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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 11 April 2023, have been entered in full. Claims 1-11 and 17 are canceled. Claims 13, 14, 16 and 20 are amended. New claim 21 is entered. Claims 12-16, 18-21, drawn to a method of therapeutic ALCAM/CD166 protein modulation in a subject comprising administering a recombinant human fusion protein ILT3Fc, are under examination.
Information Disclosure Statement
The information disclosure statement(s)(IDS) (filed 4/11/23, 11/10/23 and 10/9/24) were received. They have been placed in the application file and the information referred to therein has been considered as to the merits.
It is noted that some of the references fail to comply with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. MPEP 609.05 [R-3] states that information disclosure statements will be reviewed for compliance with the requirements of 37 CFR 1.97 and 37 CFR 1.98 as discussed in MPEP 609.04(a) and MPEP 609.04(b). The references will be lined through and not considered by the Examiner.
References: The references should include in the following order:
the name of the author, title of the article, name of the item (i.e. book, magazine, Journal, symposium, catalog, etc.), the volume-issue number, the pages, and date.
The following references not considered by the Examiner for the following reasons: This is regarding the references cited on the IDS submitted 11/10/2023.
The author is incorrectly listed at the end of the reference, the title of the reference is missing, the name of the journal is missing and/or the page numbers of the reference is missing.
Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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.
Claims 12-16, 18-21 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.
(1) Claim 12 is indefinite because it recites the acronyms "ALCAM” and “ILT3” which have not been defined in the claims. The presence of an undefined acronym renders a claim indefinite. Acronyms should be defined upon their first use in a claim.
Claims 13-16 and 18-21 are included in this rejection insofar as they depend from claim 12 and do not resolve the issue discussed above.
(2) Claim 14 is indefinite because of the recitations, “wherein the administering does not comprise additional blood-brain barrier technology” and “direct central nervous system (CNS) dose administration”. These limitations are not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree. Therefore, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 15 and 16 are included in this rejection insofar as they depend from claim 14 and do not resolve the issue discussed above.
(3) Claims 20 and 21 are indefinite because of the recitation “ultrasensitive assay configured to..”. The claims recite the function of the assay, but not teach the actual assay that is required to measure the level of ALCAM/CD166. The metes and bounds of these claims cannot be determined.
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 12, 14 and 16 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification teaches a method of therapeutic ALCAM/CD166 target modulation in a subject can comprise administering to the subject a sufficient, and brain-penetrating intravenous dose of substantially purified recombinant human fusion protein ILT3Fc, or alternatively or additionally, direct CNS administration of a significantly reduced dose of said ILT3Fc, wherein the reduced dose further achieves both CNS and peripheral systemic exposure, and wherein the administered dose further reduces the level of soluble shed ALCAM/CD166 measured in a peripheral blood sample compared to a reference value or reference group, and thereby indicating the therapeutic modulation (para 0017). The specification teaches that said therapeutic modulation is for the treatment of Alzheimer's Disease and/or neurological complications of COVID-19 (para 0300).
The Examples teach administering recombinant human Fc fusion protein ILT3Fc (i2RX-001) to a pre-clinical mouse model (para 0207). The Examples teach a reduction of ALCAM in blood (para 0246).
The instant claims are not enabled for the following reasons:
The specification fails to teach administering a recombinant human fusion protein ILT3Fc or functional fragment thereof to treat Alzheimer’s disease or neurological complication of COVID-19.
The specification does not teach that the pre-clinical mouse model is an art recognized animal model for Alzheimer’s disease or an art recognized animal model for neurological complications of COVID-19. Thus, it could not be predicted that the animal model data presented in the specification would be correlative with in vivo treatment for Alzheimer’s disease or neurological complication of COVID-19.
