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 .
Receipt is acknowledged of Applicant’s Request for Continued Examination and Amendment filed on 12/09/2025; and IDS filed on 08/11/2025.
Claims 16, 29, 32 have been amended.
Claim 35 has been added.
Claims 16-35 are pending in the instant application.
Claims 22-26 are withdrawn from consideration.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/09/2025 has been entered.
Double Patenting
The nonstatutory 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 nonstatutory 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 nonstatutory 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 nonstatutory 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 16-21, 27-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 9,645,138. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent recites a method for detecting a molecule of interest in at least one target tissue, the method comprising the steps of: administering the molecule of interest to at least one animal; selecting at least one control compound for detection, wherein the properties of the at least one control compound in binding or incorporating in the at least one target tissue are known; sampling at least one section of the target tissue from the at least one animal at a given time post administration of the molecule of interest; and detecting the distribution on the surface of the at least one target tissue section of: i) the molecule of interest, and ii) the at least one control compound (see claim 1), wherein the at least one control compound comprises a positive control compound and a negative control compound (see claim 2), wherein the detection of the distribution of the molecule of interest and the at least one control compound comprises an imaging technique (see claim 6), wherein the detection of the distribution of the molecule of interest and the at least one control compound comprises mass spectrometry molecular imaging (see claim 7), wherein specificity of the molecule of interest for the target tissue comprises detecting the distribution of said molecule in the target tissue and detecting the distribution of said molecule in at least one non-target tissue (see claim 10), the method further comprising the steps of: sampling a first target tissue section of the at least one target tissue of the at least one animal, at a first given time (t1) post administration of the molecule of interest; sampling a second target tissue section of the at least one target tissue of the at least one animal, at a second given time (t2) post administration of the molecule of interest; and detecting the distribution of the molecule of interest in the target tissue sections taken at t1 and t2 (see claim 11), wherein the molecule of interest is a candidate molecule, a therapeutic potential molecule or a phytosanitary potential molecule or one of its metabolites (see claim 12). A computer-readable data medium comprising computer-executable instructions suited to enable a computer system to execute the comparison of the distribution of the molecule of interest with the distribution of at least one control compound according to the method of claim 1 (see claim 14). Note, “target” in target tissues is a target site and would read on molecular marker.
The difference between instant application and the patented claims is that the patent claims include additional limitations. Thus, the invention of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”, and, therefore, the application claims are not patentably distinct from the claims of the patent and are rejected on the ground of nonstatutory obviousness-type double patenting. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
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.
Claim(s) 16-21, 27, 29-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HAMM et al (US 2015/0377862).
HAMM teaches a method for evaluating if a molecule of interest (see abstract), such as a new drug candidate (see [0003]), binds at least one target tissue (see abstract) to screen biomarkers (see [0010] and marker well-known properties for the target tissue (see [0011]), which reads on a method for ex-vivo or in-vitro evaluation of an effect of first molecule of interest on at least one molecular marker in a dosed biological sample, comprised of:
-visualizing and comparing the distribution of the molecule of interest and of at least one control compound within the target tissue or on the target tissue surface of at least one animal that has previously received the molecule of interest and/or the control compound (see abstract), which reads on selecting a dosed biological sample, which has been previously exposed to said first molecule of interest;
-mass spectrometry imaging experiment on tissue sections comprising the target tissue and a peripheral tissue, non-targeted (see [0029] and Figs2-3, 6-8), which reads on detecting the presence of the first molecule of interest in the dosed biological sample with a molecular imaging method and obtaining a molecular map of the dosed biological sample for the first molecule of interest;
-the method of the invention is performed using mass spectrometry imaging (MSI), widely used to study central nervous system from its first development. The continuous improvement of spatial resolutions available during MSI experiment gives the access to fine histological and biological structure as the BBB can be (see [0058]). The method of the invention can be used to assess this competition directly within tissue sections, using MSI or any molecular imaging technique (see [0061]), which reads on spatially segmenting the molecular map of the dosed biological sample as a function of spectral information to obtain a segmentation map of the first molecule of interest in the dosed biological sample;
-the similarity and/or dissimilarity of the distributions of each molecule of interest compared to the control compounds, which reads on second ROI, distributions allows appreciating spatial similarities of the distribution for each molecule within the target tissue. The tissue penetration ratio for the molecules of interest is evaluated by comparing intensity maps of said molecules of interest and control compounds related to the amount of control compounds in said target tissue (see [0029]), which reads on selecting a first region of interest (ROI) from the segmentation map, said first ROI having a first intensity for the at least one molecule of interest and measuring the intensity or quantity of at least one molecular marker in said first ROI and comparing the intensity or quantity of at least one molecular marker in the first ROI with the intensity or quantity of at least one molecular marker in a second ROI, said second ROI being selected from the dosed biological sample or from another biological sample, “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and reads on wherein the second ROI is selected from the segmentation map of the dosed biological sample, said second ROI having a second intensity for the first molecule of interest and an effect of the first molecule of interest is “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI”.
