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 .
Priority
This application 17/502,344 filed on 10/15/2020 does not claim priority to any domestic or foreign applications. The priority date of claim 1 and its dependent claims is determined to be 10/15/2020, the filing date of the instant application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/30/2025 has been entered.
Status of Claims
Claims 1, 14, and 16 are amended.
Claim 11 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-14 and 16 are pending and claims 1-10, 12-14, and 16 are under examination.
Response to Remarks filed 12/19/2025
The amendments and arguments presented in the papers filed 12/19/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/21/2025 listed below have been reconsidered as indicated.
a) The objection to claims 14 and 16 have been withdrawn in light of applicant’s amendments.
New and modified grounds of rejection necessitated by amendment are detailed below.
Claim Interpretation
Claims 1 and 14 recite the limitation “avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium”. “Avoiding a use” does not exclude the use of a material. Instead this limitation is interpreted under the broadest reasonable interpretation as an intention and does not limit the scope.
Claim Rejections - 35 USC § 112(b)
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 1-10, 12-14 and 16 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 1 recites the limitation “avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium” and are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 1 recites the active steps “performing a (i) genetic test for infection by pathogens comprising two or more types of bacteria, performing a (ii) genetic test for infection by pathogens comprising a virus or a protozoon --- wherein the (i) genetic test comprises using at least one primer that targets a common base sequence among at least two types of bacteria to perform a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test for the virus or the protozoon comprises using at least one primer that selectively binds to a nucleic acid sequence of at least one type of a virus or a protozoon to perform an identification of a type of the virus or the protozoon”. The claim requires testing for infection by two types of bacteria. It is unclear what additional steps if any are required to avoid the use of transplantation material “infected with any bacterium, regardless of a type of the bacterium”. Thus the claims fails to clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claims 1 and 14 recite “a type of bacteria” and “types of bacteria”. The phrase “type” is indefinite. The specification fails to provide a definition of a “type” of bacteria. It is unclear if a “type” is intended to be a species, genus or class, whether a “type” of bacteria is intended to be a Gram-positive or Gram-negative type, or whether the phrase “type” is intended to be any type of bacteria.
Claims 2-10, 12-14 and 16 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 14 recites the limitation “avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium” and are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01.Claim 14 depends from claim 1 which recites the active steps ““performing a (i) genetic test for infection by pathogens comprising two or more types of bacteria, performing a (ii) genetic test for infection by pathogens comprising a virus or a protozoon-- wherein the (i) genetic test comprises using at least one primer that targets a common base sequence among at least two types of bacteria to perform a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test for the virus or the protozoon comprises using at least one primer that selectively binds to a nucleic acid sequence of at least one type of a virus or a protozoon to perform an identification of a type of the virus or the protozoon ---”. Claim 14 recites the additional active steps “evaluating a material which is detected to be infected with a pathogen comprising a bacterium by the performing the (i) genetic test, as unavailable for a xenotransplantation material product, evaluating a material which is not detected to be infected with a pathogen comprising a bacterium by the performing the genetic test, as available for a xenotransplantation material product”. The claim requires testing for infection by two types of bacteria. It is unclear what additional steps if any are required to avoid the use of transplantation material “infected with any bacterium, regardless of a type of the bacterium”. Thus the claims fails to clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim Rejections - 35 USC § 112(d)
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 14 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 14 recites the limitations “wherein the (i) genetic test performs a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test performs an identification of a type of the virus or the protozoon”. Independent claim 1, which claim 14 depends on, includes the limitation "performing a (i) genetic test for infection by pathogens comprising two or more types of bacteria --- wherein the (i) genetic test comprises using at least one primer that targets a common base sequence among at least two types of bacteria to perform a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test for the virus or the protozoon comprises using at least one primer-- to perform an identification of a type of the virus or the protozoon.” Claim 14 fails to further limit the recited limitations of claim 1. 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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 14 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. 35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claim is directed to the statutory category of a process.