See wherein Justice et al. teach, “it seems an obvious point, but the model used should be appropriate for the question being addressed. An ideal disease model accurately mimics the human condition, genetically, experimentally and/or physically”. Justice et al. teach that in one example, data from human blunt-trauma patients were analyzed together with data from a mouse inbreed strain that had been exsanguinated. Justice et al. teach, “Losing a large amount of blood does not equate to blunt trauma, and so this could be perceived as comparing apples to oranges” (page 101, 2nd column 2nd full paragraph). Justice et al. teach that in a different study, a mouse model was reported to display the key motor symptoms seen in humans with amyotrophic lateral sclerosis (ALS). On the basis of this, the model was used in preclinical trial studies and promising drugs candidates were tested in clinical trials; however the drugs ultimately failed in humans. It was shown that the particular mouse is a poor genetic and phenotypic model of human conditions. Justice et al. state, “This example illustrates how relevance to the human disease being studied, supported by strong data to validate the use of the model is crucial for clinical translation” (page 102, left column, 1st full paragraph)(Justice et al. Using the mouse to model human disease: increasing validity and reproducibility, Disease, Models & Mechanisms 9:101-103, 2016).
Goodarzi et al. teach that one of the most common age-related neurodegenerative disorders is Alzheimer’s disease (AD). Goodarzi et al. teach that animal studies can improve our understanding of biological mechanisms of diseases. Goodarzi et al. teach that to gain suitable outcomes, it is important to check the appropriate validation of animal models. Goodarzi et al. teach that animal models which are applied for AD can be divided into three groups including genetic, natural, and interventional models. The animal models have the following specific features of stability, repeatability and having the behavioral characteristics and generally validity of different AD features (page 144). Goodarzi et al. teach genetic models are preferred to better understand the biology of fundamental features of disease. Genetic models of AD are designed based-on the targeted genes which contribute to develop Familial Alzheimer’s disease (FAD) and sporadic forms. Goodarzi et al. teach AD forms have several differences with each other and some of their treatments are not the same; the animal model of one form is not suitable for treatment studies on another form (page 145). Goodarzi et al. teach aged animals can possibly be employed as natural models of dementia and memory loss disorders because the loss of memory is the initial and prevalent sign of aging. Different animals including dogs, cats, polar bears, sheep, goats, and some non-human primates can develop AD-associated neuro-pathological properties spontaneously. Goodarzi et al. teach that there are different interventional AD models based on intracranial injections of chemical materials or the induction of lesions in particular brain regions. Some of chemically-induced models are Ab peptide-induced and scopolamine-induced amnesia models. In general, chemically-induced models can cause dementia in animals through neurotransmitter pathways and neuronal blocking. Lesion-induced models can help understand the mechanisms of cholinergic innervations in the therapy of cognitive dysfunctions. Lesions can be produced through electrolytical and surgical methods, intracerebroventricular and intraparenchymal microinjections of neurotoxic materials including N-methyl-D-aspartic, ibotenic, and the cholinotoxin AF64 (page 145-146). Most importantly, Goodarzi et al. teach animal models should be validated in accordance with three major aspects. Predictive validity (function in the test predicts function in the situation being modeled), face validity (phenomenological relations), and construct validity (theoretic basis). The predictive validity implies the similarity of the association between the triggering factors and the appearance of the disease, and further the medicinal agents and the cure of disease. The face validity of a model determines the similarity of observations in the animal model and the human. Construct validity is used to measure accuracy. This type of validity focus on homological similarity between animals and humans (page 146)(Goodarzi et al. Development and validation of Alzheimer’s Disease Animal Model for the Purpose of Regenerative Medicine. Cell Tissue Bank 20:141–151, 2019).
The references discussed above evidences the fact that the animal model used should be appropriate for the question(s) being addressed.
It cannot be said that the specification provides the necessary guidance for treating Alzheimer’s disease or neurological complications of COVID-19. The specification provides insufficient guidance with regard to these issues and provides no working examples which would provide guidance to one skilled in the art to predict the efficacy of the claimed methods with a reasonable expectation of success. It would have been unpredictable what affects a recombinant human fusion protein ILT3Fc or functional fragment thereof would have when administered to a patient. For the above reasons, undue experimentation would be required to practice the claimed invention.
Due to the inherent unpredictability and the large quantity of experimentation to demonstrate that all forms of Alzheimer’s disease and/or neurological symptoms of COVID-19 can be treated in a patient after administering human fusion protein ILT3Fc or a functional fragment thereof; the lack of direction/guidance presented in the specification regarding same; the absence of working examples directed to same; the complex nature of the invention; and the state of the art which establishes that use of proper animal models to study treatment, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 12, 14 and 15 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Suciu-Foca et al. (US 2009/0274685; published 05 November 2009).
