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 .
Summary
Claims 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are pending in this office action. Claims 3, 8, 11, 14, 16, 20, 22, 27-28, and 30-33 are cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on June 10, 2024 is a 371 of PCT/US2022/081098 filed December 7, 2022, which in turn claims domestic priority to provisional patent application 63/287,494 filed December 8, 2021.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on October 8, 2024 is acknowledged. A signed copy of the document is attached to this office action.
Sequence Rule Compliance
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because claims 5 and 15 recite the sequence DGlu-DGlu-βAla-βAla plus a portion of the structure includes D-Glu-b-Ala-b-Ala-Ile.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are objected to because of the following informalities:
Claims 1 and 12: Please ensure within variable X that the bonds are on one line together [-NHC(NH)-] and not separate lines. Also please designate -(O)C(NH)- instead of -OC(NH)- indicating a ketone group rather than an ether moiety. Additionally, please designate the bonding order for all variables, for example, which end of -NHC(O)- is attached to the nitrogen of the ring and which end is attached to L. The Examiner is unsure of the structure for -OC(NH)-, is it O=C(NH)? If so, then it should be written
-(O=C)(NH)-. Please designate double bonds as “=” to remove any ambiguity within the structures.
Dependent claims 2, 4-7, 9-10, 13, 15, 17-19, 21, 23-26, and 29 are included here because they fail to cure the defects of independent claims 1 and 12.
Claims 5 and 15: Please identify the acronyms AEA and AEEA. The Applicant has used the three-letter amino acid codes to define the many of the Markush Group members (for example, Glu-Gly-Gly), but AEA and AEEA are not as familiar to a skilled artisan as the natural amino acids.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 7, 10, and 23 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.
The Applicant refers to the specification for a list of compounds within claims 7, 10, and 23. Please include all relevant structures within each claim. By including these structures, the claims will be complete. As they written now, the claims are unclear and indefinite [see MPEP 2173].
Claim Rejections - 35 USC § 103
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 non-obviousness.
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 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Goggi et al. (Molecular Imaging and Biology, 2020) in view of Hiscock et al. (WO2005/053752A2), Mahmood et al. (WO2018/005926A1), and Subbaiah et al. (Journal of Medicinal Chemistry, published September 2021).
[The Examiner is going to introduce each reference and then combine them in the rejection of the instant claims.]
1. Goggi et al.
Goggi et al. is considered the closest prior art to the present invention as it teaches granzyme B PET imaging of immune checkpoint inhibitor combinations in colon cancer phenotypes (see title). Also, Goggi et al. disclose immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes.
Procedures: We have assessed the ability of a fluorine-labelled peptide, [18F]AIF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AIF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations.
Results: [18F]AIF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSl-high phenotype in MC38 tumours.
Conclusions: [18F]AIF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICls administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation (see abstract).
2. Hiscock et al.
Hiscock et al. teach novel imaging agents (see title). Additionally, Hiscock et al. disclose that the present invention relates to diagnostic imaging agents for in vivo imaging. The imaging agents comprise a synthetic caspase-3 inhibitor labelled with an imaging moiety suitable for diagnostic imaging in vivo. The invention also provides pharmaceutical and radiopharmaceutical compositions comprising the imaging agents, together with kits for the preparation of the radiopharmaceuticals. Also described are chelator conjugates of the caspase-3 inhibitor, which are suitable for the preparation of imaging agents comprising a radioactive or paramagnetic metal ion. The imaging agents are useful for the diagnostic imaging and or therapy monitoring in vivo of various disease states where caspase-3 is involved (see abstract).
3. Mahmood et al.
Mahmood et al. teach granzyme B directed imaging and therapy (see title). In addition, Mahmood et al. disclose compounds useful for imaging granzyme B. An exemplary compound provided herein is useful as a radiotracer for position emission tomography (PET) and/or single photon emission tomography (SPECT) imaging. Methods of imaging granzyme B, combination therapies, and kits comprising the granzyme B imaging agents are also provided (see abstract).
