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 . Claims included in the prosecution are claims 12-24.
Applicants' arguments, filed 11/12/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
1. Claims 12-14, 17, 19, 20 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US 2013/0272958, Oct. 17, 2013) (hereinafter Zhang) (IDS reference) in view of Hernot et al. (Latest developments in molecular traces for fluorescence image-guided cancer surgery, July 2019) (hereinafter Hernot), as evidenced by ThermoFisher (Alexa Fluor 680 Dye, 2025).
Zhang discloses anti-CEACAM6 antibodies and fragments thereof, and uses thereof (¶ [0009]). The antibody or fragment thereof is linked to a diagnostic agent (¶ [0021]). Suitable diagnostic agents include a near infrared fluorochrome or dye (¶ [0023]), such as Alexa680 (¶ [0083]). The antibody or fragment thereof may be linked to the diagnostic agent using any method known in the art (¶ [0089]). An antibody fragment may include any suitable antigen-binding antibody fragment known in the art. For example, an antibody fragment may include, but is not limited to, scFv and F(ab’)2 (¶ [0060]). The antibody or fragment thereof is specific for carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6). While CEACAM6 has been observed in normal human tissue, its expression is elevated in many solid tumors such as breast (¶ [0064]). The antibody or fragment thereof linked to a diagnostic agent, also referred to as a molecular imagining agent, may be used to perform diagnostic imaging. The imagining technique may include whole body imaging for diagnostic purposes or local imaging at specific sites, such as but not limited to sites of tumor growth, in a quantitative manner to assess the progression of disease or host response to a treatment regimen (¶ [0084]). An in vitro method of detecting tumors comprises administering to a subject the antibody or fragment thereof linked to a diagnostic agent and detecting the binding of the antibody or fragment thereof (¶ [0090]-[0092]). The antibodies are injected (i.e., systemic administration) (¶ [0165]). The detection of localized antibody/molecular imaging agent accumulation indicates the presence and location of a tumor in the subject (¶ [0093]).
Zhang differs from the instant claims insofar as not disclosing wherein the molecular imaging agent is used for performing surgical removal of a breast tumor.
However, Hernot discloses in Figure 1, principle of intraoperative molecular near-infrared (NIR) fluorescence imaging. The bottom of Figure 1 shows implementation of fluorescence guidance during open and laparoscopic surgery. After intravenous injection of a tracer, a tumor or other tissue of interest can be visualized with a specialized NIF camera, thereby guiding a surgeon in real-time during resection. Immediately after resection, the specimen(s) can be imaged on a back table (a table in the operating room equipped to analyze tissue sample) with a fluorescence camera and microscope. The pathologist can thus rapidly check resection margins on the presence of fluorescence and provide rapid feedback to the surgeon (Figure 1).
Zhang discloses uses of the molecular imaging agent. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have used the molecular imaging agent Zhang in intraoperative molecular near-infrared (NIR) fluorescence imaging to remove a tumor since using fluorescence guidance to resect tumors is another known and effective use of molecular imaging agents as taught by Hernot. One of ordinary skill in the art would have removed a breast tumor since Zhang discloses wherein the antibody or fragment thereof of the molecular imagining agent is specific for CEACAM6 and CEACAM6 expression is elevated in many solid tumors such as breast.
In regards to instant claim 13 reciting assaying the tumor using the imaging agent to determine the possibility of surgical removal after step i and prior to step ii, as discussed above, Zhang discloses detecting the presence and location of a tumor in the subject after administering the molecular imaging agent.
In regards to instant claim 14 reciting monitoring the progress of surgical removal, Hernot discloses wherein after resection, the specimen(s) can be imaged on a back table to check resection margins and provide rapid feedback to the surgeon.
In regards to instant claim 22 reciting wherein the imagining agent is detectable using real-time molecular fluorescence imagining, as noted by the instant specification on page 16, dyes that emit fluorescent light are detectable using real-time molecular fluorescence imaging. As evidenced by ThermoFisher, Alexa Fluor 680 is a near-infrared fluorescent dye. As such, since the molecular imaging agent of Zhang comprises Alexa680, the molecular imaging agent of Zhang is detectable using real-time molecular fluorescence imaging.
In regards to instant claim 24 reciting marginal breast cancer tissue, Hernot discloses that in intraoperative molecular near-infrared (NIR) fluorescence imaging to remove a tumor, the pathologist rapidly checks resection margins on the presence of fluorescence and provide rapid feedback to the surgeon. Thus, it would have been obvious that intraoperative molecular near-infrared (NIR) fluorescence imaging to remove a tumor comprises removing marginal breast cancer tissue.
2. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US 2013/0272958, Oct. 17, 2013) (hereinafter Zhang) (IDS reference) in view of Hernot et al. (Latest developments in molecular traces for fluorescence image-guided cancer surgery, July 2019) (hereinafter Hernot), and further in view of Hansen et al. (US 2011/0064653, Mar. 17, 2011) (hereinafter Hansen).
