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 .
Drawings
The drawings are objected to because Figures 1 are 2 are exact duplicates of each other. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Please note that changes to the drawings cannot introduce new matter into the disclosure as originally filed.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: the specification as filed lacks antecedent basis for all of the steps recited in claim 10 and parenchymal as an administration route.
Claim Rejections - 35 USC § 112 – Written Description
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 - 13 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. This is a written description rejection.
Each independent claim contains the same chemical formula, a compound known as indocyanine blue or CUR-438 amongst others names, that is broadened by the recitation “or a salt, solvate, hydrate, polymorph or prodrug, thereof”. The written description requirement has not been sufficiently met for the genus prodrugs of the compound whose formula is recited in each of the independent claims.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus. The disclosure of a representative number of species within a claimed genus can be sufficient to satisfy the written description requirement as it is not necessary to disclosed every species within the genus. A description that merely renders a claimed invention obvious may not sufficiently describe the invention for the purposes of the written description requirement of 35 U.S.C. 112 (MPEP 2163 (I)).
No definition as to the scope of the term “prodrugs” or actual examples of prodrugs of the claimed compound are set forth in the specification as filed although there is an incorporation by reference statement to a non-patent literature document at ¶ [0067] of the PGPub of the instant application. But this is not a complete definition and is an improper incorporation by reference as essential subject matter can only be incorporated by reference to a U.S. patent or U.S. patent application publication that does not itself incorporate such essential material by reference. Each claim is also drawn to a method and the compound must convert into the active form to carry out the claimed function when administered. The method of claims 12 and 13 relating to angiography seem particularly problematic as prodrugs given that Frangioni et al. (US 2016/0263249) indicates that the data acquisition for angiography takes places within seconds of administration (¶ [0180]), seemingly requiring conversion of the prodrug to the non-prodrug form in a very short time frame to allow the imaging process to take place. The claims relating to sentinel lymph nodes could use compounds with slower kinetics of conversion to the active form although again the disclosure in lacking as to a written description of such compounds.
Given the lack of disclosure of any species of prodrugs of the claimed compound, there is no disclosure of a representative number of species within the claimed genus of prodrugs of the claimed compounds and therefore the written description requirement is not fully satisfied.
The dependent claims fall therewith.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 5, 9 and 11 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.
Among the claimed routes for administration in each of these claims is “parenchymal administration” and the scope of this administration route is not understood. Parenchyma is “[t]he essential or functional elements of an organ” (see definition from National Cancer Institute, accessed August 10, 2026) which does not clarify how and/or where the contrast agent would be administered in such a fashion. The claims are not requiring that the administered compounds merely come into contact with the parenchyma of an organ but that the administered step is parenchymal administration and does not appear to be an art recognized route such as subdermal or subcutaneous. Please clarify.
Claims 10 and 11 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.
Step (d) recites “the identified sentinel lymph node” (singular) but step (c) references identification of “the sentinel lymph nodes” (plural), rendering it unclear if only one SLN or the more than one SLN identified in step (c) is analyzed. This step also seems to also require removal of at least one sentinel lymph node (SLN) but there is no positively recited active step requiring removal of any tissue or samples from the organism. One possible analysis method is “conventional histopathology” which is not defined in the claims or the specification and convention can change over time such that new methods become conventional and/or methods that were once considered to be conventional are no longer conventional. Therefore the scope of the analysis methods encompassed by step (d) cannot be determined and can change over time, rendering the metes and bounds of this step unclear.
Step (e) recites “determining if the sentinel lymph node removed in the biopsy contain malignant cancer cells” (emphasis added). There is insufficient antecedent basis for the limitation “the biopsy” and there is no recited method step requiring removal of any tissue.
Based on all of the above, the metes and bounds of claim 10 cannot be determined.
The dependent claim falls therewith.
Please clarify.
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 – 9, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Frangioni et al. (US 2016/0263249).