4. Subbaiah et al.
Subbaiah et al. teach bioisosteres of the phenyl ring: recent strategic applications in lead optimization and drug design (see title). Furthermore, Subbaiah et al. disclose that the benzene moiety is the most prevalent ring system in marketed drugs, underscoring its historic popularity in drug design either as a pharmacophore or as a scaffold that projects pharmacophoric elements. However, introspective analyses of medicinal chemistry practices at the beginning of the 21st century highlighted the indiscriminate deployment of phenyl rings as an important contributor to the poor physicochemical properties of advanced molecules, which limited their prospects of being developed into effective drugs. This perspective deliberates on the design and applications of bioisosteric replacements for a phenyl ring that have provided practical solutions to a range of developability problems frequently encountered in lead optimization campaigns. While the effect of phenyl ring replacements on compound properties is contextual in nature, bioisosteric substitution can lead to enhanced potency, solubility, and metabolic stability while reducing lipophilicity, plasma protein binding, phospholipidosis potential, and inhibition of cytochrome P450 enzymes and the hERG channel (see abstract).
Combination of Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al.
Regarding instant claim 1, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach a pharmaceutical compound specific to granzyme B. The necessary citations within Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. that correspond to instant claim 1 are compiled within Table I.
Table I
Instant Claim 1
Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. Citations
A compound, or a pharmaceutically acceptable salt thereof, wherein he compound is of formula (I):
Goggi et al. disclose (see abstract; page 1393, figure 2; conclusions) mNOTA-GZP
(NOTA-b-Ala-Gly-Gly-lle-Glu-Phe-Asp-CHO) and its 18F-Al-labelled variant, [18F]AIF-mNOTA-GZP:
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The compound targets (intra-tumoral) granzyme B and is used for PET imaging the immune response in a subject in response to treatment with immune checkpoint inhibitors (see title and abstract within Goggi et al.).
Hiscock et al. (see pages 25, line 19; claims 12, 22) disclose the oxoazepinoindoline compound, Indun A, with the structure:
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The compound is used as a diagnostic imaging agent in vivo comprising a synthetic caspace-3 inhibitor.
Hiscock et al. disclose conjugates comprising a synthetic caspase-3 inhibitor linked to a chelating agent (see abstract within Hiscock et al.). Caspace-3 inhibitors comprising a covalently bound 18F-label are also disclosed (see page 6, lines 1-4 within Hiscock et al.).
Mahmood et al. disclose (see claims 1, 10, 16) granzyme B-binding conjugates comprising structures (see claim 62):
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that resemble parts (same annealed ring system, different substituents) of formula (I) of present application. Mahmood et al. disclose a general formula of A-B-C (see page 1, line 25 within Mahmood et al.). Where A comprises one or more imaging agents, B is an optional linking group; and
C is a group that binds granzyme B (see page 2, lines 5-7 within Mahmood et al.). Additionally, C is selected from the group consisting of a polypeptide that binds granzyme B, an antibody that binds granzyme B, an antibody fragment that
binds granzyme B, and a small organic molecule that binds granzyme B (see page 7, lines 16-18 within Mahmood et al.). Thus, allowing for the substitution of the polypeptide portion of Goggi et al. with the oxoazepinoindoline ring system and lactone moiety of Hiscock et al. (see below).
DESIGN OF ANALOGUES
Combination of the structures supplied by Goggi et al. and Hiscock et al. afford the template to generate targets within this series:
Goggi et al.:
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The blue portion of the peptide would be substituted by the oxoazepinoindoline ring and lactone moiety of Indun A (within Hiscock et al.). The red portion is the “linker” which is covalently bonded to a chelating group.
Hiscock et al.:
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Neither of the disclosed structures comprises a piperazine or piperidine unit as a substitute for an aryl ring. The skilled person is aware that the substitution of a phenyl group by a piperidine or piperazine moiety is a common medicinal chemistry strategy to modulate the pharmacological properties of a compound, such as target affinity, selectivity, solubility, or pharmacokinetic behavior (see for example, Tables 29 and 40 in Subbaiah et al.).
