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 .
Election/Restrictions
Applicant’s election without traverse of the species “HBV” in the reply filed on 6/8/2026 is acknowledged.
Claims 504-508 and 510-529 are pending.
Claims 511-513 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/8/2026. Applicant noted in their response of 6/8/2026 that claim 511 encompasses the elected species. However, claim 511 requires a combination of four different pathogens or infectious agents, and therefore does not encompass the elected species of the single elected pathogen (HBV).
Claims 504-508, 510, and 514-529 are being examined on the merits.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement (e.g., see pages 74, 76-77, 121-122 (non-exhaustive list)). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See pages 143, 145-155, and 593-596.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figures 12, 32, 33, 34, 35, 36, and 37.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The use of the terms “Tween” (pg 94), “Sephadex” and “Sephacryl” (pg 106), “Ficoll” (pg 120), and “OmniScript” and “SensiScript” (pg 122), which are trade names or marks used in commerce, have been noted in this application. These terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The examples above are not an exhaustive list of unmarked trade names or marks used in commerce throughout the specification. Please carefully read through and properly notate each instance.
Claim Rejections - 35 USC § 112a – Scope of Enablement
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 504-508, 510, and 514-529 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for
screening a plurality of donor blood or donor blood product samples to determine whether donor blood associated with the samples is acceptable for transfusion
does not reasonably provide enablement for using any type of sample for determination of whether or not donor blood is acceptable for transfusion. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Nature of the invention and breadth of the claims
The claims are broadly directed to the detection of one or more pathogens and/or infectious agents in any type of sample, comparison of this detection level to a pre-determined level of said pathogen and/or infectious agent in the sample, and then determination based on this comparison as to whether the donor blood is acceptable for transfusion.
Direction provided by the specification and working example
The specification provides working examples starting on page 586, in which the plurality of samples employed include plasma, serum, and whole blood. The specification lists other potential types of samples including “a blood product, such as for example, whole blood, platelets, red blood cells, and plasma…tissues, organs, vaccines, cells, gene therapy, and recombinant therapeutic proteins...saliva or oral fluid, sweat, tears, mucus, urine, lymphatic fluid, cerebrospinal fluid, interstitial fluid, [and] bronchoalveolar lavage fluid” (pg 42).
State of the art, level of skill in the art, and level of unpredictability
It is known in the art, as taught by Frankel et al. (Journal of Virological Methods, 2017) that different types of samples from a human can have different levels at different times relative to the time of infection depending on the source of the sample (Discussion). For example, Zika virus can be positive in urine while being negative in serum, and shows extended detection in whole blood compared to patient-matched plasma or serum, as well as urine (Discussion, paragraphs 3-4). Additionally, any type of sample could include hair, nail clippings, skin swab, etc. It is recommended, as taught by Frankel et al. and recommended by the FDA, that blood and blood components should be screened for donation (Introduction, paragraph 2).
Quantity of experimentation required
Given the level of unpredictability in terms of ability to detect a virus in varying sample types at reasonable levels of confidence, there would be an undue amount of experimentation required for one skilled in the art to perform the method of determination of transfusion acceptability using any type of sample as claimed.
Conclusion
After consideration of the teaching of the specification and the specific working examples, considering the breadth of the claims, and the unpredictability in the art, it is the conclusion that an undue and unreasonable amount of experimentation would be required to make and use the invention that is instantly claimed.
Claim Rejections - 35 USC § 112b - Indefiniteness
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 504-508, 510, and 514-529 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.
Claim 504 recites the limitation “wherein the result includes a determination of a predetermined level of nucleic acid from at least one of a plurality of pathogens or infectious agents”. It is unclear how the determination can be made in the nucleic acid analysis if level is already “predetermined”, by definition occurring before the analysis. Furthermore “the determination of a level less than the predetermined level indicates that the donor blood is acceptable for transfusion” is also unclear. It is unclear what “a level” is referring to. A level of a detected pathogen? Of a nucleic acid? It is unclear how the nucleic acid analysis is being applied with how the claim is currently written. For the purposes of examination, it is being interpreted that a level of at least one pathogen or infectious agent is determined in the nucleic acid analysis, and then if this level is less than a predetermined level (such as a limit of detection for a particular analysis or a threshold set by governing body, pg 176 and 192 of specification) of the same detected pathogen or infectious agent, then the donor blood is acceptable for transfusion. However, further clarification is required.
