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 .
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 1-8 and 14-18, drawn to a conjugate comprising an immunoglobulin single variable domain conjugated to one or more detectable labels and pharmaceutical composition comprising the conjugate as recited in claim 1.
Group II, claim(s) 9-13, 19 and 20, drawn to a method for in vivo medical imaging for prognostic, diagnostic and/or interventional purposes as recited in claim 9.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Group I lack unity of invention because even though the inventions of these groups require the technical feature of conjugate comprising an immunoglobulin single variable domain conjugated to one or more detectable labels, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Schnermann et al. (WO 2019/161159) discloses heptamethine cyanine conjugates or conjugate precursor are highly resistant to aggregation when conjugated to a targeting agent, e.g., a biomolecule such as an antibody (immunoglobulin). The conjugate has a structure of formula:
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(page 1-3 and claim 1).
As a result, no special technical feature exists among the different groups because the invention in Groups I and II fail to make a contribution over the prior art and are therefore not “special”
During a telephone conversation with John Dimaino on 06/22/2026 a provisional election was made without traverse to prosecute the invention of Group I, claims 1-8, and 14-18. Affirmation of this election must be made by applicant in replying to this Office action. Claims 9-13, 19 and 20 withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/29/2024 was noted and the submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 03/29/2024. These drawings are acknowledged.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-8, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Stijlemans Benoit et al. (WO 2014037419) in view of Schnermann et al. (WO 2019161159) and Bradley D. Smith et al. (Angew Chem Int Ed, 59, 12154-12161, 2020) . Stijlemans discloses pharmaceutical compositions, comprising immunoglobulin single variable domains directed against CD74 for the treatment of inflammatory diseases, including cancer, as well as for detecting, monitoring and/or diagnosing a particular disease in the field of inflammation (abstract). The immunoglobulin single variable domain of the invention inhibits MIF and D-DT from binding to CD74 and comprises an amino acid sequence that comprises 4 framework regions (F) and 3 complementarity determining regions (CDR) according to the following formula (1): F 1-CD 1-F 2-CD 2-F 3-CD 3-F 4 (1); or any suitable fragment thereof (page 3 line 25+). In one embodiment, the immunoglobulin single variable domain comprises a polypeptide or may be fused to a moiety, either directly or through a linker. The moiety may be a detectable label or a therapeutically active agent (page 4 Line 23-25). Stijlemans discloses that the immunoglobulin single variable domains within the scope of the invention may be further modified and/or may comprise (or can be further fused to) other moieties. For example, such a modification may involve the introduction (e.g. by covalent linking or in another suitable manner) of one or more functional groups, residues or moieties into or onto the immunoglobulin single variable domain, and in particular of one or more functional groups, residues or moieties that confer one or more desired properties or functionalities to the immunoglobulin single variable domain. Such functional groups may for example be linked directly (for example covalently) to immunoglobulin single variable domain, or optionally via a suitable linker or spacer. Yet another modification may comprise the introduction of one or more detectable labels or other signal-generating groups or moieties, depending on the intended use of the labeled immunoglobulin single variable domain. Thus, according to a preferred embodiment, the immunoglobulin single variable domain is coupled or fused to a detectable label, either directly or through a linker. Suitable labels include, but are not limited to, fluorescent labels, (such as I Dye800, VivoTag800, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, and fluorescamine and fluorescent metals such as Eu or others metals from the lanthanide series), phosphorescent labels, chemiluminescent labels or bioluminescent labels, radio-isotopes (such as technetium 99m (99mTc), iodium 123 (123l), zirconium 89 (89Zr), iodium 125 (125l), indium 111 (111ln), fluor 18 (18F), copper 64 (64Cu), gallium 67 (67Ga), gallium 68 (68Ga)), metal, metals chelates or metallic cations or other metals or metallic cations that are particularly suited for use in in vivo, in vitro or in situ diagnosis and imaging (page 22 line 15-25). Additional disclosure includes that the immunoglobulin single variable domain specifically recognizes or specifically binds to a desirable antigen, in particular CD74, that is present in a homogeneous mixture of different antigens and does not necessarily imply high affinity. The specific binding interaction will discriminate between desirable and undesirable antigens in a sample, more than about 10 to 100-fold, or more than about 1000-10,000-fold.
