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 .
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.
Withdrawn Objections/Rejections
The objections to the specification are withdrawn in response to the amendments.
The rejections of the claims under 112a written description are withdrawn in response to the amendments.
The 102 rejections are withdrawn in response to the amendments. However, new grounds of rejection are set forth below.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/EP2020/066292, filed 06/12/2020. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. EP19382496.8, filed on 06/13/2019 in Europe.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of the Claims
Claims 1-9, 11-14, 17, 19 and 24-26 are pending; claims 1, 5, 12, 14, 19 and 26 are amended; claims 10, 15-16, 18 and 20-23 are cancelled; claims 1-9, 11, 19 and 25-26 are withdrawn. Claims 12-14, 17 and 24 are examined below.
New Rejections
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.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. Current Pharmaceutical Biotechnology, 2015, 16, 716-723 DOI: 10.2174/1389201016666150505121713 (“Yu”) in view of Micromod: "Micro-Tools in Life Science Modular Designed Particles" January 1, 2017; XP093093499; retrieved from the internet. https://donar.messe.de/exhibitor/labvolution/2017/R260918/micromod-product-overview- eng-490167.pdf -Cite No. C1 of IDS filed 2/8/2024 and Yap Malaysian J Path01 1994; 16(1): 49 - 56.
Regarding claim 12, Yu suggests a method for detecting and/or characterizing pathogens present in an isolated test sample (“simultaneous detection of pathogenic bacteria using agglutination test based on colored silica nanoparticles” Title, “The pullorum and S. gallinarum and E. sakazakii in the infected food sample were detected” Abstract), the method comprising: (a) contacting in a vessel comprising a bottom and a wall, and in a buffered aqueous liquid solution the sample where pathogens are to be detected, with coloured particles as defined in claim 1 (“The IgG-red-SiNps were finally washed three times with phosphate buffered saline (PBS) buffer (pH 7.3) and resuspended in 5mL of the same buffer. Blue-SiNps were coated with antibodies against S. pullorum and S. gallinarum in the same manner, denoted as IgG-blue-SiNps…All agglutination tests were performed by the same procedure: On a glass microscope slide, two circles with a diameter of about 1.5 cm were marked with an oil pen. 20 µL of test solution was aliquoted onto one concave circular of glass microscope slide, and 20 µL of the IgG-colored-SiNps suspension was added with a pipette” page 717 col. 2 paras. 3-4). Note that a concave circular slide would inherently provide a vessel comprising a bottom and a wall. Regarding claim 1, Yu teaches a coloured spherical or substantially spherical particle, comprising: a core with a surface (Figure 1); and a pathogen ligand, wherein the pathogen ligand is immobilized on the surface of the core (“Before immobilizing antibodies onto the nanoparticles, the surfaces of the colored-SiNps were chemically modified by APTE and succinic anhydride… Red-SiNps were coated with antibodies against E. sakazaki by chemical bond… Blue-SiNps were coated with antibodies against S. pullorum and S. gallinarum in the same manner” page 717 col. 2 paras. 2-3); wherein at least the surface is coloured, and wherein the core of the particle is made of a silica-based material (Title). Yu further suggests (b) allowing the coloured particles to sediment by passive gravitational force for a time from 1 to 20 minutes after the contacting step (“The test solution and IgG-colored-SiNps suspension were smeared with the toothpick and gently rocked back and forth for 1-3 min” page 717 col. 2 para. 4); and
(c) determining a sedimentation pattern of the coloured particles (Figures 2-6 and 8), wherein coloured particle sedimentation on the bottom or walls of the vessel indicates lack of pathogen in the sample, while the lack or absence of sedimentation is indicative of agglutinated particles, which means that interaction between the pathogen ligand on the surface of the coloured particles and the pathogen in the sample has taken place and that the pathogen has been recognized by pathogen ligand (“A test was positive if colored agglutination was observed in the test circle while no agglutination was found in the control circle. A test was negative if no agglutination was found in the test circle” page 717 col. 2 para. 4), and the assay takes place in the buffered aqueous liquid solution (page 717 col. 2 paras. 2-4, “0.5 mL of 1×109 CFU/mL E. sakazakii and 24.5 mL PBS (pH7.3) buffer. The other one was diluted to 25 mL with PBS (pH 7.3)… 0.5 mL 1×109 CFU/mL S. pullorum and S. gallinarum was added into one of the chicken liver sample and diluted to 25 mL with PBS (pH 7.3)… the other one was diluted to 25 mL with PBS (pH7.3)” page 718 col. 1 para. 1, “Mixture of IgG-red-SiNps and IgG-blue-SiNps and mixture of the two corresponding bacteria were all dropped onto concave circular glass slides” page 719 col. 2 para. 5). Note that although Yu fails to use the language “sedimentation on the bottom or walls of the vessel” , the teachings of “dropped onto concave circular glass slides” and Figures 2 and 4-8 of Yu inherently provides sedimentation on the bottom or walls of the vessel. Furthermore, given that the results of Yu appear identical to the data disclosed in the instant specification, the sedimentation on the bottom or walls of the vessel is inherently present in the vessel of Yu.
