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/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 5/26/26 is acknowledged. The election of the species below is also acknowledged. It is note that variable Z3 is undefined in the elected species, as such it is interpreted that Applicant has at least elected Z1 and Z2 to be pendant group 10 with Q5 as sulfonate.
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Claims 1-33 are pending, of which claims 13-33 are withdrawn as being directed to a non-elected invention. Claim 5 is withdrawn as being directed to a non-elected species. Claims 1-4 and 6-12 encompass the elected invention and species and are examined herein on the merits for patentability.
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.
Claim 4 is 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 phrase "where applicable" in parentheses renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The claim includes the limitation wherein the macrocycle has the following structures:
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; however claim 1 requires that when two of the pendant groups are structures 1, 1’, 2, 3, 8 or 14 or any combination thereof, then the third is not 1, 1’, 2, 3, 8 or 14.
Further, the claim includes the following structures which do not feature a Z3 moiety consistent with claim 1.
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In addition, the claim includes the following structures:
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, however, clam 1 requires that not all the pendant groups are the same.
Further the claim includes the following structures:
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, however claim 1 does not allow for H equivalent to position Z3. As such the claim fails to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The following reference, which contains at least one species directed to a non-elected species as presented below, was found during the search for the elected species. It should not be interrupted that a comprehensive search was performed for all non-elected species.
Claim(s) 1-3 and 7-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Morrow et al. (US 2020/0079806).
Morrow discloses a macrocyclic compound having i) a macrocyclic core comprising at least one heteroatom as a ligand donor and ii) at least one pendant donor as a substituent of the macrocyclic core. A macrocyclic compound may be referred to as a ligand when the macrocyclic compound is coordinated to an iron(III) ion. The macrocyclic core has a ring structure comprising carbon atoms and at least one heteroatom (e.g. N atom, O atom, or S atom). The macrocyclic compound may comprise one or more ancillary pendant groups. The ancillary pendant group (s) may be one or more coordinating ancillary pendant groups and/or one or more non-coordinating ancillary pendant groups (paragraph 0010-11).
The disclosure provides imaging methods using the macrocyclic complexes and compounds. The imaging methods use magnetic resonance imaging methods (MRI). Specifically, the macrocyclic compounds of the present disclosure, which are complexed to Fe(III), can be used as T1 MRI contrast agents. The imaging methods of the present disclosure can be used to image a cell, tissue, organ, vasculature, or a part thereof. The cell, tissue, organ, vasculature can be a part of an individual (paragraph 0015).
Exemplary compounds are shown below:
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Such compounds are within the scope of the instant claims such that Z1 and Z2 correspond to pendant group 1 and R1 is a substituted phenyl.
Additives such as human serum albumin (has) or meglumine may be used to increase solubility and/or increase relaxivity (paragraph 0116).
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) 1-4 and 6 -12 are rejected under 35 U.S.C. 103 as being unpatentable over Morrow et al. (US 2020/0079806) in view of Tallec et al. (Inorg. Chem., 2011, 50, 7943–7945).
Morrow teaches a macrocyclic compound having i) a macrocyclic core comprising at least one heteroatom as a ligand donor and ii) at least one pendant donor as a substituent of the macrocyclic core. A macrocyclic compound may be referred to as a ligand when the macrocyclic compound is coordinated to an iron(III) ion. The macrocyclic core has a ring structure comprising carbon atoms and at least one heteroatom (e.g. N atom, O atom, or S atom). The macrocyclic compound may comprise one or more ancillary pendant groups. The ancillary pendant group (s) may be one or more coordinating ancillary pendant groups and/or one or more non-coordinating ancillary pendant groups (paragraph 0010-11).
The disclosure provides imaging methods using the macrocyclic complexes and compounds. The imaging methods use magnetic resonance imaging methods (MRI). Specifically, the macrocyclic compounds of the present disclosure, which are complexed to Fe(III), can be used as T1 MRI contrast agents. The imaging methods of the present disclosure can be used to image a cell, tissue, organ, vasculature, or a part thereof. The cell, tissue, organ, vasculature can be a part of an individual (paragraph 0015).