Note, the limitation of “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI” appear to be a mental step.
The method of the invention can be used to evaluate the distribution of all molecules measurable using imaging techniques, especially a protein, a peptide, a lipid, an antibody, a nucleic acid (see [0013]). It is also possible to perform antibody labeling (coupled or not with a tag), on tissue sections, or to use fluorescence labeled molecules or radioactivity to allow the detection of the molecule of interest and control compounds (see [0070]). The target tissue studied can be a whole organ, a specific region within an organ, a biological barrier, etc. For example, the target tissue is an organ such as a lung, an eye, a liver, a kidney, a heart, etc., or a biological barrier such as the blood-brain barrier, or a specific region of an organ, such as a tumor tissue, especially a cerebral tumor tissue, etc. (see [0014]).
Additional disclosures include: screen candidate molecules and evaluate their therapeutics or diagnostics potentials (see [0002]), which reads on evaluation of an effect of a first molecule of interest; mass spectrometry imaging (MSI) (see [0011]); possible in some case to perform in-vivo analysis on the living whole animal (see [0068); MRI and PET imaging (see [0074]); MALDI (see [0072]); proteomics, lipidomics or pharmaceutics research in order to screen candidate molecules and evaluate their therapeutics or diagnostics potential (see [0002]); the methodology of adsorption of a molecule on tissue using the example of receptor occupancy process. By this way, it is possible to measure the occupancy efficiency of the receptor by the drug (agonist), which could be the antibody, administered to the animal compared with an antagonist molecule (see [0148]-[0149]), which would be the anti-antibody; the skilled person knows, from existing liquid or solid matrices, which one can be used depending on studied molecules and/or target tissue (see [0072]), wherein tissue cells (see [0065]) in a liquid would read on cell suspension, such as using LESA (Liquid Extraction Surface Analysis) (see [0075]) or ESI (liquid extraction on tissue) (see [0111]); extraction of molecule of interest from tissue (see [0070]).
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.
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.
Claim(s) 16-21, 27-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over HAMM et al (US 2015/0377862) in view of KLINGHOFFER et al (US 2014/0170146).