Yu fails to teach the particle core having a material mass density from 1.5 to 2.5 g/cc and a diameter from 1 to 10 μm; and wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl, and wherein step (a) is performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core.
Micromod teaches “sicastar®-red, sicastar®-blue and sicastar®-black” (page 17). Micromod further teaches the particle core having a material mass density from 1.5 to 2.5 g/cc and a diameter from 1 to 10 μm (“colored silica particles are available in the size range of 100 nm to 1 μm as monodisperse and nonporous particles with a density of 2.0 g/cm3, and have broader size distributions in the area of the porous silica particles with adjusted diameters between 3 and 20 microns and a density of 1.8 g/cm3” page 17 para. 2). Micromod further teaches wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl (“The coloured particles are available with … NH 2 groups on the particle surface” page 17 para. 3). Micromod further teaches that “[t]he colored silica particles are produced by hydrolysis of orthosilicates and related compounds. They are extremely stable in organic solvents and buffers. No toxic effects come from the covalently bound dyes” (page 17 para. 3). Micromod further teaches the company’s contact information (“micromod Partikeltechnologie GmbH, Fnedrich-Barnewitz-Straf3e 4, 18119 Rostock, Germany Tel.: +49 381/54 34 56 1 D, Fax: +49 381/54 34 56 20, e-mail: inlo@micromod.de, Internet: www.micromod.de” page 17 footnote).
Yap teaches the “[d]evelopment of a slide latex agglutination test for rotavirus antigen detection” (Title). Yap further teaches the method comprising contacting a particle with a test sample, allowing the particles to sediment and determining the sedimentation pattern (“Slide latex agglutination test A 10µl volume of sample was placed on a microscope slide and mixed with an equal volume of latex reagent… The slide was then rocked gently and the appearance of agglutination observed with the unaided eye against a dark background” page 2 col. 1 para. 4 and col. 2 para. 1). Yap further suggests wherein step (a) is performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core (“[i]n this study, raising the pH of the admixture to 9.5 preserved the stability of the antibody-coated particles in the presence of high ionic strength without affecting the performance of the test. An additional advantage of maintaining a high pH is that antibodies are fully charged” page 55 col. 1 para. 3). Yap further suggests that performing step (a) at a pH that is higher than an average isoelectric point of the particle “causes the arms of the antibodies to be completely extended, thus allowing more effective contact and interaction with antigens” (page 55 col. 1 para. 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Yu to rely on the particle core having a material mass density from 1.5 to 2.5 g/cc, a diameter from 1 to 10 μm and wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl, taught by Micromod because Micromod suggests that this enables the particles to be "extremely stable in organic solvents and buffers" (page 17 para. 3). A person having ordinary skill in the art would have had a reasonable expectation of success because Micromod teaches the production method of the particles and teaches their contact information.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Yu in view of Micromod to rely on wherein step (a) being performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core taught by Yap because Yap teaches that this enables the particles to have more effective contact and interaction with antigens. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu and Yap teach methods of detecting and/or characterizing pathogens present in an isolated test sample comprising: contacting a particle with a test sample, allowing the particles to sediment and determining the sedimentation pattern.
Claims 13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of Micromod and Yap, as applied to claim 12 above, and further in view of Lu et al. (WO 2007018843 A2) (“Lu”).
Regarding claim 13, Yu in view of Micromod and Yap teach the method of claim 12 as discussed above.