The Examiner notes that the instant claims do not recite a method of treating a particular condition or disease. The claims read on administering a human fusion protein ILT3Fc or functional fragment thereof to a subject.
Suciu-Foca et al. teach administering an ILT3Fc fusion protein to a subject (abstract). Suciu-Foca et al. teach wherein the subject is human (para 0075). Suciu-Foca et al. teach that the fusion protein comprises ILT3 and the Fc portion of IgG (para 0066). Suciu-Foca et al. teach that the ILT3Fc fusion protein is a human fusion protein (paras 0061, 0065, 0080, 0083)(applies to claim 12). Administering a human fusion protein ILT3Fc to a subject would inherently reduce a level of soluble shed ALCAM/CD166 protein in blood of the subject (applies to claim 12). Suciu-Foca et al. teach “administering" shall mean delivering in a manner which is effected or performed using any of the various methods and delivery systems known to those skilled in the art. Suciu-Foca et al. teach administering can be performed, for example, topically, intravenously, pericardially, orally, via implant, transmucosally, transdermally, intradermally, intramuscularly, subcutaneously, intraperitoneally, intrathecally, intralymphatically, intralesionally, or epidurally (para 0055)(applies to claim 14). Suciu-Foca et al. teach intravenously administering a single dose of ILT3Fc fusion protein in an effective amount of 20 mg/kg (paras 0125 and 0126)(applies to claim 15).
Claims 12-15, 18 and 19 are rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Suciu-Foca et al. (Reference submitted by Applicant; US 2018/0207269; published 26 July 2018).
The Examiner notes that the instant claims do not recite a method of treating a particular condition or disease. The claims read on administering a human fusion protein ILT3Fc or functional fragment thereof to a subject.
Suciu-Foca et al. teach it has now been discovered that activated lymphocyte cell adhesion molecule (ALCAM) also known as CD166 is the ligand of the innate immune receptor ILT3 that is expressed by DC and monocytes. Suciu-Foca et al. teach it has been further discovered that the specific binding of ILT3 to its ligand ALCAM/CD166 on the surface of CD166-expressing cancer cells, arrested cancer cell growth and initiated apoptosis. Suciu-Foca et al. teach methods for treating CD166-expressing cancers by administering ILT3Fc to subjects (abstract and para 0003)(applies to claim 12). Suciu-Foca et al. teach that the fusion protein comprises ILT3 and the Fc portion of IgG. Suciu-Foca et al. teach that the ILT3Fc fusion protein is a human fusion protein (paras 0036, 0038, 0039, 0041)(applies to claim 12). Administering a human fusion protein ILT3Fc to a subject would inherently reduce a level of soluble shed ALCAM/CD166 protein in blood of the subject (applies to claim 12). Suciu-Foca et al. teach wherein the subject is human (para 0045). Suciu-Foca et al. teach the term “administering” as used herein, means a manner which is affected or performed using any of the various methods and delivery systems known to those skilled in the art. Administering can be performed, for example, topically, intravenously, pericardially, orally, via implant, transmucosally, transdermally, intramuscularly, subcutaneously, intraperitoneally, intrathecally, intralymphatically, intralesionally, or epidurally (para 0033)(applies to claim 14). Suciu-Foca et al. teach intravenously administering a single dose of ILT3Fc fusion protein in an effective amount of 20 mg/kg (paras 0075)(applies to claim 15).
Suciu-Foca et al. teach ALCAM/CD166 expression has been found in several malignancies, which include melanoma, prostate, breast, colorectal, lung, pancreas, hepatocellular, and head and neck carcinoma (para 0058). Suciu-Foca et al. teach that in order to test if ALCAM/CD166 is the ligand of ILT3Fc, anti-CD166 PE and ILT3Fc-FITC double staining of PMA or CD3 plus CD28 antibody-triggered CD3+T cells from healthy individuals was performed. ILT3Fc bound to CD166-positive cells, indicating that they were co-expressed. When the cells were triggered in the presence of ILT3Fc, the ILT3Fc binding was inhibited. Suciu-Foca et al. teach ALCAM/CD166 expression by the same ILT3Fc-treated cells, was also inhibited indicating a positive correlation between ILT3Fc binding and ALCAM/CD166 expression (para 0123).
