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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/15/2025 has been entered.
Status of the Claims
Claims 1-27 have been cancelled. Claims 46-47 have been withdrawn. Therefore, claims 28-45 are pending and currently under examination (claim set filed on 06/04/2025).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/13/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawal of Rejections
The response and amendments filed on 06/04/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 103 for obviousness have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection are set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 112(a), New Matter
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.
Claims 28-45 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 28 has been amended to recite “wherein the outer surface of the coated particles is not coated with a genetically engineered protein comprising a pathogen-binding portion of a Mannose Binding Lectin fused to an Fc region of an immunoglobulin (FcMBL)”; however, there is not support for this amendment in the instant Specification as originally filed. Moreover, the instant Specification actually states “The Mannose Binding Lectin (MBL) protein may be a genetically engineered protein based on MBL. For example, it may be a genetically engineered protein comprising the pathogen-binding portion of MBL fused to an Fc region of an immunoglobulin (i.e., FcMBL)” (see, e.g., instant Specification, pg. 42). Therefore, recitation of “wherein the outer surface of the coated particles is not coated with a genetically engineered protein comprising a pathogen-binding portion of a Mannose Binding Lectin fused to an Fc region of an immunoglobulin (FcMBL)” is new matter and should be removed from the instant claims (see, e.g., MPEP 608.04).
Claims 29-45 are included in this rejection for depending on rejection independent claim 28 and failing to rectify the noted deficiency.
Examiner’s Response to Arguments
Applicant stated that support for claim 28’s amendments can be found through the original application (remarks, page 7); however, here is no support in the instant Specification for Applicant’s amendment of claim 28. Therefore, this amendment is considered new matter under 35 U.S.C. 112(a).
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 28-34 and 36-44 are rejected under 35 U.S.C. 103 as being unpatentable over Cartwright (A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood, 2016 – previously cited) in view of Didar (Improved Treatment of Systemic Blood Infections Using Antibiotics with Extracorporeal Opsonin Hemoadsorption, 2015 – previously cited) and Wu (CN109741896; Date of Publication: May 10, 2019 – cited in the IDS filed on 12/29/2023 - newly cited).
Cartwright’s general disclosure relates to measuring the presence of pathogens from blood samples using a Mannose Binding Lectin linked to the Fc portion of human IgG1 (FcMBL) (see, e.g., Cartwright, pg. 218, “Introduction”, col 1). Additionally, Cartwright discloses that pathogen presence is measured through FcMBL binding to Pathogen Associated Molecular Patterns (PAMPs), in the presence and absence of antibiotics (see, e.g., Cartwright, pg. 218, “Introduction”, col 1).
Regarding claim 28(a) pertaining to incubating the sample with coated particles, Cartwright teaches incubating superparamagnetic microbeads coated with FcMBL with whole human blood, with and without antibiotic therapy, to capture PAMPs (see e.g., Cartwright, pg. 220, sections 4.1 and 4.2, Figure 2).
Regarding claims 29-30 and 32 pertaining to the recovered viable microorganisms, Cartwright teaches the detection and characterization of “intact viable bacteria” that were captured by the FcMBL microbeads (see, e.g., Cartwright, pg. 221, Table 1). Additionally, Cartwright teaches a FcMBL Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) methodology to detect whole pathogens (see, e.g., Cartwright, pg. 220, section 4.1 and Figure 2).
Regarding claim 31 pertaining to the detection of viable microorganisms, Cartwright teaches that the presence of FcMBL-coated magnetic microbeads binding to whole pathogens is indicative of infection (see, e.g., Cartwright, pg. 220, Figure 2).
Regarding claim 38 pertaining to the microorganism being a bacterium or fungus, Cartwright teaches binding of clinical pathogen isolates, including bacteria and fungi, by FcMBL (see, e.g., Cartwright, pg. 221, Table 1).
Regarding claim 39 pertaining to the antimicrobial agent being an antibiotic or antifungal, Cartwright teaches the use of bactericidal antibiotics, such as cefepime or meropenem (see, e.g., Cartwright, pg. 220, Figure 2 & pg. 221, Table 1).
Regarding claim 40 pertaining to the sample being a clinical sample, Cartwright teaches that the FcMBL ELLecSA was able to rapidly detect >80% of infection in human patients despite whether or not they were receiving antibiotic therapy (see, e.g., Cartwright, pg. 225, discussion).
