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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 20 November 2025 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 20 November 2025.
CLAIMS UNDER EXAMINATION
Claims 1-2, 6, 8, 11, 15-16, 20, 27-28, 35-37, 42-45 and 48-51 have been examined on their merits.
PRIORITY
Provisional Application 62/374,192, filed 2016 August 12, does not provide support for synthetic red and white blood cells.
WITHDRAWN REJECTIONS
The arguments made in the response filed on 20 November 2025 are acknowledged.
The previous rejections have been withdrawn due to claim amendment.
NEW GROUNDS OF REJECTION
New rejections have been necessitated by claim amendment.
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.
Claim 48 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.
Claim 48 recites “the method of claim 1”. Claim 1 is not directed to a method. Therefore the metes and bounds of the claim are unclear. Appropriate correction is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 20 recites the control composition comprises a nucleic acid that is a control target of interest. The base claim recites the target components of interest are selected from a group consisting of a virus (inactivated or attenuated), a plasmid, bacteria, fungi, a parasite, microbiota, an engineered cell line and wild type cells. A nucleic acid does not further limit the components recited in the base claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 1-2, 6, 8, 20, 27-28, 36-37, 42-45 and 48-51 are rejected under 35 U.S.C. 103 as being unpatentable over Chiklis et al. (Nucleic Acid Amplification Controls. Patent 9127048 2015) in view of Ryan et al (White blood cell hematology control. US5262327A) and Simoes (previously cited; Antimicrobial mechanisms of ortho-phthalaldehyde action. J Basic Microbiol. 2007 Jun;47(3):230-42).
Chiklis et al. teach a control material (composition) for nucleic acid amplification based detection of microorganisms in biological samples (Abstract). The composition can be used to screen biological fluids or as a diagnostic tool for biological fluids from individuals suspected of harboring pathogenic microorganism (column 10, lines 62-67).
The composition comprises a purified microorganism and “a liquid matrix that simulates a biological fluid” (column 3, line 27).
Regarding the microorganism: the microorganism is a virus or parasite isolated from infected blood (column 4, lines 10-35). The microorganism is rendered non-pathogenic (column 4, lines 59-60). The microorganism is modified with a compound capable of crosslinking the surface proteins on the microorganism (column 5, lines 20-23). The art teaches a crosslinker to facilitate crosslinking of surface proteins. Particularly preferred homobifunctional reagents include dialdehydes such as paraformaldehyde, glyoxal, malondialdehyde, succinialdehyde, adipaldehyde, gluteraldehyde and phthaldehyde. The art teaches phthaldehyde can be used (column 6, lines 1-16).
Regarding the liquid matrix: The art teaches the inactivated microorganism is suspended in a liquid matrix comprising stabilized biological fluids which correspond to fluids from the which biological samples will be analyzed (see column 9, lines 53-59). The matrix can comprise synthetic matrices formulated to simulate biological fluids (column 9, lines 60-62).
While the art teaches a liquid matrix that simulated a biological fluid, the art does not red and white blood cells.
The art does not teach phthaldehdye with sufficient specificity to anticipate the claim
Ryan teaches a reference control comprising white blood cells, red blood cells and platelets (see column 4, lines 29-31). Cells are stabilized (column 1, lines 55-60). A platelet is broadly is broadly interpreted to read on a wild-type cell.
Simoes teaches ortho-phtalaldehyde (OPA; known as phthalaldehyde) binds to microbial membrane receptors due to cross-linkage; impairs the membrane functions allowing the biocide to enter through the permeabilized membrane; it interacts with intracellular reactive molecules, such as RNA, compromising the growth cycle of the cells and, at last, with DNA (Abstract).
It would have been obvious to use phthaldehyde as the crosslinker taught by Chiklis. Chiklis teaches a biofunctional crosslinker that crosslinks cells, and Simoes teaches phthaldehyde can be used to crosslink microbial cells. KSR Rationale E indicates that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and commonsense” (MPEP 2143 “Rationale E. Obvious to Try” section). One would have had a reasonable expectation of success since Chiklis identifies phthaldehyde as a crosslinker that can be used in the disclosed composition.
One would have expected similar results since both references use phtalaldehyde as a crosslinker.
It would have been obvious to use the stabilized cells taught by Ryan in the Chiklis liquid matrix. Chiklis teaches a liquid matrix comprising a stabilized biological fluid which correspond to fluids from the which biological samples will be analyzed. One would use red and white blood cells when analyzing a microorganism present in blood, which contains red blood cells, white blood cells and platelets. One would have had a reasonable expectation of success since Chiklis teaches the use of a liquid matrix that simulates a biological fluid. One would have expected similar results since both references are directed to composition that simulate a biological fluid. Therefore claim 1 is rendered obvious.
Chikles teaches the composition an comprise aldehydes (column 5, lines 40-41). Therefore claim 2 is rendered obvious.
Ryan teaches cells from human blood (see Example 1). Therefore claim 6 is included in this rejection.
Ryan teaches red blood cells. It is well known in the art that red blood cells contain proteins. The specification (PG Pub) discloses proteins can be within the cell ([0030]). A protein present in a red blood cells reads on claim 8.
Regarding claim 20: The claim recites the control serves as an internal control. This is an intended use. Because the composition of claim 1 is rendered obvious, it meets this claim limitation. Chiklis teaches a nucleic acid. Therefore claim 20 is included in this rejection. A nucleic acid is interpreted to be a chemical analyte. Therefore claim 36 is included in this rejection.
Chiklis teaches formaldehyde (column 5, line 64). Therefore claim 27 is included in this rejection.
Chiklis teaches NHS imidate (column 6, line 2). Therefore claim 28 is included in this rejection.