Step 2A, Prong One
The claim is taken to be directed to a judicial exception (an abstract idea).
Claim 14 is directed to a method comprising “evaluating a material which is detected to be infected with a pathogen comprising a bacterium by the performing the (i) genetic test, as unavailable for a xenotransplantation material product, and evaluating a material which is not detected to be infected with a pathogen comprising a bacterium by the performing the genetic test, as available for a xenotransplantation material product”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the “evaluating” steps encompass the mental step of looking at genetic test results and making mental judgements.
The method of claim 14 further comprises “avoiding a use, as a transplantation material product, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the “avoiding” step encompasses the mental step of looking at genetic test results and making mental judgements.
2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 14 recites the additional elements: “wherein the (i) genetic test performs a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test performs an identification of a type of the virus or the protozoon.” These are not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method.
Since the claim does not amount to significantly more than the exception itself, or add anything markedly different from methods that are well known and established in the art, the claim is not patent eligible.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to “genetic tests” performed for detecting or identifying bacteria, viruses or protozoon are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
Furthermore, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activities in the life science arts when they are claimed in a merely generic manner or as insignificant extra-solution activity:
•Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir.2015)
• Amplifying and sequencing nucleic acid sequences, University of Utah Research
Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments against Claim Rejection - 35 U.S. C § 101
The response traverses the rejection on the grounds that the additional limitation “avoiding a use, as a transplantation material product, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium” recites a practical application. The response asserts that detecting the presence or absence of bacteria, without identifying the type of bacteria, and at the same time identifying the type of virus or protozoan, would not be considered routine, conventional, or well known; that the element of detecting the presence or absence of bacteria, without identifying the type of bacteria, is not routine, conventional, and well-understood; and that in testing for pathogen infection, identifying the species of the pathogen was routine, conventional, and well understood in the art. It was not routine, conventional, and well understood in the art to not identify the species. The response further asserts that there is a need for a method for testing for a plurality of types of pathogens that cause infection using the smallest number of tests as possible. The steps in the claimed method serve to reduce the number of tests compared to what is known in the art (p. 6).
Applicant's arguments have been fully considered but are not persuasive.
Regarding the assertion that the added limitation recites a practical application, it is instead a mental process, as set forth in the rejection above. Additional assertions, including that it was not routine, conventional or well-known at the time of filing to detect the presence or absence of bacteria without identifying the type, identifying a virus or protozoon at the same time, or identifying a pathogen without identifying the species, are also unpersuasive. These limitations were routine and conventional at the time of filing as demonstrated in the 103 rejection. Further the individual genetic tests were considered routine, conventional or well-known at the time of filing.
Regarding the assertion for the need for the claimed method of testing and the benefits of the method, these arguments are not directed to the claimed limitations but to the intended use and benefits of the claimed method, and cannot integrate a judicial exception.
The response also presents papers in support of their assertions.
Applicant's arguments have been fully considered but are not persuasive.
References cited by the applicant do not negate or overcome demonstration of techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
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 1-10 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Hartline et al. (Xenotransplantation panel for the detection of infectious agents in pigs. 2018. Xenotransplantation. 25: e12427, p. 1-15 and supplementary material wherein) in view of Klindworth et al. (Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies.2013. Nucleic Acids Research. (41) 1: e1-e11, and supplementary material wherein) and further in view of Center for Disease Control and Prevention, herein referred to as CDC (“U.S. Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation”. 2001. MWWR. 50(RR15); 1-46).
Regarding claim 1, Hartline teaches a method of detecting infectious agents using a screening panel in pigs to ensure safety for transplantation (xenotransplantation) (p. 1, Abstract). Hartline teaches performing qPCR (a genetic test) for infections by pathogens comprising ((ii) viruses (p. 1, Abstract and p. 3, Table 1). Hartline teaches using at least one primer that binds to at least one sequence of at least one type of virus (p. 3, cols. 1 and 2 and Table S1 (https://onlinelibrary.wiley.com/doi/10.1111/xen.12427)), satisfying the requirements of the (ii) genetic test for infection by pathogens comprising a virus.