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It would have been obvious to one of ordinary skill in the art to combine the teachings of Goggi et al., Hiscock et al., and Mahmood et al. prior to the effective filing date of the claimed invention, as all references are directed to pharmaceutical targeting compounds granzyme B. Substitution of the aryl ring with a piperidine or piperazine ring as suggested by Subbaiah et al. is standard protocol within medicinal chemistry for a skilled artisan (POSITA; person having ordinary skill in the art). The motivation to combine the four references would be to create imaging and therapeutic agents which target granzyme B and incorporates a nitrogen containing ring system (piperidine or piperazine).
Regarding instant claims 2, 4, 6 and 17, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach the compound, or the pharmaceutically acceptable salt thereof, of instant claim 1, wherein the compound is of formula (Ia):
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and wherein A, Z, Y, X, and L are each defined as in instant claim 1.
Please see the discussion and citations within instant claim 1 for the necessary rejection text. The analogues disclosed by Mahmood et al. already contain the amino acid isoleucine. Furthermore, the [18F]AIF-mNOTA-GZP derivative disclosed by Goggi et al. comprises a b-Ala-Gly-Gly-lle amino acid linkage prior to the chelating group NOTA.
Regarding instant claims 5 and 15, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach wherein L has an appropriate amino acid sequence.
Goggi et al. disclose the linker sequence of b-Ala-Gly-Gly. This does not meet the instant claim 5 limitation. However, PTO-892 NPL X disclose the use of g-Glu as a linker (see abstract within PTO-892 NPL X). Furthermore, PTO-892 NPL W disclose the use of Gly-rich linkers (see abstract within PTO-892 NPL W). Therefore, a skilled artisan (POSITA) would incorporate a g-Glu residue into the linker portion of the analogue under standard conditions.
Regarding instant claims 7 and 10, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach the compound, or the pharmaceutically acceptable salt thereof of instant claim 1, wherein the compound is of formula (Ib-A):
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and wherein A and L are each defined as in instant claim 1.
Please see the discussion and citations within instant claims 1-2, 4, 6, and 17 for the necessary rejection text establishing of the small molecule oxoazepinoindoline ring system and lactone moiety bonded to the amino acid isoleucine. A skilled artisan (POSITA) could generate the “western” portion of the molecule starting from commercially available piperidin-4-yl methanol (CAS# 6457-49-4) and installing the appropriate synthetic groups (alkylation, oxidation, and reductive amination). This chemistry is straightforward and robust. In a similar fashion, the piperizane-4-yl methanol variant is also commercial (CAS# 90324-69-9) and after proceeding through an identical synthetic pathway, would obtain the piperazine variant.
Regarding instant claims 12, 13, and 21, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (II):
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and wherein A, Z, Y, X and L are each defined as in instant claim 1, and M is a metal or a metal linked to a radioisotope.
Please see the discussion and citations within instant claim 1 for the necessary rejection text. Goggi et al. disclose the 18F-Al-labelled variant, [18F]AIF-mNOTA-GZP wherein:
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Regarding instant claims 18 and 19, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach wherein M is non-toxic, and wherein the metal is a radioisotope of Gallium (Ga).
Mahmood et al. disclose non-toxic radioisotopes selected from the group consisting of …68Ga… (see page 78, lines 5-6 within Mahmood et al.).
Regarding instant claim 25, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach a pharmaceutical composition comprising a compound of instant claim 12, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
Mahmood et al. disclose pharmaceutical compositions which contain, as the active ingredient, a compound provided herein, or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers (excipients) (see page 88, lines 9-11 within Mahmood et al.).
Regarding instant claim 26, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach a method of imaging granzyme B in a tissue, the method comprising: (i) contacting the compound or the pharmaceutically acceptable salt thereof, of instant claim 12, with a tissue suspected of comprising granzyme B, and (ii) imaging the tissue based on radioisotope signals released from the compound or the pharmaceutically acceptable salt thereof, optionally further comprising monitoring an immune response in the subject based on the imaging of granzyme B, optionally wherein the radioisotope contained in the compound or the pharmaceutically acceptable salt thereof, is 18F or 68Ga, and optionally wherein the contacting step is performed by administering the compound, or the pharmaceutically acceptable salt thereof, to a subject in need thereof.