As discussed above, HAMM teaches a method for evaluating if a molecule of interest (see abstract), such as a new drug candidate (see [0003] and [0010]), binds at least one target tissue (see abstract) to screen biomarkers (see [0010]) and marker well-known properties for the target tissue (see [0011]), which reads on a method for ex-vivo or in-vitro evaluation of an effect of first molecule of interest on at least one molecular marker in a dosed biological sample, comprised of:
-visualizing and comparing the distribution of the molecule of interest and of at least one control compound within the target tissue or on the target tissue surface of at least one animal that has previously received the molecule of interest and/or the control compound (see abstract), which reads on selecting a dosed biological sample, which has been previously exposed to said first molecule of interest;
-mass spectrometry imaging experiment on tissue sections comprising the target tissue and a peripheral tissue, non-targeted (see [0029] and Figs2-3, 6-8), which reads on detecting the presence of the first molecule of interest in the dosed biological sample with a molecular imaging method and obtaining a molecular map of the dosed biological sample for the first molecule of interest;
-the method of the invention is performed using mass spectrometry imaging (MSI), widely used to study central nervous system from its first development. The continuous improvement of spatial resolutions available during MSI experiment gives the access to fine histological and biological structure as the BBB can be (see [0058]). The method of the invention can be used to assess this competition directly within tissue sections, using MSI or any molecular imaging technique (see [0061]), which reads on spatially segmenting the molecular map of the dosed biological sample as a function of spectral information to obtain a segmentation map of the first molecule of interest in the dosed biological sample;
-the similarity and/or dissimilarity of the distributions of each molecule of interest compared to the control compounds, which reads on second ROI, distributions allows appreciating spatial similarities of the distribution for each molecule within the target tissue. The tissue penetration ratio for the molecules of interest is evaluated by comparing intensity maps of said molecules of interest and control compounds related to the amount of control compounds in said target tissue (see [0029]), which reads on selecting a first region of interest (ROI) from the segmentation map, said first ROI having a first intensity for the at least one molecule of interest and measuring the intensity or quantity of at least one molecular marker in said first ROI and comparing the intensity or quantity of at least one molecular marker in the first ROI with the intensity or quantity of at least one molecular marker in a second ROI, said second ROI being selected from the dosed biological sample or from another biological sample, “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and reads on wherein the second ROI is selected from the segmentation map of the dosed biological sample, said second ROI having a second intensity for the first molecule of interest and an effect of the first molecule of interest is “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI”.
Note, the limitation of “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI” appear to be a mental step.
The method of the invention can be used to evaluate the distribution of all molecules measurable using imaging techniques, especially a protein, a peptide, a lipid, an antibody, a nucleic acid (see [0013]). It is also possible to perform antibody labeling (coupled or not with a tag), on tissue sections, or to use fluorescence labeled molecules or radioactivity to allow the detection of the molecule of interest and control compounds (see [0070]). The target tissue studied can be a whole organ, a specific region within an organ, a biological barrier, etc. For example, the target tissue is an organ such as a lung, an eye, a liver, a kidney, a heart, etc., or a biological barrier such as the blood-brain barrier, or a specific region of an organ, such as a tumor tissue, especially a cerebral tumor tissue, etc. (see [0014]).
Additional disclosures include: screen candidate molecules and evaluate their therapeutics or diagnostics potentials (see [0002]), which reads on evaluation of an effect of a first molecule of interest; mass spectrometry imaging (MSI) (see [0011]); possible in some case to perform in-vivo analysis on the living whole animal (see [0068); MRI and PET imaging (see [0074]); MALDI (see [0072]); proteomics, lipidomics or pharmaceutics research in order to screen candidate molecules and evaluate their therapeutics or diagnostics potential (see [0002]); the methodology of adsorption of a molecule on tissue using the example of receptor occupancy process. By this way, it is possible to measure the occupancy efficiency of the receptor by the drug (agonist), which could be the antibody, administered to the animal compared with an antagonist molecule (see [0148]-[0149]), which would be the anti-antibody; the skilled person knows, from existing liquid or solid matrices, which one can be used depending on studied molecules and/or target tissue (see [0072]), wherein tissue cells (see [0065]) in a liquid would read on cell suspension, such as using LESA (Liquid Extraction Surface Analysis) (see [0075]) or ESI (liquid extraction on tissue) (see [0111]); extraction of molecule of interest from tissue (see [0070]).
HAMM does not teach using laser capture microdissection to extract the ROI from the biological sample.
KLINGHOFFER teaches the prior art had known of individual cells or cluster of cells are isolated by laser-capture microdissection and tissue sample may be obtained by biopsy (see [0189]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate laser capture microdissection to extract the ROI from the biological sample. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because laser-capture microdissection, biopsy, and the other tissue extraction discussed in HAMM are functional equivalents of tissue extractions well-known in the prior art.