Yu in view of Micromod and Yap fail to teach wherein in step (a) a competitive ligand of the pathogen is added, competing for the interaction of the pathogen ligand on the surface of the core of the coloured particles with the pathogen in the sample.
Lu “provides method and compositions for determining the presence and amount of an influenza virus in a sample including high risk strains of Influenza A” (Abstract). Lu further teaches that “"Capture agent/analyte complex" is a complex that results from the specific binding of a capture agent, e.g. a PDZ domain fusion protein, with an analyte, e.g. an influenza viral protein having a PL…where one of the binding members is immobilized on a solid phase” (paragraph 72). Lu further teaches that “[r]epresentative solid phases include … latex beads” (paragraph 79). Lu suggests wherein in step (a) a competitive ligand of the pathogen is added, competing for the interaction of the pathogen ligand on the surface of the core of the particles with the pathogen in the sample (“In yet other embodiments, PL proteins and PL peptides are conjugated with signal generating compounds (PL-SGC) and used in competitive ligand inhibition assays, i.e., where the presence of a viral PL competes the binding of one or more PL-SGC to a PDZ…For tests that generally identify influenza A, a mixture of PDZ proteins and antibodies can be used. For these tests, the PDZ protein may include one of the above in admixture with others that recognize other pathogen-specific or influenza A specific PL motifs” paragraph 174).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yu in view of Micromod and Yap to rely on the wherein in step (a) a competitive ligand of the pathogen is added, competing for the interaction of the pathogen ligand on the surface of the core of the particles with the pathogen in the sample taught by Lu because Lu suggests that this enables identification of influenza A virus and Yu in view of Micromod and Yap are concerned with detecting pathogens. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu in view of Micromod and Yap and Lu teach methods for detecting and/or characterizing pathogens present in an isolated test sample using particles with immobilized ligands.
Regarding claim 17, Yu in view of Micromod and Yap teaches the method of claim 12 as discussed above.
Yu in view of Micromod and Yap fail to teach wherein the pathogen is influenza A virus (Applicant’s elected species).
Lu teaches wherein the pathogen is influenza A virus (Abstract). Lu further teaches that “[i]nfluenza A has emerged recently as a potential significant risk to human populations…the opportunity exists for a worldwide pandemic…in 1918 a global influenza epidemic resulted in an estimated 20-40 million deaths. With increased population density today, higher mortality is likely” (paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yu in view of Micromod and Yap to rely on the pathogen being influenza A virus taught by Lu because Lu teaches that influenza A may result in a highly lethal pandemic. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu in view of Micromod and Yap and Lu teach methods for detecting and/or characterizing pathogens present in an isolated test sample using particles with immobilized ligands.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of Micromod, Yap, Schwind and Khojasteh et al. Letters in Applied Microbiology, 36, 372–376 (2003) as evidenced by Lapierre et al. TRANSFUSION Volume 30, Issue 2, February 1990, Pages 109-113 https://doi.org/10.1046/j.1537-2995.1990.30290162894.x and Zhu et al. Cell Death Discovery (2024) 10:415 https://doi.org/10.1038/s41420-024-02180-3.
Regarding claim 14, Yu suggests a method for detecting and/or characterizing pathogens present in an isolated test sample (Title, Abstract), the method comprising: (a) contacting in a vessel comprising a bottom and a wall, and in a buffered aqueous liquid solution the sample with coloured particles as defined in claim 1 (page 717 col. 2 paras. 3-4). Regarding claim 1, Yu teaches a coloured spherical or substantially spherical particle, comprising: a core with a surface (Figure 1); and a pathogen ligand, wherein the pathogen ligand is immobilized on the surface of the core (page 717 col. 2 paras. 2-3); wherein at least the surface is coloured, and wherein the core of the particle is made of a silica-based material (Title). Yu further suggests (b) allowing the coloured particles to sediment by passive gravitational force for a time from 1 to 20 minutes after the contacting step (page 717 col. 2 para. 4); and (c) determining a sedimentation pattern of the coloured particles (Figures 2-6 and 8), and the assay takes place in the buffered aqueous liquid solution (page 717 col. 2 paras. 2-4, page 718 col. 1 para. 1, page 719 col. 2 para. 5).