Hartline also teaches performing qPCR (a genetic test) for infections by pathogens comprising (i) bacteria, including two groups (type) of bacteria (p. 1, Abstract and p. 3, Table 1), satisfying the requirements of the (i) genetic test for infection by pathogens comprising two or more types of bacteria.
Hartline does not teach the (i) genetic test comprises using at least one primer that targets a common base sequence among at least two types of bacteria to perform a detection of the presence or absence of bacteria without identifying a type of the bacteria. However, Hartline teaches adapting previously reported qPCR assay (i.e. primers) for inclusion in the common testing platform (p. 4, col. 1).
Klindworth teaches selecting primer pairs for PCR (a genetic test) of bacteria. Klindworth teaches the selection of primers that have high coverage (i.e. common base sequence targets) among all bacteria (i.e., at least two) (p. 1, Abstract and p 1, col 2). Klindworth teaches that primer pairs were investigated with respect to overall coverage and phylum spectrum (p. 1, col. 2), and that using suboptimal primers (i.e. primers with low coverage that do not target a common base sequence) can lead to under-representation or selection against species or groups of bacteria (p. 1, col. 2). Thus Klindworth teaches elements satisfying the requirements of the (i) genetic test.
Hartline teaches that the testing with the panel of infectious agents is essential to understand the spectrum of infectious agents in donor pigs to ensure safety for transplantation (p. 1, Abstract). Hartline further teaches that the panel provides investigators with excellent qualitative or quantitative information on each of the targets in the panel with the goal of understanding the infectious disease load in normal healthy animals and ensuring the safety of porcine tissues used in xenotransplantation research. Hartline states that the assays hold promise as part of screening program to identify suitable donor animals (p. 11, col. 2).
Hartline does not explicitly state avoiding the use of xenotransplantation material infected with any bacterium, regardless of a type of the bacterium.
CDC teaches viruses and bacteria are considered infectious agents in the context of xenotransplantation (p. 11, section 1.2). CDC teaches that candidate source animals (i.e. material) should be screened for the presence of infectious agents including bacteria and viruses (p. 26, section 3.5.1.1). CDC further teaches that All procured cells, tissues and organs intended for use in xenotransplantation should be as free of infectious agents as possible. The use of source animals in which infectious agents, have been identified should be avoided (p. 26, section 3.5.2). CDC thus teach elements satisfying the requirement avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth and CDC to arrive at the instantly claimed invention. The modification would have entailed using the PCR primers of Klindworth to perform the (i) genetic test of Hartline. One would have been motivated by the desire of Hartline to add targets to the assay (p. 13, col. 2) and ensure the safety of material for xenotransplantation. As taught by Hartline, the adaptation of existing primers was known at the time of filing and would have had a reasonable expectation of success. The modification would have further entailed screening for infectious agents as taught by the CDC to screen material for infectious agents avoid use of material in which infectious agents have been identified. In the context of material which is either safe or not safe for use, the presence of bacteria, of any type, would have been sufficient to exclude the material as stated by CDC. The universal primers of Klindworth would have provided a tool for screening a broad spectrum of infectious agents, a stated goal of Hartline (p. 2, col. 1). There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 2-4, neither Hartline nor CDC teach the common base sequence (for the (i) genetic test) is a sequence comprised in a conserved region of bacterial 16S rRNA (claim 12); the conserved region is a conserved region at least common to 16S rRNAs of Leptospira species, Mycoplasma species, Campylobacter species, Yersinia species, Escherichia species, and Salmonella species (claim 3); or the conserved region is regions between which V3 variable region and V4 variable regions only are sandwiched as variable regions (Claim 4).