Claim 504 recites the limitation “screening a plurality of samples” and “performing a nucleic acid analysis on each sample of the plurality of samples”, “determining a result from the nucleic acid analysis”, and “each result has a time to result of about 20 to 45 minutes from initiation of the nucleic acid analysis”. However, the time limitation is unclear given that the number of samples is not specified. It is also unclear given that it is not specified if the time to result is for a single sample of the plurality of samples or for all of the samples at once or if the amplification and detection are taking place together or separately. Additionally, it is unclear what is meant by “from initiation of the nucleic acid analysis”. Does this mean from the loading of the sample, from the time the nucleic acid is extracted, etc. Clarification is required.
Claims 505-508, 510, and 514-529 depend from claim 504, inherit these deficiencies, and are rejected on the same basis.
Claims 506 and 507 recite “wherein at least about 140 results are obtained per hour per m2 of a footprint occupied by the automated system” and “wherein at least about 70 results are obtained per hour per m3 of a volume occupied by the automated system”. As noted above in the rejection of claim 504, it is unclear if the number of results pertains to a single result per plurality of samples (such as pooled samples) or if it pertains to a single result for a single sample, such as a single sample from a single donor.
Claim 514 recites the limitation "the plurality of samples of donor blood". There is insufficient antecedent basis for this limitation in the claim. The type of sample that comprises the plurality of samples is not specified in claim 504, from which claim 514 depends.
Claims 518, 519, 521, and 523 recite limitations that state time limitations for various processes within the sample preparation process as a whole (and for the lysis and wash processes within the sample preparation process) and for the amplification and detection process. However, as noted above, the number of samples is not specified. Therefore, it is unclear if this time requirement for completion for each step is for a single sample or for the entire plurality of samples. And if it is a plurality of samples, it is unclear how many samples are being processed.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “a sample preparation area for performing the sample preparation process” in claims 525 and 529, “a nucleic acid amplification area for performing the amplification process” in claims 525 and 529, “a nucleic acid detection area for performing the detection process” in claims 525 and 529, and “an amplification and detection system configured to perform the amplification process and the detection process simultaneously” in claim 527.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof. The specification provides embodiments and examples of structures that may be included in such areas, but no limiting definitions or limiting structural elements were provided. Therefore, the broadest reasonable interpretation of areas/structures that perform the cited functions will be interpreted as reading on said claims.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim 525 and 529 are directed to a system comprising a sample analysis station. The structural limitations provided for the sample analysis stations are that it comprises a sample loading area, a sample preparation area, a nucleic acid amplification area, and a nucleic acid detection area. However, no structural definitions provided in the specification indicate the said sample analysis station must be a single unitary device, merely that said station must comprise the components necessary for performing sample loading, sample preparation, amplification, and detection.
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.
Claims 504-505, 508, 510, 514-515, and 517-524 are rejected under 35 U.S.C. 103 as being unpatentable over Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) in view of Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015).
Claims 504 and 510: Roth teaches methods and apparatuses for screening multiple samples of donor blood. Roth teaches that this screening is necessary given the “risk of becoming infected with viral pathogens such as HIV 1/2, HCV, HBV, or HAV during a blood transfusion” (Abstract and pg 1), therefore teaching that the purpose of screening said samples is the determination of whether the samples are acceptable for transfusion. Roth teaches performing nucleic acid analysis on each of the plurality of samples comprising a sample preparation process, an amplification process, and a detection process (pg 8-9). Roth teaches a time to result for 48 samples of approximately 4 hours from the moment of loading said samples into an automated machine. Roth also teaches that a preferred embodiment of the method is capable of analyzing 3780 samples in 8 hours (pg 9). As noted in the 112b rejection above, the time to result of claim 504 is unclear given that no number of samples is specified, and it is not clear if this is a time for each individual sample or for multiple samples at once. Given this ambiguity, it is being interpreted that the time to result of 20 to 45 minutes is for each individual sample, with the plurality of samples being any number of samples. Therefore, the methodology of Roth reads on this limitation given lack of clear constraints.
Roth does not teach that a determined level of nucleic acid is compared to a predetermined level of at least one of a plurality of pathogens or infectious agents. However, standard levels of pathogens/infectious agents that are deemed safe for blood donation are known in the art, as taught by Chigurupati.