Chiklis teaches adding sucrose and mannose for long term storage and stability as stabilizers (column 10, lines 5-6). Therefore one or more organic compounds. Claim 37 is included in this rejection.
Regarding claims 42-43: the claims recite the time required for stabilization. The claims are directed to a product, and not a process. Because claim 1 is rendered obvious, it meets the limitations recited in the claims. Therefore claims 42-43 are included in this rejection.
Regarding claims 44-45: the claims recite limitations directed to the stability of the product. The prior art teaches stabilized components. Because the claimed product is rendered obvious, it meets the limitations recited in the claims. Therefore claims 44-45 are included in this rejection.
Chiklis teaches hydrazide (column 6, line 4). Therefore claim 48 is included in this rejection.
Claims 49-50 recite synthetic or engineered red blood cells. This is a product by process limitation that does not distinguish the claimed cells from those taught by Ryan. Therefore claims 49-50 are included in this rejection.
Chiklis teaches the liquid matrix can contain antibiotics (column 9, line 65). An antibiotic is broadly interpreted to be a biocide. Therefore claim 51 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Chiklis in view of Ryan et al. and Simoes as applied to claim 8 above, and further in view of
Das et al. (Method of preparing controls for glycated hemoglobin s-a1c derived from healthy blood cells. US 20120129147 A1).
Claim 8 is rejected on the grounds stated above. A composition comprising red blood cells is rendered obvious. The teachings of the prior art are reiterated. Red blood cells inherently contain proteins. The art does not disclose a protein exogenously modified to indicate glycosylation.
Das teaches a control composition comprising simulated red blood cells that include glycosylated hemoglobin (a protein) ([0002]). The composition is used to mimic diabetic blood ([0010]). Das teaches a control composition ([0012]).
It would have been obvious to use red blood cells comprising glycosylated hemoglobin in the control composition taught by Chiklis. Chiklis teaches a liquid matrix that mimics a biological fluid. One would have been motivated to simulate blood from a diabetic patient. One would have had a reasonable expectation of success since Das teaches the cells can be used in a control composition. One would have expected similar results since the references are directed to biological control compositions. Therefore claim 11 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Chiklis in view of Ryan et al. and Simoes as applied to claim 1 above, and further in view of Giamarellou et al. (Multidrug-resistant Gram-negative bacteria: how to treat and for how long. International Journal of Antimicrobial Agents. Volume 36, Supplement 2, December 2010, Pages S50-S54).
Claim 1 is rejected on the grounds stated above. The teachings of the prior art are reiterated. Chiklis teach an infectious microorganism. The composition can be used to screen biological fluids or as a diagnostic tool for biological fluids from individuals suspected of harboring pathogenic microorganism. The art does not teach a Gram-negative organism that has a mechanism of drug or treatment resistance.
Giamarellou teaches multidrug-resistant (MDR) Gram-negative bacilli (Abstract).
The emergence of multidrug-resistant (MDR) Gram-negative bacilli is a growing problem (page S50, left column, first paragraph).
It would have been obvious to try using MDR gram-negative bacteria in the composition taught by Chiklis. Chiklis teaches an infections microorganism and the Giamarellou teaches MDR Gram-negative bacteria is an infections microorganism with drug resistance. One would have been motivated to use an MDR gram negative bacteria to prepare a control composition for this pathogen. One would have had a reasonable expectation of success since Chiklis teaches any microorganism can be used in the disclosed composition. Therefore claim 15 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Chiklis in view of Ryan et al. and Simoes as applied to claim 1 above, and further in view of Illinois Department of Public Health (MRSA Methicillin-Resistant Staphylococcus aureus. 2007).
Claim 1 is rejected on the grounds stated above. The teachings of the prior art are reiterated. Chiklis art teaches a composition to detect an infectious microorganism (column 3, lines 65-66).
The art does not teach a Gram-positive organism that has a mechanism of drug or treatment resistance.
The Illinois Department of Public Health teaches Staphylococcus aureus is a bacterium that is commonly carried in the nose and on the skin of healthy people (first paragraph). A bout 1 percent of persons have a type of staph resistant to these antibiotics called methicillin- resistant staph aureus, which is often referred to as MRSA. (first paragraph). It is well known in the art that Staphylococcus aureus is gram positive.
It would have been obvious to try using MRSA in the composition taught by Chiklis. Chiklis teaches an infections microorganism and the Illinois Department of Health teaches MRSA is an infections microorganism with drug resistance. One would have been motivated to use MRSA to prepare a control composition for this pathogen. One would have had a reasonable expectation of success since Chiklis teaches any microorganism can be used in the disclosed composition. Therefore claim 16 is included in this rejection.
Therefore Applicant’s invention is rendered obvious as claimed.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Chiklis in view of Ryan and Simoes as applied to claim 1 above, and further in view of Ryan et al. (previously cited; Method for differential determination of white blood cells using diazolidinyl urea to stabilize white blood cells. Patent US5250438).
Claim 1 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. Chiklis teaches a stabilized liquid matrix. Ryan teaches stabilized blood cells. teaches a composition comprising blood cells and a stabilizing agent.
The art does not teach the use of diazolidinyl urea (claim 35).
Ryan et al. teaches a composition comprising red and white blood cells (Abstract). The art teaches diazolidinyl urea stabilized white blood cells (column 3, lines 9-10).
It would have been obvious to use diazolidinyl urea in the composition taught by Chiklis. One would have been motivated to do so to stabilize blood cells, as taught by Ryan (‘438). One would have had a reasonable expectation of success since Chiklis teaches the use of stabilized components and Ryan teaches blood cells can be stabilized using diazolidinyl urea . One would have expected similar results since both references are directed to compositions comprising blood components and stabilizers. Therefore claim 35 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653