Goggi et al. disclose the imaging results with the 18F-Al-labelled variant, [18F]AIF-mNOTA-GZP (see abstract and Figure 2 within Goggi et al.) following the protocol of instant claim 26. In addition, please see the discussion and citations within instant claim 1 for the necessary rejection text.
Regarding instant claim 29, Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. teach wherein the subject is on a treatment for an immunoregulatory abnormality selected from the group consisting of an autoimmune disorder, an inflammatory disorder, a skin disorder, a cancer, and a cardiovascular disorder, optionally wherein the immunoregulatory abnormality is a cancer, and optionally wherein treatment comprises one or more additional therapeutic agents, which are selected from the group consisting of anti-inflammatory agents, steroids, immunotherapy agents, chemotherapeutic agents, and therapeutic antibodies.
Mahmood et al. disclose the administration of a therapeutic agent for the treatment of a designated disease (see claims 96-99 within Mahmood et al.) in agreement with the instant claim 29 protocol.
Analogous Art
The Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. references are directed to the same field of endeavor as the instant claims, that is, a pharmaceutical composition that targets granzyme B for imaging and therapeutic purposes, as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the polypeptide pharmaceutical composition targeting granzyme B disclosed by Goggi et al., using the teachings of Hiscock et al., Mahmood et al., and Subbaiah et al. in order to arrive at the subject matter of the instant claims.
The Goggi et al., Hiscock et al., and Mahmood et al. references all have considerable overlap in the granzyme B radionuclide imaging and therapeutic arts. Furthermore, Subbaiah et al. offers medicinal chemistry support for the substitution of an aryl ring with a nitrogen ring system. In this instance, Goggi et al. supplies the template for the polypeptide pharmaceutical composition that targets granzyme B, Hiscock et al. and Mahmood et al. supplies the oxoazepinoindoline and lactone portion of a granzyme B targeting derivative, while Subbaiah et al. supplies support for the substitution of an aryl ring with either a piperidine or piperazine ring system. All references are directed to granzyme B radionuclide imaging and therapy or analogue development. These citations therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the four references when seeking to develop an aryl modified granzyme B pharmaceutical composition.
Given these teachings, a POSITA would have been motivated to combine the polypeptide template for the granzyme B targeted pharmaceutical composition as disclosed by Goggi et al., the oxoazepinoindoline and lactone portion of a granzyme B targeting derivative disclosed by Hiscock et al. and Mahmood et al., and the support for the substitution of an aryl ring with either a piperidine or piperazine ring system.
The modification constitutes a simple substitution of one known element for another to obtain a predictable result [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar composition in the same way [MPEP §2143(I)(C)].
The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR].
The combination of the polypeptide pharmaceutical composition that targets granzyme B taught by Goggi et al. along with the use of the necessary claim limitations taught by Hiscock et al., Mahmood et al., and Subbaiah et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
Furthermore, the additional claim limitations taught by Hiscock et al., Mahmood et al., and Subbaiah et al. would have been viewed by a POSITA as routine design optimizations or known modifications for granzyme B targeted pharmaceutical compositions. The motivation to combine the four references would be to create imaging and therapeutic agents which targets granzyme B and incorporates a nitrogen containing ring system. Implementing these features in Goggi et al.’s polypeptide pharmaceutical composition that targets granzyme B would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Goggi et al., Hiscock et al., Mahmood et al., and Subbaiah et al. provides all the elements of the claimed invention. The resulting granzyme B targeted pharmaceutical composition for both imaging and therapeutic uses, constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1-30 of co-pending Application No. 18/736,979 (reference application) in view of Mahmood et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Application ‘979 encompass compounds specific to granzyme B and uses thereof.
The difference between the instant claims and that of Application ‘979 is the use of toxic radioisotopes.
However, Mahmood et al. teach granzyme B directed imaging and therapy (see title). In addition, Mahmood et al. disclose compounds useful for imaging granzyme B. An exemplary compound provided herein is useful as a radiotracer for position emission tomography (PET) and/or single photon emission tomography (SPECT) imaging. Methods of imaging granzyme B, combination therapies, and kits comprising the granzyme B imaging agents are also provided (see abstract).