Chigurupati teaches that the performance of nucleic acid amplification testing (NAT) of donor blood relies on the analytical sensitivity of the assay (Discussion). The analytical sensitivity acknowledged by the World Health Organization international standards calculated based on a 95% limit of detection for a pathogen such as HBV is 3.7 IU/mL (Discussion, paragraph 3; consonant with election of HBV). The limit of detection/analytical sensitivity as taught by Chigurupati for HBV is consistent with the “predetermined level” of HBV as described in claim 510 (HBV at a predetermined level of at least 1-10 IU/mL).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Roth to include a pre-determined level of viral identification as taught by Chigurupati for the safe release of donor blood that would prevent the transmission of viral pathogens through transfusion. One would be motivated to do so given the teaching by Chigurupati that this “pre-determined level” or standard level for NAT is an international standard for assay sensitivity, providing a 95% limit of detection, as set by an international health organization (e.g., the WHO; Discussion, paragraph 3). One would have a reasonable expectation of successfully identifying positive samples when applying this predetermined level given that this level of sensitivity is specifically for tests employing nucleic acid amplification for identification of viral pathogens in blood samples (the type of assay being employed by Roth).
Claim 505: Roth teaches that the nucleic acid analysis and determining a result are performed on an automated system (page 4, 10).
Claim 508: Roth teaches that the pathogen or infectious agent is HBV (pg 8, 13-15).
Claim 514: Roth teaches that at least one of the plurality of samples of donor blood is a pooled sample (pg 3, 613-15).
Claim 515: Roth teaches that the sample preparation process comprises onboard pooling of a subset of the plurality of samples (pg 6-7).
Claim 517: Roth teaches that sample preparation comprises a lysis process and wash process (pg 4-5).
Claim 518, 519, 521, and 523: Roth teaches that 48 samples are processed through a sample preparation process (lysis and wash) in about 2.5 hours (pg 14). Roth teaches that amplification and detection takes about 2 hours for 48 samples (pg 15). As noted in the 112b rejection above, it is not clear if the limitations presented here (about 4 to about 8 minutes for the lysis process (claim 518), about 5 to about 9 minutes for the wash process (claim 519), about 12 to about 16 minutes for the sample preparation process (claim 521), about 1 to about 22 minutes (claim 523)) is a time for each individual sample or for multiple samples at once. Given this ambiguity, it is being interpreted that the claimed time is for each individual sample, with the plurality of samples being any number of samples. Therefore, the methodology of Roth reads on this limitation given lack of clear constraints.
Claim 520: Roth teaches that the wash process comprises at least one wash step and an elution step (pg 14).
Claim 522: Roth teaches that the amplification process and the detection process are performed together in an amplification and detection process (pg 9).
Claim 524: Roth teaches that the time to result ends with determination of the result (pg 15).
Claims 506-507 and 525-529 are rejected under 35 U.S.C. 103 as being unpatentable over Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) in view of Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015) as applied to claims 504-505, 508, 510, 514-515, and 517-524 above, and further in view of Aretzweiler (Aretzweiler et al., Expert Review of Molecular Diagnostics 2019) and Roche Diagnostics (cobas® 6800/8800 Systems User Guide Publication Version 4.2, 2018).
The teachings of Roth in view of Chigurupati as they apply to claims 504-505, 508, 510, 514-515, and 517-524 are detailed above. Relevant to the instantly rejected claim, Roth in view of Chigurupati teaches a method of screening a plurality of blood samples for pathogens and/or infectious agents to determine if donor blood is acceptable for transfusion. Roth in view of Chigurupati teaches performing this screening on an automated system which performs sample preparation, amplification, and detection and is comprised within the same housing (Roth, pg 10).
Roth in view of Chigurupati do not teach specific dimensions of said automated system or specify that said automated system comprises a sample loading area. However, automated systems which comprise a sample analysis station with a sample loading area, sample preparation area, nucleic acid amplification area, and and nuclid acid detection area are known in the art, as taught by Aretzweiler and Roche Diagnostics.
Claim 506-507: Aretzweiler teaches a high throughput automated system (cobas 6800) which can be used for testing blood samples for pathogens and/or infectious agents (Abstract). Aretzweiler teaches that the cobas 6800 is capable of processing 297 blood samples in about 7.5 hours (including loading of reagents and samples onto the machine, ~1hr see Figure 1a). The Roche Diagnostics User Guide for the cobas 6800 specifies that the cobas 6800 machine is 2.16 m in height, 2.92 m in width, and 1.29 m in depth (page 290). The footprint of the machine is thus 3.8 m2 and the volume is 8.1 m3. According to the analysis taught by Aretzweiler of the processing times of 297 samples in 6.5 hours, the machine thus produces 12 results per hour per m2 and 5.6 results per hour per m3. As noted in the 112b rejection of claim 504 above, it is unclear when exactly the timing starts for determination of result output and it is unclear whether the results are for multiple samples or for a single sample. Given this ambiguity, the cobas 6800 as taught by Aretzweiler and Roche Diagnostics reads on the automated system of 506-507.