Stijlemans fails to disclose fluorescent moiety having a structure chosen from formula I or formula II:
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.
Schnermann discloses conjugates and conjugate precursors comprising a heptamethine cyanine fluorophore and a targeting agent or a functional group suitable for forming a conjugate with a targeting agent. The conjugate or conjugate precursors have a chemical structure of formula I or a stereoisomer thereof:
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(abstract and page 13 line 30+) wherein Rc is a targeting agent-containing group, the targeting agent capable of recognizing and binding to the target; subsequently irradiating the biological sample with a quantity of light having a selected wavelength and selected intensity to induce fluorescence of the conjugate; and detecting fluorescence of the irradiated biological sample, wherein fluorescence indicates presence of the target in the biological sample. In some embodiments, the targeting agent is an antibody (page 4 Line 4-10). In some examples, the targeting agent is capable of recognizing and binding to cells of the tumor, irradiating the biological sample comprises irradiating the target area of the subject, and detecting fluorescence indicates presence of tumor cells in the target area, and the method further includes excising fluorescent tumor cells from the target area (Page 4 Line 15-20 ). In certain embodiments, the conjugates also exhibit exceptionally bright in vivo signals when compared to conventional heptamethine cyanines, including persulfonated heptamethine cyanines, such as the commercially available IRDye.sup.®-800CW fluorophore (page line ). Advantageously heptamine cyanine conjugates are highly resistant to aggregation when conjugated to a targeting agent, e.g., a biomolecule such as an antibody (immunoglobulin)or receptor ligand. In certain embodiments, the conjugates also exhibit exceptionally bright in vivo signals when compared to conventional heptamethine cyanines.
Smith discloses synthesis of shielded and charge-balanced heptamethine cyanine dye s775z along with two bioconjugates (Scheme 1).
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. Smith discloses that standard amide bond conjugation chemistry was used to react the NHS ester of s775z with a free amine on the cyclic peptide targeting unit, cRGDfK, s775z-IgG and create the homologous fluorescent peptide probe s775z-RGD (scheme 1). Amide bond formation was also used to attach multiple copies of s775z to an antibody. Additional disclosure includes that compared to the benchmark heptamethine cycnine dyes, shielded s775z and its bioconjugates exhibit an unsurpassed combination of photophysical, physiochemical and biodistribution properties that greatly enhance bioimaging performance. Additional bioconjugation studies showed that multiple copies of shielded s775z can be attached to an antibody to produce a densely labeled conjugate without any stacking of appended fluorochromes. Next generation versions of densely labeled s775z-antibodies can likely be used as very bright, fluorescent probes for deployment at microdoses in various diagnostics or clinical imaging procedures.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate fluorescent moieties of formula I into Stijlemans’ composition. The person of ordinary skill in the art would have been motivated to make those modifications because Schnermann teaches that antibody conjugates of FNIR-Tag exhibited superior tumor uptake and brightness when compared to a similarly labeled IRDye.sup.®-800CW conjugate in an in vivo imaging study in mice bearing EGFR+ tumors and additionally conjugates show reduced liver uptake compared to conventional heptamethine cyanine conjugates, such as IRDye.sup.®-800CW-based conjugates (page 19 line 1-8) and reasonably would have expected success because advantageously heptamine cyanine conjugates are highly resistant to aggregation when conjugated to a targeting agent, e.g., a biomolecule such as an antibody (immunoglobulin) or receptor ligand and also exhibit exceptionally bright in vivo signals when compared to conventional heptamethine cyanines.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate fluorescent moieties of formula II into Stijlemans’ composition. The person of ordinary skill in the art would have been motivated to make those modifications because Smith teaches that compared to the benchmark heptamethine cycnine dyes, shielded s775z and its bioconjugates exhibit an unsurpassed combination of photophysical, physiochemical and biodistribution properties that greatly enhance bioimaging performance (page 12159) and reasonably would have expected success because next generation versions of densely labeled s775z-antibodies can likely be used as very bright, fluorescent probes for deployment at microdoses in various diagnostics or clinical imaging procedures.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGADISHWAR RAO SAMALA whose telephone number is (571)272-9927. The examiner can normally be reached Monday-Friday 9am-6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Hartley G Michael 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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/J.R.S/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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