Regarding claim 2, Klindworth teaches broad-range primers that target 16s ribosomal RNA genes (p. 1, Abstract). Klindworth states that 16s ribosomal RNA amplicon analysis is the standard approach for the cultivation independent investigation of microbial diversity (p. 1, Abstract).
Regarding claim 3, Klindworth teaches primers with coverage against Leptospira species, Mycoplasma species, Campylobacter species, Yersinia species, Escherichia species, and Salmonella species (Supplemental Table 4). Klindworth specifically teaches the preferred primer S-D-Bact-0341-b-S-17 (p 6, col 1) with coverage of at least 80% against each of Leptospira species, Mycoplasma species, Campylobacter species, Yersinia species, Escherichia species, and Salmonella species (Supplemental Table 4), thus satisfying the requirements of at least one primer that targets a conserved region in the claimed bacteria species.
Regarding claim 4, Klindworth teaches that the best primer pair for bacteria (S-D-Bact-0341-b-S-17/S-D-Bact-0785-a-A-21) in terms of domain and phylum coverage amplifies HV regions 3-4 (i.e. V3 and V4) (p6, col 1). Klindworth further teaches multiple primer pairs covering only the HV regions 3-4 (i.e. V3 and V4) (Supplemental Table 8).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth, and CDC to arrive at the instantly claimed invention. The modification would have entailed using the PCR primers targeting 16s ribosomal RNA of Klindworth in the method of Hartline. The ordinary artisan would have been motivated to use the primers of Klindworth for the added advantage of expanding the detection of a broad spectrum of infectious agents, a stated goal of Hartline (p. 2, col. 1) while using established targets for assaying bacteria. As taught by There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 5, neither Hartline nor CDC teach wherein one primer pair is used in the (i) genetic test.
Klindworth teaches individual primers that target two or more types of bacteria (Supplemental Table 4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth, and CDC to arrive at the instantly claimed invention. The modification would have entailed using the PCR primers of Klindworth in the method of Hartline. The ordinary artisan would have been motivated to use the primers of Klindworth for the added advantage of expanding the detection of a broad spectrum of infectious agents, a stated goal of Hartline (p. 2, col. 1). The primers of Klindworth would have maximized measurement of the presence of bacteria, while minimizing the effort required to adapt primers to the assay of Hartline (requiring optimization of only one set or primers), allowing Hartline to meet their goals of increasing targets and providing parallel evaluation of a large set of targets (p. 13, col. 2). One would have been motivated to select the known primer pairs taught by Klindworth to expand the number of assayed targets while minimizing the work or adapting primers that could be used with the common amplification protocol of Hartline. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 6, Hartline teaches performing qPCR on all targets in parallel (p3, col 1), using reagents arrayed in 96-well plates (p. 4, col 1, section 2.3), Hartline teaches performing qPCR on two types of Mycoplasma bacteria (i.e. the (i) genetic test) and 29 viruses (i.e., the (ii) genetic test).Hartline states that “qPCR was then performed on a QuantStudio 6 with a Fast block (Applied Biosystems) using an initial 20 seconds denaturation at 95°C, and 45 cycles of 95°C 1 second, 60°C 20 seconds.”, thus satisfying the requirement of “a PCR method with the same thermal cycle conditions using primers among which differences in melting temperature that are 15°C or less”.
Klindworth teaches selecting primer pairs for PCR of bacteria. Klindworth teaches the selection of primers that have high coverage (i.e. common base sequence targets) among all bacteria (i.e., at least two) (p. 1, Abstract and p 1, col 2). Klindworth further teaches evaluating 512 primer combinations (p. 2, col. 2 and Supplementary Table 8).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth, and CDC to arrive at the instantly claimed invention. The modification would have entailed using the PCR primers of Klindworth to perform the (i) genetic test of Hartline. One would have been motivated by the desire of Hartline targets to the assay (p. 13, col. 2) and ensure the safety of material for xenotransplantation. As taught by Hartline, the adaptation of existing primers was known at the time of filing and would have had a reasonable expectation of success. One would have been motivated to select primer pairs taught by Klindworth to expand the number of assayed targets while minimizing the work or adapting primers that could be used with the common amplification protocol of Hartline. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 7, Hartline teaches that infectious agents can transmit zoonotic infections (p. 2, col. 1).