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have performed the method of Roth in view of Chigurupati with the automated cobas 6800 system as taught by Aretzweiler and Roche Diagnostics. One would be motivated to use this automated system given the teaching by Aretzweiler that said system is “designed to facilitate consolidation of multiple tests and increase workflow efficiency” (Introduction, paragraph 2). One would have a reasonable expectation of success given that the cobas 6800 system is design to screen blood samples for pathogens such as HBV through nucleic acid amplification assays, the same methodology as employed by Roth in view of Chigurupati (Methods, paragraphs 3-5).
Claim 525-527 and 529: Roche Diagnostics teaches a sample analysis station comprising a sample loading area (pg 31-32), a sample preparation area for performing the sample preparation process (pg 31, 37), a nucleic acid amplification area for performing the amplification process (pg 31), and a nucleic acid detection area for performing the detection process (pg 31, 40), wherein the nucleic acid amplification are and the nucleic acid detection area is a single area configured to perform the amplification process and the detection process simultaneously (pg 31, 40).
Claim 528: Roche Diagnostics teaches that the sample preparation area includes a wash and elution system (pg 37).
Claim 516 is rejected under 35 U.S.C. 103 as being unpatentable over Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) in view of Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015) as applied to claims 504-505, 508, 510, 514-515, and 517-524 above, and further in view of Holmes (Holmes et al., US 10,534,009 B2).
The teachings of Roth in view of Chigurupati as they apply to claims 504-505, 508, 510, 514-515, and 517-524 are detailed above. Relevant to the instantly rejected claim, Roth in view of Chigurupati teaches a method of screening a plurality of blood samples for pathogens and/or infectious agents to determine if donor blood is acceptable for transfusion. Roth in view of Chigurupati teach a sample preparation process that comprises preparing an eluate.
Roth in view of Chigurupati do not teach splitting the eluate into two or more amplification vessels. However, splitting of samples after processing into separate vessels is known in the art as taught by Holmes.
Holmes teaches a device that is capable of sample preparation, sample assay, and sample detection (Abstract). Holmes teaches the sample processing includes processes such as cell lysis and elution (col 116, ln 40-50). Holmes teaches that processing of a sample includes dividing the sample into portions (col 243, ln 64-67 – col 244, ln 1-56 and col 245, ln 24-35).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Roth in view of Chigurupati with that of Holmes to include separation of the eluate into two or more vessels for further analysis. One would be motivated to do so given the teaching by Holmes that this allows for separate aliquots of the same sample to be analyzed and/or further processed separately and potentially be exposed to differential preparation/treatment (col 243, ln 64-67 – col 244, ln 1-56 and col 245, ln 24-35). One would have a reasonable expectation of success given that Holmes teaches performing this splitting using an automated device and with samples such as blood samples (col 244, ln 3-4). While Holmes exemplifies splitting the blood sample into aliquots pre-processing/analysis, with respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 504-508, 510, and 514-515, and 517-524 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 8, 14, 17-18, 21-25, 27, and 31-32 of copending Application No. 18/557,610 in view of Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) and Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015).
Regarding claim 504 and 510: The claims of ‘610 teach an automated system for high throughput analysis of samples (claim 1) wherein the system performs sample preparation (claim 6-7) and nucleic acid analysis (claim 21) and performs detecting of pathogens and/or infectious agents such as HBV (claims 25 and 31-32). The claims of ‘610 teach determination of whether a sample of donor material is acceptable for clinical use based on the dtermination of the presence of a nucleic acid derived from at least one of a plurality of pathogens or infectious agents (claim 27). The claims of ‘610 teach that the sample can be blood (claims 17 and 20) and the specification of ‘610 defines “clinical use” as including transfusion (page 34).
The claims of ‘610 do not teach that the nucleic acid analysis of the pathogens and/or infectious agents in the screening of donor samples for transfusion comprises nucleic acid amplification and detection or the times to results. However, use of nucleic acid amplification and detection of pathogens in donor samples for screening of acceptability for transfusion is known in the art, as taught by Roth.
Roth teaches methods and apparatuses for screening multiple samples of donor blood. Roth teaches that this screening is necessary given the “risk of becoming infected with viral pathogens such as HIV 1/2, HCV, HBV, or HAV during a blood transfusion” (Abstract and pg 1), therefore teaching that the purpose of screening said samples is the determination of whether the samples are acceptable for transfusion. Roth teaches performing nucleic acid analysis on each of the plurality of samples comprising a sample preparation process, an amplification process, and a detection process (pg 8-9). Roth teaches a time to result for 48 samples of approximately 4 hours from the moment of loading said samples into an automated machine. Roth also teaches that a preferred embodiment of the method is capable of analyzing 3780 samples in 8 hours (pg 9). As noted in the 112b rejection above, the time to result of claim 504 is unclear given that no number of samples is specified, and it is not clear if this is a time for each individual sample or for multiple samples at once. Given this ambiguity, it is being interpreted that the time to result of 20 to 45 minutes is for each individual sample, with the plurality of samples being any number of samples. Therefore, the methodology of Roth reads on this limitation given lack of clear constraints.