Response to Arguments
Applicant argues that Hamm et al. do not disclose, nor suggest, to evaluate if the presence of the molecule of interest in the target tissue has an impact on the control compound. Indeed, the purpose of Hamm et al. is to evaluate the tissue specificity of the molecule of interest by comparing the targeting, i.e. binding of the molecule of interest with the known targeting, i.e., binding of the control compound. The positive control compound, whose specificities for the target tissue are known, is used as a reference with respect to tissue specificities. The molecular intensity of the positive control compound within the target tissue is compared to the molecular intensity of the molecule of interest within said tissue. If the molecular intensities are the same, then the molecule of interest is a good candidate molecule because it specifically binds to the target tissue. No interaction between both molecules is evaluated nor expected in Hamm et al. Hamm et al. thus disclose the comparison of the molecular information of two different molecules, a reference/control compound and a molecule of interest, within a same tissue sample. In contrast, the claimed invention involves the comparison of the molecular information of a same molecule, a molecular marker, within two different regions of interest (ROIs) of a same tissue sample of a different tissue sample. More particularly, the claimed invention requires one to measure and compare the molecular information (intensity or quantity) of a molecular marker within two RO Is, with respect to the molecular information of a molecule of interest within said two ROIs, in order to determine if the presence of the molecule of interest in the first ROI has an impact on the molecular marker in said first ROI. If the presence of the molecule of interest in the first ROI leads to a reduction of the intensity (or quantity) of the molecular marker in said first ROI, as compared to the molecular information of the molecular marker in the second ROI, it means that the presence of the molecule of interest has an impact on the molecular marker such as, e.g., the molecule of interest is able to cleave the molecular marker. Hamm et al. do not disclose or suggest such a method, e.g., a method that is able to determine if a molecule of interest has an impact on a molecular marker ( or control compound). Both methods (Hamm et al. and the present method) may be complementary and may be performed successively. For instance, (1) a candidate molecule is screened by the method of Hamm et al., as specifically targeting the kidney: this is determined by comparing the distribution of said candidate molecule with the distribution of a control molecule already known as specifically targeting the kidneys. Then, (2) the candidate molecule is administered to a kidney sample ( dosed kidney sample) and the molecular information of a marker molecule within the dosed kidney sample is compared to the molecular information of said marker molecule within a kidney sample deprived of the candidate molecule. The differences between both molecular information are directly correlated to the presence/absence of the candidate molecule. If the molecular information in the first kidney sample is different from the molecular information in the second kidney sample, then the candidate molecule has an impact on the marker molecule. Hamm et al. do not teach nor suggest such a method, in particular such a step of comparing the molecular information of the molecular marker within both tissue samples. Hamm et al. teach how to compare the molecular information of the molecular marker with the molecular information of the candidate molecule within a same tissue sample.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, HAMM teaches the similarity and/or dissimilarity of the distributions of each molecule of interest compared to the control compounds, which reads on second ROI, distributions allows appreciating spatial similarities of the distribution for each molecule within the target tissue. The tissue penetration ratio for the molecules of interest is evaluated by comparing intensity maps of said molecules of interest and control compounds related to the amount of control compounds in said target tissue (see [0029]), which reads on selecting a first region of interest (ROI) from the segmentation map, said first ROI having a first intensity for the at least one molecule of interest and measuring the intensity or quantity of at least one molecular marker in said first ROI and comparing the intensity or quantity of at least one molecular marker in the first ROI with the intensity or quantity of at least one molecular marker in a second ROI, said second ROI being selected from the dosed biological sample or from another biological sample, “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and reads on wherein the second ROI is selected from the segmentation map of the dosed biological sample, said second ROI having a second intensity for the first molecule of interest and an effect of the first molecule of interest is “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI”. Note, the limitation of “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI” appear to be a mental step.