Suciu-Foca et al. teach a method of determining if a subject afflicted with cancer has a CD166-expressing cancer that would be susceptible to treatment methods taught herein. The method comprises obtaining a biological sample from a subject afflicted with cancer, wherein the biological sample comprises cancer cells; contacting the cancer cells in the biological sample with an anti-CD166 antibody or a CD166-binding fragment thereof; determining whether the cancer cells bind to the anti-CD166 antibody, or CD166-binding fragment thereof; and if the cancer cells bind to the anti-CD166 antibody, or CD166-binding fragment thereof, then treating the cancer by administering to the subject a therapeutically effective amount of an ILT3Fc fusion protein (para 0073)(applies to claim 13). Suciu-Foca et al. teach a method comprising administering to a subject having a CD166-expressing cancer a therapeutically effective amount of an ILT3Fc thereby treating the cancer and reducing the proliferation of the CD166-expressing cancer cells compared to respective pretreatment levels (claims)(applies to claim 13). Suciu-Foca et al. teach biological samples are collected from a person’s body and include blood samples (para 0035)(applies to claim 18). Suciu-Foca et al. teach the binding between the anti-CD166 antibody, or CD166-binding fragment and the epitope on ALCAM/CD166 can be determined by using ELISA (paras 0102 and 0144)(applies to claim 19). Suciu-Foca et al. teach treatment with ILT3Fc significantly inhibited the tumor proliferation as shown by the tumor burden change in the FIG. 12. Suciu-Foca et al. teach that the formed solid tumor volume is significantly smaller than that of in the control treated group as shown in FIG. 13. Suciu-Foca et al. teach the ILT3Fc treatment remarkably increased the survival percentage as shown in the FIG. 14 (paras 0017-0019 and 0152).
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.
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.
Claims 12-15, 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Suciu-Foca et al. (US 2018/0207269; published 26 July 2018) in view of Rusling, James F. (Nanomaterials-based electrochemical immunosensors for proteins. ABSTRACT. Chemical record, New York, N.Y., Vol. 12, No. 1, pp. 164-76. Feb 2012. Electronic Publication Date: Jan 30, 2012).
The Examiner notes that the instant claims do not recite a method of treating a particular condition or disease. The claims read on administering a human fusion protein ILT3Fc or functional fragment thereof to a subject.
Suciu-Foca et al. teach it has now been discovered that activated lymphocyte cell adhesion molecule (ALCAM) also known as CD166 is the ligand of the innate immune receptor ILT3 that is expressed by DC and monocytes. Suciu-Foca et al. teach it has been further discovered that the specific binding of ILT3 to its ligand ALCAM/CD166 on the surface of CD166-expressing cancer cells, arrested cancer cell growth and initiated apoptosis. Suciu-Foca et al. teach methods for treating CD166-expressing cancers by administering ILT3Fc to subjects (abstract and para 0003)(applies to claim 12). Suciu-Foca et al. teach that the fusion protein comprises ILT3 and the Fc portion of IgG. Suciu-Foca et al. teach that the ILT3Fc fusion protein is a human fusion protein (paras 0036, 0038, 0039, 0041)(applies to claim 12). Administering a human fusion protein ILT3Fc to a subject would inherently reduce a level of soluble shed ALCAM/CD166 protein in blood of the subject (applies to claim 12). Suciu-Foca et al. teach wherein the subject is human (para 0045). Suciu-Foca et al. teach the term “administering” as used herein, means a manner which is affected or performed using any of the various methods and delivery systems known to those skilled in the art. Administering can be performed, for example, topically, intravenously, pericardially, orally, via implant, transmucosally, transdermally, intramuscularly, subcutaneously, intraperitoneally, intrathecally, intralymphatically, intralesionally, or epidurally (para 0033)(applies to claim 14). Suciu-Foca et al. teach intravenously administering a single dose of ILT3Fc fusion protein in an effective amount of 20 mg/kg (paras 0075)(applies to claim 15). Suciu-Foca et al. teach ALCAM/CD166 expression has been found in several malignancies, which include melanoma, prostate, breast, colorectal, lung, pancreas, hepatocellular, and head and neck carcinoma (para 