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the apparatus of ‘610 to include the nucleic acid amplification and detection areas for screening of pathogens as taught by Roth. One would be motivated to do so given the assertion by Roth that usage of nucleic acid amplification technology (NAT) increases the “sensitive and direct detection of viral contamination in blood donations” and allows for showing of positive results as early as possible as compared to immunoassays (page 2). One would have a reasonable expectation of success given that Roth also teaches detecting pathogens such as HBV on an automated system.
The claims of ‘610 in view of Roth do not teach that a determined level of nucleic acid is compared to a predetermined level of at least one of a plurality of pathogens or infectious agents. However, standard levels of pathogens/infectious agents that are deemed safe for blood donation are known in the art, as taught by Chigurupati.
Chigurupati teaches that the performance of nucleic acid amplification testing (NAT) of donor blood relies on the analytical sensitivity of the assay (Discussion). The analytical sensitivity acknowledged by the World Health Organization international standards calculated based on a 95% limit of detection for a pathogen such as HBV is 3.7 IU/mL (Discussion, paragraph 3; consonant with election of HBV). The limit of detection/analytical sensitivity as taught by Chigurupati for HBV is consistent with the “predetermined level” of HBV as described in claim 510 (HBV at a predetermined level of at least 1-10 IU/mL).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the apparatus of ‘610 in view of Roth to include a pre-determined level of viral identification as taught by Chigurupati for the safe release of donor blood that would prevent the transmission of viral pathogens through transfusion. One would be motivated to do so given the teaching by Chigurupati that this “pre-determined level” or standard level for NAT is an international standard for assay sensitivity, providing a 95% limit of detection, as set by an international health organization (e.g., the WHO; Discussion, paragraph 3). One would have a reasonable expectation of successfully identifying positive samples when applying this predetermined level given that this level of sensitivity is specifically for tests employing nucleic acid amplification for identification of viral pathogens in blood samples (the type of assay being implemented by the automated system of ‘610 in view of Roth).
Claim 517: Roth teaches that sample preparation comprises a lysis process and wash process (pg 4-5).
Claim 518, 519, 521, and 523: Roth teaches that 48 samples are processed through a sample preparation process (lysis and wash) in about 2.5 hours (pg 14). Roth teaches that amplification and detection takes about 2 hours for 48 samples (pg 15). As noted in the 112b rejection above, it is not clear if the limitations presented here (about 4 to about 8 minutes for the lysis process (claim 518), about 5 to about 9 minutes for the wash process (claim 519), about 12 to about 16 minutes for the sample preparation process (claim 521), about 1 to about 22 minutes (claim 523)) is a time for each individual sample or for multiple samples at once. Given this ambiguity, it is being interpreted that the claimed time is for each individual sample, with the plurality of samples being any number of samples. Therefore, the methodology of Roth reads on this limitation given lack of clear constraints.
Claim 520: Roth teaches that the wash process comprises at least one wash step and an elution step (pg 14).
Claim 522: Roth teaches that the amplification process and the detection process are performed together in an amplification and detection process (pg 9).
Claim 524: Roth teaches that the time to result ends with determination of the result (pg 15).
Claim 516 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 8, 14, 17-18, 21-25, 27, and 31-32 of copending Application No. 18/557,610 in view of Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) and Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015), as applied to claims 504-508, 510, and 514-515, and 517-524 above, and further in view of Holmes (Holmes et al., US 10,534,009 B2) according to citations and rationales provided above.
Claims 5525-529 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6, 8, 14, 17-18, 21-25, 27, and 31-32 of copending Application No. 18/557,610 in view of Roth (Roth et al., WO 2016/020455 A1; cited on IDS of 1/25/2024, #54) and Chigurupati (Chigurupati et al., Asian Journal of Transfusion Science 2015), as applied to claims 504-508, 510, and 514-515, and 517-524 above, and further in view of Aretzweiler (Aretzweiler et al., Expert Review of Molecular Diagnostics 2019) and Roche Diagnostics (cobas® 6800/8800 Systems User Guide Publication Version 4.2, 2018) according to citations and rationales provided above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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