The teachings of Zhang and Hernot are discussed above. Zhang and Hernot do not teach wherein the molecular imaging agent comprises a radiolabel.
However, Hansen discloses humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof (abstract). The Class I anti-CEA antibody or fragment thereof is conjugated to at least one diagnostic and/or therapeutic agent to form an immunoconjugate (claim 13). Suitable therapeutic agents include a radionuclide (claim 15).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have additionally linked a radionuclide to the antibody or fragment thereof of Zhang motivated by the desire to additionally deliver a therapeutic agent as taught by Hansen. One of ordinary skill would have had a reasonable expectation of success since an antibody or fragment thereof may comprise a diagnostic agent and a therapeutic agent as taught by Hansen.
3. Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US 2013/0272958, Oct. 17, 2013) (hereinafter Zhang) (IDS reference) in view of Hernot et al. (Latest developments in molecular traces for fluorescence image-guided cancer surgery, July 2019) (hereinafter Hernot), and further in view of Smith et al. (Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system, Jun. 9, 2018) (hereinafter Smith).
The teachings of Zhang and Hernot are discussed above. Zhang and Hernot do not teach wherein the method is performed following lumpectomy.
However, Smith discloses wherein obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. Smith assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System with and without intravenous LUM015m a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. It was found that the LUM imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins (abstract).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have performed the claimed method following lumpectomy since following lumpectomy there may be residual tumors as taught by Smith.
4. Claims 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (US 2013/0272958, Oct. 17, 2013) (hereinafter Zhang) (IDS reference) in view of Hernot et al. (Latest developments in molecular traces for fluorescence image-guided cancer surgery, July 2019) (hereinafter Hernot), and further in view of Biel et al. (US 2019/0282696, Sep. 19, 2019) (hereinafter Biel) (IDS reference).
The teachings of Zhang and Hernot are discussed above. Zhang and Hernot do not teach wherein the dye is IRdye800 (claimed structure of instant claim 18) or wherein the antibody or fragment thereof is linked to the diagnostic agent via an NHS-ester linkage.
However, Biel discloses conjugates for use in photoimmunotherapy, such as photoimmunotherapy induced by activation of a phthalocyanine dye conjugated to a targeting molecule that binds to a protein on a cell, for example, an IR700-antibody conjugate. The phthalocyanine-dye conjugate can be activated by irradiation with near-infrared light. The conjugates may be used for treatment of diseases and conditions, including tumors or cancers (abstract). The dye can be conjugated to the antibody using the NHS ester of IR700 (¶ [0260]). The conjugate further contains a second fluorescent dye (¶ [0101]). Suitable second dyes include IRDye 800 (¶ [0102]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Zhang discloses wherein the diagnostic agent may be a near infrared fluorescent dye. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated IRDye 800 as the diagnostic agent since it is a known and effective near infrared fluorescent dye as taught by Biel.
It would have been prima facie obvious to one of ordinary skill in the art to have the antibody or fragment thereof and IRDye 800 linkage be via an NHS ester linkage since Zhang discloses wherein the linkage may be any method known in the art and NHS ester linkage is a known and effective method for linking antibodies with IR dyes as taught by Biel.
Response to Arguments
Applicant argues that based on the teachings of Zhang, a person would not have a reasonable expectation of success that use of an anti-CEACAM6 antibody would specifically label only breast cancer tissue and not non-cancerous breast tissue alike.
The Examiner does not find Applicant’s argument to be persuasive. Zhang discloses in paragraph [0003] wherein expression of CEACAM6 protein has been reported in a variety of normal human tissues (Buchegger et al, 1984) including granulocytes; however, CEACAM6 expression is elevated in many solid tumors such as breast, pancreatic, ovarian, lung and colon cancer (Blumenthal et al, 2007). Thus, Zhang discloses wherein expression of CEACAM6 protein has been reported in a variety of normal human tissues but not ALL normal human tissues. Also, granulocytes are formed in bone marrow. Thus, there is no indication in the prior art that one of ordinary skill in the art would have expected non-cancerous breast tissue to have expression of CEACAM6 protein, such that use of an anti-CEACAM6 antibody for specifically labeling only breast cancer tissue and not non-cancerous breast tissue is unexpected. Furthermore, because Zhang specifically discloses wherein CEACAM6 expression is elevated in breast tumors and it was known in the art to use imaging agents when removing a tumor as taught by Hernot, it would have been obvious to one of ordinary skill in the art to have used the CEACAM6 specific imaging agent of Zhang for removing a breast tumor. Applicant has not shown wherein other known imaging agents with elevated expression in breast tumor would have expression in non-cancerous breast tissue thus making use of the claimed anti-CEACAM6 imaging agent for removing a breast tumor unexpected.
Conclusion
Claims 12-24 are rejected.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TRACY LIU/Primary Examiner, Art Unit 1614