Yu fails to teach detecting antibodies, the particle core having a material mass density from 1.5 to 2.5 g/cc and a diameter from 1 to 10 μm; wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl, wherein particle sedimentation on the bottom or walls of the vessel indicates presence of pathogen-binding antibodies in the sample, which antibodies inhibited pathogen binding to the coloured particles and particle agglutination, and wherein step (a) is performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core.
Micromod teaches “sicastar®-red, sicastar®-blue and sicastar®-black” (page 17). Micromod further teaches the particle core having a material mass density from 1.5 to 2.5 g/cc and a diameter from 1 to 10 μm (page 17 para. 2). Micromod further teaches wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl (page 17 para. 3). Micromod further teaches that “[t]he colored silica particles are produced by hydrolysis of orthosilicates and related compounds. They are extremely stable in organic solvents and buffers. No toxic effects come from the covalently bound dyes” (page 17 para. 3). Micromod further teaches the company’s contact information (page 17 footnote).
Yap teaches the “[d]evelopment of a slide latex agglutination test for rotavirus antigen detection” (Title). Yap further teaches the method comprising contacting a particle with a test sample, allowing the particles to sediment and determining the sedimentation pattern (page 2 col. 1 para. 4 and col. 2 para. 1). Yap further suggests wherein step (a) is performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core (page 55 col. 1 para. 3). Yap further suggests that performing step (a) at a pH that is higher than an average isoelectric point of the particle “causes the arms of the antibodies to be completely extended, thus allowing more effective contact and interaction with antigens” (page 55 col. 1 para. 3).
Schwind teaches a method for detecting and/or characterizing pathogen-binding antibodies present in an isolated test sample (Abstract, column 3 lines 47-49, “antibodies as analytes in the sample liquid e.g. antibodies to pathogens such as viruses (HIV, hepatitis viruses), bacteria or protozoa, antibodies to autoantigens, antibodies to tumours or antibodies to allergens.” column 4 lines 1-2) the method comprising:(a) contacting in a vessel comprising a bottom and a wall (Abstract, see Fig. 4) and in a buffered aqueous media (column 11 lines 46-47), the sample where antibodies are to be detected (column 4 lines 1-2), with coloured particles. Regarding the coloured particles, Schwind teaches a coloured particles (column 2 lines 4-7, column 3 lines 7-14) comprising: a core with a surface (column 2 lines 59-60, column 8 line 58). Schwind further teaches the core having a material mass density from 1.5 to 2.5 g/cc (column 2 lines 49-51) and a diameter from 1 to 10 µm (column 2 lines 46-48); and a pathogen ligand, wherein the pathogen ligand is immobilized on the surface of the core (column 3 lines 15-19); wherein at least the surface is coloured (column 3 lines 7-14), wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, and wherein R2 and R3 is independently selected from the group consisting of H and (C1-C8)-alkyl, and (C1-C8)-alkoxyl (column 3 lines 21-24). Schwind further teaches (b) allowing the coloured particles to sediment for a time from 1 to 20 minutes after the contacting step (column 4 lines 15-19, column 5 lines 51-52 and 56); and (c) determining a sedimentation pattern of the coloured particles (Abstract), wherein particle sedimentation on the bottom or walls of the vessel indicates presence of pathogen-biding antibodies in the sample (see Fig. 3 showing binding of the antibodies from the patient serum to the particles and forming a pellet in the wall of the vessel), wherein step (a) is performed at a pH in which the coloured particles have a net electrical surface charge (column 2 lines 53-56). Note that as evidenced by Lapierre, DiaMed erythrocyte gel immunoassays, i.e. DiaMed, are performed at a pH of 7.2 (page 111 column 2 paragraph 2). Schwind further teaches that the charge is provided by a combination of isoelectric points of pathogen ligand immobilized on the surface of the core of the coloured particles (column 3 lines 28-30 and 39-42, column 2 lines 4-7) and the charge of functional groups selected from -COO-R1, -NR2R3 on the surface of the core of the coloured particles (column 3 lines 21-24). Note that Schwind inherently provides a net negative charge when teaching that the assay is performed under standard conditions (neutral pH as evidenced by Lapierre) and when teaching that the ligand is a glycoprotein and functional group is a carboxyl. As evidenced by Zhu, “[s]ialic acids are predominantly found at the terminal ends of glycoproteins” (Abstract). Zhu further teaches that “[s]ialic acid is recognized as an anti-adhesive glycotype, significantly influencing the biophysical properties of sialylated cells. A prime example is the erythrocyte, which is heavily sialylated and negatively charged” (page 2 column 2 paragraph 2). Therefore, the glycoprotein and carboxyl groups in the neutral pH will inherently provide a net negative electrical surface charge to the particles. Schwind further teaches that detecting antibodies to various types of pathogens such as viruses, bacteria or protozoa, autoantigens, tumours and allergens can be used for screening of these diseases in body fluid samples (col. 4 line 67 and col. 5 lines 1-10).