Applicant argues that the Office Action's allegation that Hamm et al.' s control compound reads on Applicant's molecular marker in a second ROI, Applicant notes that claim 16 recites measuring the intensity or quantity of at least one molecular marker in said first ROI; and comparing the intensity or quantity of said at least one molecular marker in the first ROI with the intensity or quantity of said at least one molecular marker in a second ROI. That means, if the Office Action's allegation were correct, Hamm et al.' s control compound would read on both, the molecular marker in the first and second ROI. However. Hamm et al. disclose regions of interest as target and non-target regions (see Fig. 1, Tissue and Tissue l; Fig. 2, Cortex and Medulla; paragraphs 10, 23, 28, 29, 30, 31, 32, 39, 40, 45, 81, 114-119, 135-137, 140, 141, and 148 referring to target tissue and non-target tissue; paragraphs 80, 91, 94, 95, 96, 144, and 145 referring to target issue and adjacent, non-target tissue; and paragraph 97 and 127 referring to target tissue and outside the target tissue or center area of the tissue section and peripheral area of the tissue section). Further, when Hamm et al. disclose distribution of a molecule of interest into at least two sections of target tissue, Hamm et al. refer to sampling of two sections that were previously obtained by sampling at different times (tl) and t2) (Hamm et al., page 2, paragraph 26). Moreover, Hamm et al. disclose target tissue and non-target or adjacent non-target tissue as being defined by the presence of Hamm et al.'s positive and negative control markers, respectively. Therefore, if Hamm et al.' s control compound read on Applicant's molecular marker in a second ROI, and consequently on Applicant's molecular marker in a first ROI-since they are the same molecule marker as recited in claim 16-Hamm et al.' s control compound would be present in both RO Is, which according to Hamm et al.' s regions of interest as target and non-target or adjacent non-target tissues would render Hamm et al.' s method inoperable for evaluating tissue targeting of a molecule of interest. Thus, the Office Action's allegation is inconsistent with Hamm et al.' s teachings. In addition, Hamm et al. do not teach determining the intensity or quantity of a same molecular marker in different regions of interest.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, HAMM teaches the similarity and/or dissimilarity of the distributions of each molecule of interest compared to the control compounds, which reads on second ROI, distributions allows appreciating spatial similarities of the distribution for each molecule within the target tissue. The tissue penetration ratio for the molecules of interest is evaluated by comparing intensity maps of said molecules of interest and control compounds related to the amount of control compounds in said target tissue (see [0029]). Note, the limitation of “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI” appear to be a mental step.
Applicant argues that the Examiner refers to [0003] and [001 O] as teaching a method to evaluate the effects of a molecule of interest (e.g., a candidate molecule) on another molecule (e.g., a molecular marker) in a target tissue and disregards Applicant's argument that Hamm et al. do not disclose a method to evaluate the effect of the candidate molecule on the control compound already present in the target tissue as unpersuasive (see page 16, 4th paragraph, and page 17, second paragraph of the Office Action). However, the teaching of said paragraphs does not lead to, nor even suggest, the claimed method. As indicated in paragraph [0003]: [0003] Developing a drug, from early candidate molecule discovering up to the placing on the market of the product, is a long and costly process, involving significant human and equipment investment. Notably, clinical trials which involved human test, could take several years. The aim of these trials is to ensure the efficiency of the drug, highlight potential side effects and evaluate the safety concerns of the therapeutics. Thus, paragraph [0003] generally refers to trials that are performed once a candidate molecule is discovered to determine if it may for sure be a relevant drug ( e.g., evaluation of the side effects, safety, etc.). This paragraph does not teach anything. Paragraph [0010] (reproduced below) teaches that the method of Hamm et al. may be used to screen molecules with potential therapeutic effect (i.e., selection of the candidates molecules that specifically bind to the target tissue). [0010] Thus, the method of the invention can be used to achieve a fast and reliable screening of molecules with a potential therapeutic effect and be able to select the one that may enter in a drug formulation to treat a given disease depending of a target tissue. The method of the invention can also be applied to verify potential side effects from the molecule of interest, for example on untargeted tissue(s)