Regarding claim 41 and claim 42 pertaining to the sample, Cartwright teaches that blood samples were collected from patients (see, e.g., Cartwright, pg. 218, section 2.1.2).
Regarding claim 43 pertaining to the coated particles being magnetic, Cartwright teaches superparamagnetic microbeads coated with FcMBL were used to capture and magnetically collect PAMPs (see, e.g., Cartwright, pg. 220, section 4.1).
Regarding claim 44 pertaining to the coated particles comprising a polymeric surface, Cartwright teaches the FcMBL microbeads, which are a comprised of a “carbohydrate recognition domain of Mannose Binding Lectin linked to the Fc portion of human IgG1” (see, e.g., Cartwright, pg. 218, introduction).
However, Cartwright does not teach: separating the particle-microorganism complexes from the antimicrobial agent to recover viable microorganisms from the culture (claim 28(b)); or incubating and/or culturing recovered viable microorganisms (claim 28(c)); or wherein the outer surface of the coated particles is not coated with a genetically engineered protein comprising a pathogen-binding portion of a Mannose Binding Lectin fused to an Fc region of an immunoglobulin (FcMBL) (claim 28); or wherein the sample comprises non-microorganism cells (claim 33); or separating the particle-microorganism complexes from the antimicrobial agent to recover viable microorganisms from the sample is performed in the absence of a detergent (claim 34); or that separating the particle-microorganism complexes from the antimicrobial agent to recover viable microorganisms from the sample comprises washing the separated particle-microorganism complexes (claim 36); or separating the particle-microorganism complexes from the antimicrobial agent to recover viable microorganisms from the sample through use of a magnetic field or centrifugation (claim 37).
Didar’s general disclosure relates to the development of a extracorporeal hemoadsorption device that is comprised of hollow fiber filters coated with FcMBL that can cleanse of broad range of pathogens from blood without having to first determine their activity (see, e.g., Didar, abstract).
Regarding claim 28(b) pertaining to separating the particle-microorganism complexes from the antimicrobial agent, Didar teaches “eluting the captured pathogens bound to the FcMBL” by “flowing calcium-free buffer through the lumen of the hollow fibers” in order to recover pathogens (see, e.g., Didar, pg. 388, section 3.2).
Regarding claim 28(c) pertaining to incubating and/or culturing the recovered viable microorganisms, Didar teaches that recovered fungi and bacteria were cultured on LB agar and at 30oC and 37oC, respectively, to determine the pathogen concentration in samples from the FcMBL binding (see, e.g., Didar, section 2.3, pg. 384)
Regarding claim 33 pertaining to non-microorganism cells, Didar teaches that the FcMBL hemoadsorption filter can remove bacteria and fungi from blood (see, e.g., Didar, abstract).
Regarding claim 34 pertaining to separating particle-microorganism complexes in the absence of a detergent, Didar teaches separating the captured pathogens bound to the FcMBL by using calcium-free buffer (see, e.g., Didar, pg. 388, section 3.2).
Regarding claim 36 pertaining to washing the separated particle-microorganism complexes, Didar teaches washing the FcMBL-microorganism complexes with “calcium-free medium or calcium chelators by leveraging the calcium-dependent binding of FcMBL (see, e.g., Didar, pg. 388, section 3.2 & pg. 391, discussion).
Regarding claim 37 pertaining to using a magnetic field or centrifugation, Didar teaches that pathogens are captured using “magnetic nanobeads coated with FcMBL” and removing the pathogens bound to nanobeads coated with FcMBL by “applied magnetic forces” (see, e.g., Didar, pg. 390, discussion).
Wu’s general disclosure relates to “a functionalized magnetic nanoparticle for broad-spectrum capture of bacteria and release of live bacteria, which is a magnetic nanoparticle with surface-modified ε- polylysine. The ε-polylysine-modified magnetic nanoparticles can capture gram-positive bacteria and gram-negative bacteria through electrostatic interaction, have broad-spectrum capture ability, high capture efficiency, short time, and low modification cost. It can be applied to the enrichment of bacteria in actual samples” (see, e.g., Wu, English Translation, Abstract).
Regarding claim 28 pertaining to the particles not being coated with FcMBL, Wu teaches magnetic nanoparticles for broad-spectrum capture if bacteria and release of live bacterial, wherein the magnetic nanoparticle is surface-modified with ε-polylysine (see, e.g., Wu, English Translation, Abstract).