Khojasteh teaches “[d]etection of antibodies to Staphylococcus aureus Toxic Shock Syndrome Toxin-1 using a competitive agglutination inhibition assay” (Title). Khojasteh further teaches which antibodies inhibited pathogen binding to the particles and particle agglutination (“[w]hen challenged with latex sensitized with anti-TSST-1 antibody, specific anti-TSST-1 antibodies present in the patient’s serum would inhibit the agglutination reaction with a predetermined amount of TSST-1 and a pellet would form in a microtitre plate well instead of the expected lattice agglutination pattern” page 373 column 1 paragraph 2). Khojasteh further teaches that “[t]he CAIA assay is relatively cheap and easy to perform, and can be performed on individual sera when required” (page 375 column 2 paragraph 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Yu to rely on the particle core having a material mass density from 1.5 to 2.5 g/cc, a diameter from 1 to 10 μm and wherein the surface comprises one or more functional groups selected from the group consisting of -COO-R1, -NR2R3 and combinations thereof, wherein R1 is independently selected from the group consisting of H and (C1-C8)-alkyl, wherein R2 and R3 are independently selected from the group consisting of H, (C1-Cs)alkyl, and (C1-C8)-alkoxyl, taught by Micromod because Micromod suggests that this enables the particles to be "extremely stable in organic solvents and buffers" (page 17 para. 3). A person having ordinary skill in the art would have had a reasonable expectation of success because Micromod teaches the production method of the particles and teaches their contact information.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Yu in view of Micromod to rely on wherein step (a) being performed at a pH that is higher than an average isoelectric point of the particle, the average isoelectric point provided by a surface electrical charge of the pathogen ligand immobilized on the surface of the core and the functional groups selected from -COOR1, -NR2R3 also on the surface of the core taught by Yap because Yap teaches that this enables the particles to have more effective contact and interaction with pathogens. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu and Yap teach methods of detecting and/or characterizing pathogens present in an isolated test sample comprising: contacting a particle with a test sample, allowing the particles to sediment and determining the sedimentation pattern.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Yu in view of Micromod and Yap to rely on the detecting of antibodies and wherein particle sedimentation on the bottom or walls of the vessel indicates presence of pathogen-biding antibodies in the sample taught by Schwind because Schwind teaches that this enables the detection of antibodies to various types of pathogens such as viruses, bacteria or protozoa, autoantigens, tumours and allergens which can be used for screening of these diseases in body fluid samples. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu in view of Micromod and Yap and Schwind teach (a) contacting in a vessel comprising a bottom and a wall, and in a buffered aqueous media, the sample with coloured particles, wherein the colored particles have a mass density from 1.5 to 2.5 g/cc and a diameter from 1 to 10 μm, allowing the coloured particles to sediment for a time from 1 to 20 minutes after the contacting step; and (c) determining a sedimentation pattern of the coloured particles wherein step (a) is performed at a pH that is higher than an average isoelectric point of the particle.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yu in view of Micromod, Yap and Schwind to rely on the antibodies inhibiting pathogen binding to the coloured particles and particle agglutination taught by Khojasteh because Khojasted suggests that this process is easy and cheap. A person having ordinary skill in the art would have had a reasonable expectation of success because Yu in view of Micromod, Yap and Schwind and Khojasted teach detecting pathogen-binding antibodies using particles.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of Micromod, Yap, Schwind and Khojasteh, as applied to claim 14 above, and further in view of Lu et al. (WO 2007018843 A2) (“Lu”).
Regarding claim 24, Yu in view of Micromod, Yap, Schwind and Khojasteh teach the method of claim 14 as discussed above.