In clam 1, a macrocyclic complex is claimed comprising: a macrocyclic core comprising from 9 to 15 atoms, wherein at least one of the atoms in the macrocyclic core is a N atom, at least two carbon atoms separate a heteroatom selected from the group consisting of: N atom, O atom, or S atom, and one or more of the following pendant groups are substituents on the macrocyclic core:
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…, etc.
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,
… and a high-spin Fe(III) cation complexed to the macrocyclic core and/or at least one pendant group substituent of the macrocyclic compound, or a salt, a partial salt, a hydrate, a polymorph, or a stereoisomer thereof, wherein the macrocyclic compound exhibits a redox potential of less than 0 vs. normal hydrogen electrode (NHE) in an aqueous medium at a pH of 6.5-7.5.
The macrocyclic complex of claim 1 includes a macrocyclic core having the following structures:
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, etc.
Including wherein for all structures I-XVI, each of Z1, Z2, Z3 and Z4 where applicable pendant groups are selected independently of each other (claims 1-11).
An exemplary compound may be, for example:
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(claim 12).
As such, one or two Z1 or Z2 may correspond to pendant group 1 of the instant claims, and one or two Z10 of the instant claims (see pendant groups 2, 16 and 17 of Morrow).
With regard to the elected species compound wherein Z1 and Z2 correspond to pendant group 10 of the instant claims, Morrow does not exemplify wherein one or both of Z1 and/or Z2 correspond to pendant group 10 including Q5 as a sulfonate.
Tallec teaches high relaxivity and stability of a hydroxyquinolinate-based tripodal monoaquagadolinium complex for use as a bimodal MRI/Optical imaging agent.
An octadentate ligand based on triazacyclo nonane and 8-hydroxyquinolinate/phenolate binding units leads to very soluble, highly stable lanthanide complexes. The monoaquagadolinium complex shows a high relaxivity as a result of the unusually long rotational correlation (abstract).
Here, we describe the interesting relaxivity, stability and luminescence properties of lanthanide complexes of the octadentate ligand dhqtcn-SO3 3-- containing two hydroxiquinolinate groups and one phenolate group connected by a triazacyclononane core. The triazacyclononane appeared as an attractive ligand scaffold because of its capacity to enhance the solubility and stability of Gd chelates and to yield a fast water exchange rate and a long electronic relaxation time, which are physical properties both favorable to an increase of the relaxivity. The ligand H3dhqtcn-SO3 was synthesized in four steps from commercial 1,4,7-triazacyclononane.
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In summary, the complexes [Ln(dhqtcn-SO3)(H2O)] with their very high thermodynamic stability comparable to that of commercial contrast agents, associated with their kinetic inertness, their high relaxivity under physiological conditions, which further increases significantly and sharply in serum, and their sizable quantum yields are very attractive systems as bimodal probes endowed with high relaxivities and fluorescent properties (page 7945).
It would have been obvious to one of ordinary skill in the art at the time of the invention to provide an iron (III) complex of a triazacyclononane macrocycle having Z1, Z2 and Z3 comprising one or two pendant groups corresponding to pendant group 1 and one or two pendant groups corresponding to pendant group 10, including Q3-5 = H and/or SO3- when the teaching of Morrow is taken in view of Tallec. One would have been motivated to do so, with a reasonable expectation of success, because Morrow teaches that the macrocyclic compounds, based on tacn, may have Z1, Z2 and Z3 pendant groups independently selected from pendant groups 1-19, including
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,
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,
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, etc. such as similar to the TOBA macrocycle. One would have been further motivated to provide a sulfonate group as one of the Q groups on the phenolate pendant group because Tallec teaches
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as a pendant group from a TACN macrocycle as a coordinating ligand for MRI contrast agents having the benefit of high water solubility. See also MPEP 2144.09. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c).
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEAH H SCHLIENTZ whose telephone number is (571)272-9928. The examiner can normally be reached Monday-Friday, 8:30am - 12:30pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL 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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/LHS/
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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