Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 1-19 are pending. t
Priority
This application is a CON of 17383577 filed 7/23/2021 (now US Patent No. 12,064,491); 17/383,577 is a CON of 16/580,990 filed 9/24/2019 (now US Patent No. 11,083,805);
16/580,990 is a CON of 15/817,776 filed 11/20/2017;
15/817,776 is a CON of 14/431,096 filed 3/25/2015 (now US Patent No. 9,839,703)
14/431,096 is a 371 of PCT/US2013/061712 filed 9/25/2013; and
PCT/US2013/061712 claims benefit to PRO 61705513 filed 9/25/2012.
Note(s): The earliest effective filing date is 9/25/2012 because the pending invention is fully supported in the parent applications.
Claim Interpretation
Independent claim 1 is directed to a GRPR-antagonist of the general formula: MC-S-P wherein: at least one (radio)metal (M) and a chelator (C) which stably binds M; alternatively MC may represent a Tyr- or a prosthetic group carrying a (radio)halogen; S is an optional spacer covalently linked between the N- terminal of P and C and may be selected to provide a means for (radio)halogenation; P is a GRP receptor peptide antagonist of the general formula: Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-CO-Z;
Xaa1 is not present or is selected from the group consisting of amino acid residues Asn, Thr, Phe, 3-(2-thienyl)alanine (Thi), 4-chlorophenylalanine (Cpa), a-naphthylalanine (alpha-Nal), beta-naphthylalanine (beta-Nal), 1,2,3,4- tetrahydronorharman-3-carboxylic acid (Tpi), Tyr, 3-iodo- tyrosine (o-I-Tyr), Trp, or pentafluorophenylalanine (5-F-Phe) (all as L- or D-isomers);
Xaa2 is Gln, Asn, or His
Xaa3 is Trp or 1,2,3,4-tetrahydronorharman-3-carboxylic acid (Tpi)
Xaa4 is Ala, Ser, or Val
Xaa5 is Val, Ser, or Thr
Xaa6 is Gly, sarcosine (Sar), D-Ala, or beta-Ala
Xaa7 is His or (3-methyl)histidine (3-Me)His
Z is selected from -NHOH, -NHNH2, -NH-alkyl, - N(alkyl)2, or -O-alkyl or
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wherein X is NH (amide) or O (ester) and R1 and R2 are the same or different and selected from a proton, a (substituted)alkyl, a (substituted) alkyl ether, an aryl, an aryl ether or an alkyl, halogen, hydroxyl, or hydroxyalkyl substituted aromatic group.
Applicant’s Election
Applicant's election without traverse of Group I (pending claims 1-15 and 19) filed 6/26/2025 is acknowledged. Hence, the restriction requirement is still deemed proper and is therefore made FINAL.
Applicant elected the species
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conjugated to 177Lu for initial examination. For Applicant’s formula MC-S-P, the variables have the following values: M is 177Lu, C is the chelator DOTA, S is p-Aminobenzylamine-diglycolic acid, and P is DPhe-Gln-Trp-Ala-Val-Gly- His-CO-NH-CH(CH2-CH(CH3)2)2. Applicant further elects a therapeutic radionuclide which is 177Lu, a diagnostic radionuclide which is 67Ga, and cancer of interest is breast cancer.
Initially, Applicant’s elected species was searched and no prior art was found which could be used to reject the claims. While the search was expanded over independent claim 1, the metes and bounds of the claim could not be determined due to the numerous 112 rejections as detailed below. In addition, for many of the dependent claims, they were improper multiple dependent claims and as such the clarity of the claimed invention was not possible.
Only claims 1-15 and 19 (Applicant’s elected Group I) were examined.
Withdrawn Claims
Claims 16-18 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 7/15/2024 was considered.
Specification
The disclosure is objected to because of the following informalities: the structures appearing on pages 7, 19, and 31-33 are not readable. It is difficult to read some of the atoms, bonds, and/or subscripts.