It would have been first obvious to one of ordinary skill in the art to incubate a sample containing microorganisms with FcMBL-coated microbeads, as taught by Cartwright, to recover and culture viable microorganisms by separating the captured microorganism(s) from the FcMBL-coated microbeads, as taught by Didar. One would have been motivated to do so because Didar teaches the use of the FcMBL-coated microbeads to treat a systemic blood infection by capturing microorganisms in patient’s blood (see, e.g., Didar, abstract). Moreover, Cartwright teaches the use of FcMBL-coated microbeads for capturing whole microorganisms in clinical samples, which is indicative of infection (see, e.g., Cartwright, pg. 220, section 4.1 and Figure 2). Therefore, based on the teachings of Cartwright and Didar, it would have been obvious to use FcMBL-coated microbeads to capture microorganisms from blood samples. One would have expected success since Cartwright and Didar both teach the use of FcMBL-coated microbead composition for microorganism capture and recovery in blood.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute Cartwright’s FcMBL-coated microbeads with Wu’s magnetic nanoparticles surface-modified with ε-polylysine. One would have been motivated to do so because Wu teaches that “ε-polylysine-modified magnetic nanoparticles can capture gram-positive bacteria and gram-negative bacteria through electrostatic interaction, have broad-spectrum capture ability, high capture efficiency, short time, and low modification cost” (see, e.g., Wu, English Translation, Abstract). Moreover, Cartwright teaches the use of FcMBL-coated microbeads for capturing whole microorganisms in clinical samples, which is indicative of infection (see, e.g., Cartwright, pg. 220, section 4.1 and Figure 2). Therefore, based on the teachings of Cartwright and Wu, it would have been obvious to substitute Cartwright’s FcMBL-coated microbeads for Wu’s nanoparticles surface-modified with ε-polylysine. One would have expected success because Cartwright and Wu both teach capturing whole, live bacteria from clinical samples with coated beads.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Cartwright, Didar, and Wu as applied to claims 28-34 and 36-44 above, and in further view of Van Meerbergen (US2013/0171615; Date of Publication: July 4, 2013 – previously cited).
The combined teachings of Cartwright and Didar, herein referred to as modified-Cartwright-Didar, are discussed above as it pertains to recovering viable microorganisms from samples through incubation with magnetic particles coated with FcMBL.
However, modified-Cartwright-Didar does not teach: the selective lysis of non-microorganism cells in the sample whilst retaining intact microorganisms present in the sample (claim 35).
Van Meerbergen’s general disclosure relates to methods for the selective lysis of eukaryotic cells in a sample comprising microorganisms, such as bacteria (see, e.g., Van Meerbergen, abstract). Moreover, Van Meerbergen discloses “The selective lysis is obtained by incubating the sample in a non-ionic detergent under alkaline conditions” (see, e.g., Van Meerbergen, abstract) in order to allow for further cultivation and classification of the microorganisms present in the sample (see, e.g., Van Meerbergen, [0003]-[0004])..
Regarding claim 35 pertaining to selective lysis of non-microorganism cells, Van Meerbergen teaches selectively lysing eukaryotic cells, in a sample with microorganisms, by adding “a non-ionic detergent and a buffer to the sample to obtain a solution with a pH of about 9.5 or more” (see, e.g., Van Meerbergen, [0011]).
It would have been obvious to one of ordinary skill in the art to recover microorganisms in the sample, as taught by modified-Cartwright-Didar-Wu, by selectively lysing non-microorganism cells, as taught by Van Meerbergen. One would have been motivated to do so in order to isolate viable microorganisms from the culture for further cultivation and classification (see, e.g., Van Meerbergen, [0003]-[0004]). Moreover, modified-Cartwright-Didar-Wu teaches that recovered fungi and bacteria were cultured on LB agar and at 30oC and 37oC, respectively, to determine the pathogen concentration in samples from the FcMBL binding (see, e.g., Didar, section 2.3, pg. 384) and that the presence of whole pathogens is indicative of infection (see, e.g., Cartwright, pg. 220, Figure 2). Furthermore, modified-Cartwright-Didar-Wu teaches that ε-polylysine-modified magnetic nanoparticles can capture gram-positive bacteria and gram-negative bacteria through electrostatic interaction, have broad-spectrum capture ability, high capture efficiency, short time, and low modification cost (see, e.g., Wu, English Translation, Abstract). Therefore, based on the teachings of modified-Cartwright-Didar-Wu and Van Meerbergen, it would have been obvious to selectively lyse non-microorganism cells from samples in order to obtain, isolate, and grow microorganisms of interest from blood samples, which would be indicative of infection. One would have expected success because modified-Cartwright-Didar-Wu and Van Meerbergen both teach the recovery of microorganisms from samples.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Cartwright, Didar, and Wu as applied to claims 28-34 and 36-44 above, and in further view of Kang (An Extracorporeal Blood-Cleansing Device for Sepsis Therapy, 2014 – previously cited).