It would have been prima facie obvious to provide toxic metal radionuclides with application ‘979 as suggested by Mahmood et al. (see page 7, lines 1-4 within Mahmood et al.). There would have been a reasonable expectation of success in doing so as both Mahmood et al. and Application ‘979 are to granzyme B directed imaging and therapy.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-18, 21-24, 28, 31-32, and 37 of U.S. Patent No. 12,551,582 in view of Subbaiah et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Patent ‘582 encompass compositions which are specific to granzyme B and uses thereof.
The difference between the instant claims and that of Patent ‘582 is the use of an aryl ring instead of a piperidine or piperazine ring.
However, Subbaiah et al. teach bioisosteres of the phenyl ring: recent strategic applications in lead optimization and drug design (see title). Furthermore, Subbaiah et al. disclose that the benzene moiety is the most prevalent ring system in marketed drugs, underscoring its historic popularity in drug design either as a pharmacophore or as a scaffold that projects pharmacophoric elements. However, introspective analyses of medicinal chemistry practices at the beginning of the 21st century highlighted the indiscriminate deployment of phenyl rings as an important contributor to the poor physicochemical properties of advanced molecules, which limited their prospects of being developed into effective drugs. This Perspective deliberates on the design and applications of bioisosteric replacements for a phenyl ring that have provided practical solutions to a range of developability problems frequently encountered in lead optimization campaigns. While the effect of phenyl ring replacements on compound properties is contextual in nature, bioisosteric substitution can lead to enhanced potency, solubility, and metabolic stability while reducing lipophilicity, plasma protein binding, phospholipidosis potential, and inhibition of cytochrome P450 enzymes and the hERG channel (see abstract).
It would have been prima facie obvious to provide the granzyme B composition of Patent ‘582 together with an aryl group substituted for a piperidine or piperazine ring adjacent to the chelating group. One of ordinary skill in the art would have been motivated to do so because an aryl ring system is a bioisostere of the piperidine and piperazine ring systems (see title and abstract within Subbaiah et al.). There would have been a reasonable expectation of success given that both references teach the medicinal chemistry exploration of analogues based on a structure-activity-relationship (SAR).
Claims 1-2, 4-7, 9-10, 12-13, 15, 17-19, 21, 23-26, and 29 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claim 1-17, 20-36, and 47-48 of co-pending Application No. 18/737,398 (reference application) in view of Wannamaker et al. (WO01/8330A2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Application ‘398 encompass compounds specific to granzyme B and uses thereof.
The difference between the instant claims and that of Application ‘398 is the use of the terminal alkylated alcohol of the lactone to generate ethers.
However, Wannamaker et al. teach process and intermediates for making substituted aspartic acid acetals (see title). Furthermore, Wannamaker et al. disclose a method for making compounds that are useful as caspase inhibitor prodrugs of formula (I), wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is preferably a P2-P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones (III) and (VIII).
It would have been prima facie obvious to provide the lactone ether derivatives with application ‘398 as suggested by Wannamaker et al. (see title and abstract within Wannamaker et al.). There would have been a reasonable expectation of success in doing so as both Wannamaker et al. and Application ‘398 are comprise a lactone containing an oxygen capped with a hydrogen or a small chain alkyl group.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 9, 23, and 24 are 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.
Claims 9 and 24 have the linker sequence of -D-Glu-b-Ala-b-Ala-Ile-. Furthermore, claims 9 and 24 specifically ascertain the chirality of the terminal lactone moiety within the analogue series. Both these elements in combination were absent from the prior art.
Claim 23 has more than one linker sequence enumerated within the disclosed Markush group. However, the analogues in which the oxoazepinoindoline portion with a lactone moiety and the chelating group comprising a 18F-Al-labelled variant are linked with these various residues are all unique to the prior art.
Motivation is lacking to add any of these claim limitations to the closest reference of Goggi et al.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/ Supervisory Patent Examiner, Art Unit 1615
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