Appropriate correction is required.
Improper Multiple Dependent Claims
Claims 5-15 and 19 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims could not be thoroughly examined.
Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8, 12-15, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15, 18, and 29 of copending Application No. 17/283,462 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to
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wherein M is 177Lu, 68Ga, or 111In. Thus, both inventions disclose overlapping GRPA antagonists.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 9,839,703. Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to
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wherein M is various metals including 99mTc, 186Re, 67Ga, 177Lu, 68Ga, and 111In, for example. In addition, patented claim 1 is directed to species other than Applicant’s elected species which are encompassed by the formula MC-S-P as set forth in pending independent claim 1. Hence, both inventions disclose overlapping GRPR antagonists.
Claims 1-15 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,064,489. Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to GRPR antagonist which may be conjugated to various metals including 186Re, 188Re, 177Lu, 68Ga, and 164Cu, for example. In addition, patented claim 1 is directed to other species encompassed by the formula MC-S-P as set forth in pending independent claim 1. Furthermore, while the patented claim is directed to a method, the compounds used therein are GRPR antagonists. Hence, both inventions disclose overlapping GRPR antagonists.
Claims 1-8, 12-15, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 7-9 of U.S. Patent No. 12,064,490. Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to
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wherein M is 177Lu. In addition, patented claim 1 is directed to species other than Applicant’s elected species which are encompassed by the formula MC-S-P as set forth in pending independent claim 1. Hence, both inventions disclose overlapping GRPR antagonists.
Claims 1-8, 12-15, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 7-9 of U.S. Patent No. 12,064,491. Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to
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wherein M is a metal such as 68Ga (see patented claim 2). In addition, patented claim 1 is directed to species other than Applicant’s elected species which are encompassed by the formula MC-S-P as set forth in pending independent claim 1. Hence, both inventions disclose overlapping GRPR antagonists.
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 1-15 and 19 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 instant application does not sufficiently describe the invention as it relates to prosthetic groups carrying a (radio)halogen that are compatible with the pending invention. 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 and 19 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 1-15 and 19: Independent claim 1 is ambiguous for the following reasons:
(1) the claim recites the limitation "the general formula" in lines 1 and 10-11. There is insufficient antecedent basis for this limitation in the claim.
(2) The phrase “stably binds” in line 5 is a relative phrase which renders the claim indefinite. The phrase is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
(3) The phrase “(radio)metal” is indefinite because it is unclear whether or not (a) the phrase should be interpreted as “radiometal” or (b) if “(radio)metal” encompasses “a radiometal” and a “metal” (non-radioactive metal). The presence of the parentheses around “radio” result in the term being indefinite. This indefiniteness also applies to the phrase “(radio)halogenation” in line 9.
(4) The claim as written is ambiguous because it is unclear what prosthetic group(s) Applicant is referring to that carry a (radio)halogen.
(5) The phrase ‘may be’ in line 8 is not a positive limitation. The phrase implies that the definition of what follows is not definite and may or may not be selected to provide a means for (radio)halogenation
(6) The phrase ‘to provide a mean for (radio)halogenation’ is vague and indefinite as it is unclear what specific linker values Applicant intends to include.
(7) The claim is ambiguous because it is difficult to read some of the subscripts appearing in the claim (see lines 12 and 27-28).
(8) The Markush groupings are missing the term ‘or’ before the last element. As a result, it is unclear whether or not Applicant intended to incorporate additional text or not. See lines 18, 20, 21, 22, 23, 24, 25, and 26.
(9) It is unclear whether or not text is missing from the Markush groupings. There is a comma between the two substances present. See lines 21, and 26.