The combined teachings of Cartwright and Didar, herein referred to as modified-Cartwright-Didar, are discussed above as it pertains to recovering viable microorganisms from samples through incubation with magnetic particles coated with FcMBL.
However, modified-Cartwright-Didar does not teach wherein the coated particles comprise, on the outer surface, either (i) carboxylic acid groups, (ii) amino groups, (iii) hydrophobic groups, and/or (iv) streptavidin (claim 45).
Kang’s general disclosure relates to a blood-cleansing device for sepsis therapy, which allows for continuous removal of pathogens and toxins from blood (see, e.g., Kang, abstract). Additionally, Kang discloses the capturing of pathogens through use of magnetic nanobeads that are coated with mannose-binding lectin (MBL) (see, e.g., Kang, abstract).
Regarding claim 45 pertaining to the coated particles, Kang teaches that the “FcMBL was biotinylated at its N terminus by addition of the tripeptide sequence alanine-lysine-threonine”, which comprises carboxylic acid groups (see, e.g., Kang, pg. 1212, results). Kang teaches that “The Fc-containing MBL (FcMBL) was biotinylated at its N terminus by addition of the tripeptide sequence alanine-lysine-threonine. Site-specific biotinylation of the terminal tripeptide sequence enabled us to uniformly orient FcMBL at high density on the surface of streptavidin-coated superparamagnetic nanobeads (128-nm diameter) to create multivalent magnetic opsonins”, and that the recombinant FcMBL nanobeads exhibited activity against a broad range of Gram-positive and Gram-negative bacteria, as well as antibiotic-resistant bacteria and yeast (see, e.g., Kang, pg. 1212, results).
It would have been obvious to one of ordinary skill in the art to recover viable microorganism from a biological sample, as taught by modified-Cartwright-Didar-Wu, wherein recovery involves the use of FcMBL-coated microbeads with the outer surface containing carboxylic acid groups, as taught by Kang. One would have been motivated do so because Kang teaches “The Fc-containing MBL (FcMBL) was biotinylated at its N terminus by addition of the tripeptide sequence alanine-lysine-threonine. Site-specific biotinylation of the terminal tripeptide sequence enabled us to uniformly orient FcMBL at high density on the surface of streptavidin-coated superparamagnetic nanobeads (128-nm diameter) to create multivalent magnetic opsonins”, and that the recombinant FcMBL nanobeads exhibited activity against a broad range of Gram-positive and Gram-negative bacteria, as well as antibiotic-resistant bacteria and yeast (see, e.g., Kang, pg. 1212, results). Moreover, modified-Cartwright-Didar-Wu teaches that the use of FcMBL-coated magnetic microbeads binding to whole pathogens is indicative of infection (see, e.g., Cartwright, pg. 220, Figure 2), and that FcMBL-coated magnetic microbeads can bind to a range of Gram-positive bacteria, Gram-negative bacteria, and fungi (see, e.g., Cartwright, pg. 221, Table 1). One would have expected success since modified-Cartwright-Didar-Wu and Kang both teach the same FcMBL-coated microbead composition, microorganism capture, and microorganism recovery from the blood.
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 06/04/2025 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior arts of record.
In response to Applicant’s arguments that Cartwright and Didar do not teach the methods are presently claimed in view of the amendment of claim 28 (remarks, pages 8-9), as discussed above in regards to the 35 U.S.C. 103 rejection, this rejection has been withdrawn. However, new grounds are rejection have been made in light of claim 28’s amendments. Although Cartwright and Didar are relied upon in the above presented rejection, they are not relied in the rejection above to teach “wherein the outer surface of the coated particles is not coated with a genetically engineered protein comprising a pathogen-binding portion of a Mannose Binding Lectin fused to an Fc region of an immunoglobulin (FcMBL)”. Therefore, Applicant’s arguments are moot.
Conclusion
Claims 28-45 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/NGHI V NGUYEN/Primary Examiner, Art Unit 1653