where the molecule can be bound. As well, the method of the invention can be used in proteomics, for example to screen biomarkers to select reliable diagnostic molecule(s) of a given pathology. Here, the Office Action combines two independent and unrelated paragraphs (i.e., [0003] and [0010]) and picks some words from a sentence of paragraph [0003] to combine them with other words of the abstract and additional words from a paragraph [0010]. By doing so, the Examiner creates a totally new and unsupported sentence. Applicant submits that this is improper. The last sentence of [0010] teaches that the candidate molecule to be screened may be a biomarker selected because it is a reliable diagnostic molecule for a given pathology, nothing more. In fact, the whole teaching of Hamm et al. focuses on the determination of the capacity of a candidate molecule (e.g., biomarker, diagnostic molecule, etc.) to specifically bind or not bind to a tissue of interest. Even considering the newly created sentence and associated alleged teachings put forward by the Office Action, which Applicant contests, this fails to reproduce the claimed invention. Indeed, the alleged teaching of Hamm et al., as created by the Office Action, is not a method wherein the molecular information of a molecular marker within a first and a second ROI are compared, with respect to the presence of a molecule of interest ( candidate molecule), to determine if the molecule of interest has an impact on the molecular marker. Neither does the whole disclosure of Hamm et al. The Office Action further refers to [0029] of Hamm et al., relating to the data of Fig. 2. Again, this paragraph and Fig. 2 fail to describe a method that evaluates the impact of a first molecule on a second molecule. Paragraph [0029] and Fig. 2 only teach to compare the distribution of Ml, M2, M3 with the distribution of (M+) and (M-): "The similarity and/or dissimilarity of the distributions of each molecules of interest compared to the control compounds distributions allows appreciating spatial similarities of the distribution for each molecule within the target tissue." The distributions of all the molecules are compared with each other within a same sample. There is no evaluation of a potential impact of one molecule on the distribution of another molecule by comparison of different tissue samples or different regions of interest of a same tissue sample. Paragraph [0029] further states: "The tissue penetration ratio for the molecule of interest is evaluated by comparing intensity maps of said molecules of interest and control compounds related to the amount of control compounds in said target tissue." Thus, once the presence of the molecule of interest in the target tissue is confirmed (by evaluation of the distribution), the amount of molecule of interest in the target tissue is determined by comparison of the intensity map of the molecule of interest with the intensity map of the control compound (whose quantity in the target tissue is known) within the same tissue sample. Again, there is no evaluation of a potential impact of one molecule on the distribution of another molecule by comparison of different tissue samples or different regions of interest of a same tissue sample. According to Hamm et al., the control compound is used as a standard molecule: its known localization in the target tissue (i.e., distribution/specificity and intensity/amount) is used as a reference to evaluate the localization of a candidate molecule in said target tissue. Therefore, the claimed method is novel over the teachings of Hamm et al.
The Examiner finds this argument unpersuasive, because [0011]]) explicitly teaches “the method according to the invention proposes to use, as a marker, a molecule with well-known properties for the target tissue and to compare its distribution in said tissue with the distribution of the candidate molecule”. Additionally, the limitation of “to determine if the presence of the first molecule of interest has an effect on the molecular marker” and “determined when the intensity or quantity of said at least one molecular marker is different in the first ROI and the second ROI” appear to be a mental step.
Applicant argues that the claims of the' 138 patent do not recite measuring the intensity or quantity of at least one molecular marker in a first ROI and comparing the intensity or quantity of said at least one molecular marker in said first ROI with the intensity or quantity of said at least one molecular marker in a second ROI. Instead, the' 138 claims recite sampling at least one target tissue at a given time and detecting the distribution of the molecule of interest and the at least one control compound ( claim 1 ); detecting the distribution of said molecule of interest in the target tissue and detecting the distribution of said molecule (the molecule of interest) in at least one non-target tissue ( claim 10); and sampling a first and a second target tissue and detecting the distribution of the molecule of interest in the target tissue sections taken at a given time tl and t2 ( claim 11 ). None of the claims of the '138 patent recite measuring the intensity or quantity of the control compound in a first and second region of interest as required by the current claims.
The Examiner finds this argument unpersuasive, because the patent recites “detecting the distribution”, which reads on “measuring the intensity or quantity”. Additionally, claim 14 recites “comparison of the distribution of the molecule of interest with the distribution of at least one control”.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618
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