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 3/13/2026 wherein claims 14 and 15 were amended and claims 16-18, 20, 24-26, 28-36, 38-45, and 47-49 were canceled. In addition, the Examiner acknowledges receipt of the amendment filed 3/20/2023 wherein the claims and specification were amended.
Note(s): Claims 1-15, 19, 21-23, 27, 37, and 46 are pending.
Priority
This application is a 371 of PCT/US2021/051322 filed 9/21/2021;
PCT/US2021/051322 claims benefit to PRO 63/242,315 filed 9/9/2021; and PCT/US2021/051322 claims benefit to PRO 63/081,632 filed 9/22/2020.
Note(s): The earliest effective filing date is 9/22/2020 because the pending invention is fully disclosed in provisional application 63/081,632.
Claim Interpretation
Independent claim 1 is directed to a compound or pharmaceutically acceptable salt thereof comprising a pH insertion peptide (pHLIP) wherein the pHLIP comprises a C-terminus and an N-terminus and X1 covalently attached to a heteroatom side chain of an amino acid residue of the pHLIP and wherein the amino acid residue is from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 residues from the C-terminus or the N-terminus, wherein X1 is Formula (I), Formula (II), or Formula (III)
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372
418
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;
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480
425
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; or
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445
434
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and all other variables are as defined in independent claim 1.
Applicant’s Election
Applicant's election without traverse of Group I (pending claims 1-15, 19, 21-23, and 46) filed 3/13/2026 is acknowledged. Hence, the restriction requirement is still deemed proper and is therefore made FINAL.
Applicant elected the species wherein X1 is Formula I,
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372
396
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, and pHLIP is [89Zr]Zr-DFO-cys-Var3pHLIP, thus, the compound is (D-Ala)-(D-Cys[X1])-(D-Asp)-(D-Asp)-(D-Gln)-(D-Asn)-(D- Pro)-(D-Trp)-(D-Arg)-(D-Ala)-(D-Tyr)-(D-Leu)-(D-Asp)-(D-Leu)-(D-Leu)- (D-Phe)-(D-Pro)-(D-Thr)-(D-Asp)-(D-Thr)-(D-Leu)-(D-Leu)-(D-Leu)-(D- Asp)-(D-Leu)-(D-Leu)-(D-Trp) (SEQ ID NO. 9);
Z1, Z2, and Z3 are each hydrogen; W1 is
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115
194
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; and n is 2; M1 is 89Zr4+. The diseased tissue of interest is tumor tissue.
Applicant’s elected species was searched and no prior art was found to reject the claims. The full scope of Group I was searched.
Withdrawn Claims
Claims 27 and 37 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 statements filed 3/20/2023 and 11/21/2024 were considered.
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 1-5, 7-10, 13-15, 21-23, and 46 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 low pH insertion peptides configured to localize to an extracellular environment having a pH that is lower than 7.4 that is conjugated to Formulae I, II, or III other than SEQ ID Nos. 1-241. 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.
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 1-15, 19, 21-23, and 46 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 1-5, 7-10, 13-15, 21-23, and 46: Independent claim 1 is ambiguous because (1) it is unclear what low pH insertion peptides Applicant is referencing that may be configured to localize to an extracellular environment that are compatible with Formula I, Formula II, and Formula III. (2) In line 14, of claim 1: it is unclear if the phrase (i.e., providing an oxygen anion)’ is actually a limitation of the claim or not (see MPEP 2173.05(d)). (3) It is unclear what is attached to the oxygen atom when Z1-Z11 are lone pairs of electrons (see claim 1, line 14 and claim15, line 10). What is the actual compound that is being claim as the valance is incomplete.
Since claims 2-5, 7-10, 13-15, 21-23, and 46 read on independent claim which is unclear, the dependent claims are also vague and indefinite.
Claims 1-15, 19, 21-23, and 46: Independent claim 1 is ambiguous because of the phrase ‘configured to localize to an extracellular environment having a pH that is lower than 7.4’ (see lines 2-3) is an active step. According to MPEP 2173.05(p), a single claim directed to both a product and method steps involving such product is indefinite. In particular, the claim is indefinite because while the claim initially sets forth a product (compound comprising a pHLIP and X1), the claim limitation is not directed to the product, but rather to actions (configuration that results in localization to an extracellular environment having a pH that is lower than 7.4) involving the product which creates confusion as to when direct infringement occurs. Specifically, it is unclear whether infringement occurs when one has a product comprising the components or when the active steps occurs and results in a particular action.
Since claims 2-15, 19, 21-23, and 46 depend upon independent claim 1 for clarity, those claims are also vague and indefinite.
Claims 2 and 3: The claims are ambiguous because of the phrase ‘is configured to localize to an extracellular environment having a pH that is lower than 7.1’ and ‘is configured to localize to an extracellular environment’. First, it is unclear what specific pHLIP peptides Applicant is referring to that meet those requirements. Secondly, those phrases are active steps. According to MPEP 2173.05(p), a single claim directed to both a product and method steps involving such product is indefinite. In particular, the claim is indefinite because while the claim initially sets forth a product (compound comprising a pHLIP and X1), the claim limitation is not directed to the product, but rather to actions (configuration that results in localization to an extracellular environment) involving the product which creates confusion as to when direct infringement occurs. Specifically, it is unclear whether infringement occurs when one has a product comprising the components or when the active steps occurs and results in a particular action.
Claim 15, line 7: The phrase ‘M1 is independently at each occurrence the radionuclide’ is ambiguous because each formula only contains one M1 variable. The use of ‘independently at each occurrence’ indicates that the formulae contain multiple M1. According the claim language, one has individual compounds and those individual compounds have a single M1.
Comments/Notes
In claim 6, lines 25 and 29, the right parenthesis is missing after the sequence identification number.
In claim 15, line 1, it is not necessary to insert ‘the’ before ‘X1’.
Applicant is respectfully reminded that the phrase ‘for detecting a tissue comprising an extracellular environment having a pH that is lower than 7.4’ is the intended use of the composition of claim 23. Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.
It should be noted that no prior art is cited against the pending invention. However, Applicant must address and overcome the 112 first and second paragraph rejections above. In particular, the claims are allowable over the prior art of record because the prior art neither anticipates nor renders obvious the compounds or salts thereof as set forth in independent claim 1. The closest art is Applicant’s own work which is present in WO 2018/023098. Specifically, the pending invention is distinguished over WO 2018/023098 because the document neither teachers nor renders obvious Formula I, Formula II, or Formula III in combination with a pH insertion peptide.
Similarly, Bhatia et al (WO 2020/150560 and US Patent No. 11,835,522) disclose compounds and derivatives thereof that overlap with the pending invention like Applicant’s own work (WO 2018/023098). In addition, like WO 2018/023098, Bhatia et al neither teaches nor renders obvious Formula I, Formula II, or Formula III in combination with the pH insertion peptide.
Conclusion
Claims 1-15, 19, 21-23, and 46 are rejected. Claims 27 and 37 are withdrawn.
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
May 7, 2026
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