Frangioni et al. discloses near-infrared (NIR) fluorescent biological contrast agents and methods of using (whole document, e.g., abstract). The methods can comprise contacting the biological tissue cells with a compound of the invention; irradiating the cells at a wavelength absorbed by the compound and detecting the signal from the compound, thereby imaging the biological cells (¶¶ [0166] – [0169]). The cells could be normal or tumor cells (¶ [0017]). The examples use in vivo imaging (¶ [0179]) and the subject or patient can be human (¶ [0091]). When injected into the bloodstream, the NIR contrast agent can act as an angiographic agent with the initial seconds after administration providing a map of the circulation in the tissue (¶ [0180]). In this method, the blood is contacted with the contrast agent, the blood vessels and surrounding tissues are irradiated at a wavelength absorbed by the compound and the signal is detected, thereby imaging the distribution and clearance of the fluorophore in the tissue (¶¶ [0180] – [0184]). Another possible use is as sentinel lymph node agents that are injected in and around a tumor and quickly flow to the first lymph node that drains a tumor (¶¶ [0359] – [0363]). Amongst the possible targets are sentinel lymph nodes (¶ [0018]). Figures 5 and 6 depict SLN detection using two different compounds at 800 nm and 700 nm respectively. A variety of means of administration are disclosed including intravenously (¶ [0177]), subcutaneous (¶ [0154]) and when injected subdermally, may enter the lymphatic channels and flow to a lymph node (¶ [0020]). Compound MHI85 shown on p 50 is the same compound as the instant claims. Different compounds of the invention can absorb at different wavelengths in the NIR region such as 660 - 720 nm or 760 – 820 nm (¶ [0122]).
There are no explicit example in which MHI85 is administered to an organism and signal detection or imaging carried out using irradiation purpose.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to administer MHI85 to a subject, who can be a human, for purposes such as the sentinel lymph node identification to or blood vessels for angiography, followed by irradiation of the tissue and detecting of the signal form the contrast agent. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Frangioni et al. discloses compounds including MHI85 are NIR contrast agents that can be administered for a variety of uses, including the compounds are administered and can come into contact with sentinel lymph nodes as required by claims 1 - 9. Depending on the particular application, one of ordinary skill in the art can select different contrast agents depending on the desired use. For each compound selected, one of ordinary skill in the art can determine the optimal irradiation wavelength. The detected signal can be interpreted in different ways as reflected in the preambles of claims 1 and 6 although the method steps themselves are the same. These various outcomes of imaging, which can be used to provide a map when viewed in the appropriate manner and to detect cancer cells are all disclosed by Frangioni et al. As to claims 12 and 13, Frangioni et al. discloses that the contrast agent should contact the blood which will result in contact of the blood vessels and/or coronary lumens of the subject with the compound as in the NIR angiography method disclosed by Frangioni et al.
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Frangioni et al. as applied to claims 1 – 9, 12 and 13 above, further in view of Noguchi et al. (Br J Surgery, 2002).
Frangioni et al. is discussed above.
While SLN analysis is disclosed, analyzing an identified SLN and determining if the SLNs removed in the biopsy contain malignant cancer cells is not disclosed.
Noguchi discloses SLN biopsy has been developed to assess accurately the axillary node status without removal of most of the axillary contents, with a tumor-negative SLN virtually excluding lymphatic involvement in the entire regional lymphatic basin (p 21, col 1, ¶ 1). Histological examination of axillary lymph nodes is discussed beginning on p 26, col 2, ¶ 4 and can detect micrometastases (p 27, col 1, ¶ 1), which reads on the step of determining if the SLN removed in the biopsy contain malignant cells. The use of intraoperative examination using frozen section cytology is discussed beginning on p 27, col 2, ¶ 2.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to once identified using a contrast agent such as MHI58, to remove a SLN node and analyze that SLN for malignant cells and determining if the SLN contains malignant cancer cells using methods such as those disclosed by Noguchi. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because SLN analysis is known to those of ordinary skill in the art and once identified using a contrast agent, can be further analyzed to determine if malignant cells are present using methods such as those discussed by Noguchi.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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