Yu in view of Micromod, Yap, Schwind and Khojasteh fail to teach wherein the pathogen is influenza A virus (Applicant’s elected species).
Lu “provides method and compositions for determining the presence and amount of an influenza virus in a sample including high risk strains of Influenza A” (Abstract). Lu further teaches that “[i]nfluenza A has emerged recently as a potential significant risk to human populations…the opportunity exists for a worldwide pandemic…in 1918 a global influenza epidemic resulted in an estimated 20-40 million deaths. With increased population density today, higher mortality is likely” (paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Yu in view of Micromod, Yap, Schwind and Khojasteh to rely on the pathogen being influenza A virus taught by Lu because Lu teaches that influenza A may result in a highly lethal pandemic. A person having ordinary skill in the art would have had a reasonable expectation of success because both Yu in view of Micromod, Yap, Schwind and Khojasteh and Lu teach methods for detecting and/or characterizing pathogens present in an isolated test sample using particles with immobilized ligands. Furthermore, Yu in view of Micromod, Yap, Schwind and Khojasteh and Lu both teach wherein the pathogen is a virus.
Response to Arguments
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
Regarding the prior art rejections, Applicant argues that “ Schwind requires that the agglutination reagent penetrates an inert matrix. The inert matrix is a gel. The inert matrix/gel cannot be considered a liquid solution. Thus, contrary to the claims, Schwind does not disclose that the assay takes place in liquid solution. Moreover, Schwind does not disclose agglutination reagent particles made of silica-based material.” (page 13 paras. 5-6). However, new grounds of rejection are set forth above that relies on Yu as the primary reference. Yu teaches that the assay takes place in liquid solution and that the agglutination reagent particles are made of silica-based material (see rejection above). Applicant further argues that “Schwind does not disclose contacting the sample with the coloured particles in step (a) at a pH that is higher than an average isoelectric point of the particle” (page 13 para. 7). However, new grounds of rejection are set forth above in view of Yap. Yap suggests step (a) at a pH that is higher than an average isoelectric point of the particle (see rejection above). Applicant further argues that “Khojasteh do not cure the above-described deficiencies of Schwind, and thus claim 14 is also patentable over the combination of Schwind and Khojasteh for the same reason… The secondary references cited by the Examiner do not cure the above-described deficiencies of Schwind and Khojasteh. Thus, claims 12 and 14 are patentably allowable over the combination of the cited references. Claims 13, 17 and 24 depend from their respective claims 12 and 14 and are patentably allowable for at least the same reason” (page 14 paras. 1-3). However, new grounds of rejection are set forth above that do not rely on Khojasteh or Lu for curing the deficiencies of Schwind (see rejection above). Applicant further argues that “[t]he skilled person in view of Schwind would have no reason to select silica particles… It is also clear that Schwind does not motivate a skilled person to dispense with the inert matrix and carry out the assay in liquid solution. Moreover, even if Schwind contemplates gravitational forces for sedimentation (which it does not), this will be no more than a general statement contradicted by the complete teachings of this document, as evidenced in claim 1 and all the examples. In view of Schwind, a skilled person would not be motivated to make use of passive gravitational forces for sedimentation and would apply centrifugal forces (page 14 paras. 4-5). However, new grounds of rejection are set forth above that rely on Yu as the primary reference (see rejection above). Yu teaches silica particles, carrying out the assay in liquid solution and using gravitational forces for sedimentation (see rejection above). Applicant further argues that “[a]lso, the selection of the silica-based particles of size and density as claimed in combination with contacting the sample and the particles at a pH that is higher than the average isoelectric point of the particle enables that the result (sedimentation pattern and thus pathogen detection) is observable with the naked eye without instrumentation and in a very short time. This combination of features are neither taught nor suggested by Schwind alone or in combination with the remaining cited documents” (page 15 para. 1). However, new grounds of rejection are set forth above that rely on at least Yu in view of Micromod and Yap. Yu in view of Micromod and Yap address silica-based particles of size and density as claimed in combination with contacting the sample and the particles at a pH that is higher than the average isoelectric point of the particle, thereby enabling that the result (sedimentation pattern and thus pathogen detection) is observable with the naked eye without instrumentation and in a very short time (see rejection above).
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Fernando Ivich/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678