because the astatine atom alone is not responsible for the utility of the entire molecule. In addition, the wide variety of rings optionally containing one or more heteroatoms connected directly or indirectly to the carbon-carbon bond does not allow the genus to have an art recognized classification. Hence, the Markush grouping is improper.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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, 18, 20-24, and 26 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, 18, 20-24, and 26: Independent claim 11 is ambiguous because in the election of the elected species, Applicant discloses that the variable L is not present. Thus, it is unclear whether or not L is an optionally present or not. In addition, claim 11 is ambiguous for the following reasons: (1) It is unclear what the variable Z is because it has no specific values, but instead states that it is a group formed from linking the targeting agent to L; (2) it is unclear what trifunctional group Applicant is referring to that is links L, L1, and L2; and (3) it is unclear what aromatic group(s) Applicant is referencing that is reactive with an electropositive astatine species. (4) Still, the claim is ambiguous because it is unclear what substituted group Applicant is referring to that makes it reactive with an electropositive astatine group. Since claims 12-14, 18, 20-24, and 26 depend upon independent claim 11 for clarity, those claims are also vague and indefinite.
Claim 14: The claim is ambiguous because it is unclear what ‘functional fragment of an antibody’ Applicant is referring to that are compatible with the instant invention. In particular, it is unclear what portion of the parent antibody is necessary to generate a functional fragment of an antibody.
Claims 21 and 22: The claims are ambiguous because it is unclear what modification yield a reactive moiety with electropositive astatine species.
Comments/Notes
It should be noted that while no prior art is cited against the pending invention, the metes and bounds of the claim were difficult to ascertain as detailed supra. Applicant is respectfully requested to clarify the invention in order that the claims of the elected invention may be thoroughly searched.
Applicant elected the species for initial examination that is present in Figure 25. The structures in Figure 25 (Compounds 16, 17A, and 17B) are difficult to read.
Conclusion
Claims 1, 2, 8, 9, and 28-31 are withdrawn. Claims 11-14, 18, 20-24, and 26 are rejected.
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
October 22, 2025