(10) Lines 30-31 are ambiguous because the definition of X is not consistent with what is present in the structure of line 30. Specifically, “NH (amide)” and “O (ester)” are confusing. “O” in the structure does not result in an ester as the general formula of an ester is
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wherein R and R’ are carbon containing substances and a double bonded carbon is present. Similarly, the phrase “NH (amide)” is confusing. The general formula of an amide (e.g., primary amide) is
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wherein R is a carbon containing substance and a double bonded carbon is present. Thus, the phrases are confusing.
(11) It is unclear whether or not text is missing from the term “alkyl-“ appearing in line 34. Should there be text after the hyphen?
(12) In line 4 of the claim, what is the purpose or meaning of the hyphen at the beginning of the sentence? Did Applicant intend to remove it?
Since claims 2-15 and 19 depend upon independent claim 1 for clarity, those claims are also vague and indefinite.
Claim 2: The claim reads on a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 incorporates the broad definition of the variable Z recited in independent claim 1, and the claim also recites preferred embodiment which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 2: The claim is ambiguous because it is difficult to read some of the atoms and subscripts. In addition, some of the structure contain does in the variable definitions of ‘m’ and ‘n’. Still some of the variable definitions of ‘m’ and ‘n’ contain “#”. See lines 4-19.
Claim 5: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation that the radiohalogen is suitable for diagnostic or therapeutic use (see line 3), and the claim also recites preferred radionuclides (see lines 3-9) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 5: The claim is ambiguous because of “a.o..” which is in line 9.
Claim 7: The claim is ambiguous because it is unclear what derivatives of DTPA, NOTA, DOTA, and TETA based mono- and bifunctional chelators Applicant is referring to that are compatible with the pending invention. In particular, it is unclear what portion of the parent structures are present in the derivatives.
Claims 8 and 11: The claim is ambiguous because it does not contain a period at the end of the sentence. Thus, it is unclear whether or not Applicant intended to incorporate additional text or not.
Claim 10: The claim is ambiguous because it is unclear what derivatives of acyclic tetraamine-, cyclam, PnAO, P22, N2S2, N3S, HYNIC, and co-ligand based chelators Applicant is referring to that are compatible with the pending invention. In particular, it is unclear what portion of the parent structures are present in the derivatives.
Claim 10: The claim is ambiguous because of the “/” mark in the claim between HYNIC and co-ligand based chelators. If the two are equivalent, it is respectfully suggested that one or the other phrase be used. In addition, the claim is ambiguous because of the reference to “forming organometallic complexes via the tricarbonyl technology” (lines 6-7).
Claim 11: The claim is ambiguous because the variable Xaa is not defined.
Claim 12: The claim is ambiguous because it is unclear what particular spacers Applicant is referring to that may be selected to provide a means for (radio)iodination.
Claim 13: The claim recites the limitation "the formula" in lines 3, 10, and 17. There is insufficient antecedent basis for this limitation in the claim.
Claim 13: The dots appearing in the variable definitions of the variable “n” are indefinite (see lines 11 and 13).
Claim 13 (lines 16-29): A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation that the (1) PEG spacers have various lengths and (2) the alpha and beta amino acids are single or in homologous chains of various lengths and the claim also recites specific PEG spaces and specific chains therein which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 14: The claim recites the limitation "the formula" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 15: The claim is ambiguous because it is unclear whether Applicant intended the claim to be a product or method of use claims.
Comments/Notes
While no prior art is cited in the pending invention, it should be noted that the claims could not be thoroughly searched due to the various improper multiple dependent claims, variables/terms with indefinite values/meaning, and the numerous 112 rejection issues present.
The lined through textbook on the information disclosure statement could not be located. Applicant is respectfully requested to provide the document for review.
The Examiner is aware of numerous applications with similar subject matter. However, while every effort has been made to review all applications containing overlapping subject matter, some applications may have been missed. Thus, Applicant is respectfully requested to submit all serial numbers of applications containing overlapping subject matter for review by the Examiner.
Conclusion
Claims 1-15 and 19 are rejected. Claims 16-18 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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 8, 2025