0058). Suciu-Foca et al. teach that in order to test if ALCAM/CD166 is the ligand of ILT3Fc, anti-CD166 PE and ILT3Fc-FITC double staining of PMA or CD3 plus CD28 antibody-triggered CD3+T cells from healthy individuals was performed. ILT3Fc bound to CD166-positive cells, indicating that they were co-expressed. When the cells were triggered in the presence of ILT3Fc, the ILT3Fc binding was inhibited. Suciu-Foca et al. teach ALCAM/CD166 expression by the same ILT3Fc-treated cells, was also inhibited indicating a positive correlation between ILT3Fc binding and ALCAM/CD166 expression (para 0123). Suciu-Foca et al. teach a method of determining if a subject afflicted with cancer has a CD166-expressing cancer that would be susceptible to treatment methods taught herein. The method comprises obtaining a biological sample from a subject afflicted with cancer, wherein the biological sample comprises cancer cells; contacting the cancer cells in the biological sample with an anti-CD166 antibody or a CD166-binding fragment thereof; determining whether the cancer cells bind to the anti-CD166 antibody, or CD166-binding fragment thereof; and if the cancer cells bind to the anti-CD166 antibody, or CD166-binding fragment thereof, then treating the cancer by administering to the subject a therapeutically effective amount of an ILT3Fc fusion protein (para 0073)(applies to claim 13). Suciu-Foca et al. teach a method comprising administering to a subject having a CD166-expressing cancer a therapeutically effective amount of an ILT3Fc thereby treating the cancer and reducing the proliferation of the CD166-expressing cancer cells compared to respective pretreatment levels (claims)(applies to claim 13). Suciu-Foca et al. teach biological samples are collected from a person’s body and include blood samples (para 0035)(applies to claim 18). Suciu-Foca et al. teach the binding between the anti-CD166 antibody, or CD166-binding fragment and the epitope on ALCAM/CD166 can be determined by using ELISA (paras 0102 and 0144)(applies to claim 19). Suciu-Foca et al. teach treatment with ILT3Fc significantly inhibited the tumor proliferation as shown by the tumor burden change in the FIG. 12. Suciu-Foca et al. teach that the formed solid tumor volume is significantly smaller than that of in the control treated group as shown in FIG. 13. Suciu-Foca et al. teach the ILT3Fc treatment remarkably increased the survival percentage as shown in the FIG. 14 (paras 0017-0019 and 0152).
Suciu-Foca et al. do not teach measuring the level of ALCAM/CD166 protein by using an ultrasensitive assay that can detect ALCAM/CD166 protein levels below a level of 1 picogram/ml or below a level of 100 femtogram/ml.
Rusling teaches ultrasensitive protein immunosensors that are achieved by combining nanostructured electrodes with particles labeled with up to 1/2 million enzymes that can detect down to as little as 1 femtogram(fg)/mL(-1) protein in diluted serum (applies to claims 20 and 21). Rusling teaches that the most mature multiple protein detection system is a microfluidic device with eight sensors coated with 5-nm gold nanoparticles that uses off-line protein detection with heavily labeled magnetic particles. Rusling teaches that this approach has led to reliable sub picogram(pg)/mL(-1) detection limits for multiple proteins and provides excellent correlation with referee ELISA methods (applies to claim 20). Rusling teaches that the assay is currently being used for validation of panels of biomarkers for oral and prostate cancer.
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a method of comparing reduced ALCAM/CD166 protein levels in a blood sample from a subject that was administered ILT3Fc with prior ALCAM/CD166 protein levels from the subject, as taught by Suciu-Foca et al., by including ultrasensitive protein immunosensors, as taught by Rusling. One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success because Rusling teaches that the ultrasensitive protein immunosensors can detect as little as 1 femtogram(fg)/mL(-1) protein in diluted serum and provides excellent correlation with referee ELISA methods.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REGINA M DEBERRY whose telephone number is (571)272-0882. The examiner can normally be reached M-F 9:00-6:30 pm (alt Fri).
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/R.M.D/Examiner, Art Unit 1647 11/6/2025
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647