Regarding claim 8, Hartline teaches testing more than 5 viruses by qPCR with specific primers (p. 3, Table 1 and Table S1).
Regarding claim 9, Hartline teaches the xenotransplantation product is pig-derived (p. 1, Abstract and p. 4, col. 2).
Regarding claim 10, Hartline teaches detecting viruses including Porcine cytomegalovirus (p. 3, Table 1).
Regarding claim 12, Hartline teaches that the goal of their method is to generate genetically engineered porcine organs for use in clinical trials to evaluate the potential of xenotransplantation (p. 2, col 1).
Regarding claim 13, Hartline teaches testing by qPCR (p. 1, Abstract and p. 3, Table 1).
Regarding claim 14, Hartline teaches that the testing assays can be a screening program to identify suitable donor animals and organs (p 11, col 2). Hartline also teaches that their data will help ensure the safety of tissue from animals for use in xenotransplantation studies (p 12, col 1).
Hartline further teaches testing 29 viruses by qPCR with specific primers, i.e. performing the (ii) genetic test to identify a type of virus (p. 3, Table 1 and Table S1).
Hartline teaches performing a genetic test (qPCR) for bacteria (p. 1, Abstract and p. 3, Table 1).
However, Hartline does not teach the (i) genetic test performs a detection of the presence or absence of bacteria without identifying a type of the bacteria.
Klindworth teaches detecting bacteria using PCR primers that have high coverage among all bacteria (i.e., the (i) genetic test detecting presence or absence of bacteria without identifying a type) (p. 1, Abstract and p 1, col 2).
Hartline also does not explicitly teach avoiding the use of xenotransplantation material infected with any bacterium, regardless of a type of the bacterium.
CDC teaches viruses and bacteria are considered infectious agents in the context of xenotransplantation (p. 11, section 1.2). CDC teaches that candidate source animals (i.e. material) should be screened for the presence of infectious agents including bacteria and viruses (p. 26, section 3.5.1.1). CDC further teaches that All procured cells, tissues and organs intended for use in xenotransplantation should be as free of infectious agents as possible. The use of source animals in which infectious agents, have been identified should be avoided (p. 26, section 3.5.2). CDC thus teach elements satisfying the requirement avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of a type of the bacterium.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth and CDC to arrive at the instantly claimed invention. The modification would have entailed using the PCR primers of Klindworth to perform the (i) genetic test of Hartline and evaluate the presence of bacteria using primers that have high coverage (i.e. report the presence of multiple bacteria). One would have been motivated by the desire of Hartline to increase targets to the assay (p. 13, col. 2) and ensure the safety of material for xenotransplantation in which bacteria were present. As taught by Hartline, the adaptation of existing primers was known at the time of filing and would have had a reasonable expectation of success. The modification would have further entailed screening for infectious agents as taught by the CDC to screen material for infectious agents avoid use of material in which infectious agents have been identified. The presence of bacteria, of any type, as measured by the primers of Klindworth, would have been sufficient to exclude the material as stated by CDC. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Hartline et al. (Xenotransplantation panel for the detection of infectious agents in pigs. 2018. Xenotransplantation. 25: e12427, p. 1-15 and supplementary material wherein) in view of Klindworth et al. (Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies.2013. Nucleic Acids Research. (41) 1: e1-e11) further in view of CDC (“U.S. Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation”. 2001. MWWR. 50(RR15); 1-46) as applied to claims 1-10 and 12-14 above, and further in view of Mansfield et al. (Japanese encephalitis virus infection, diagnosis and control in domestic animals. 2017. Veterinary Microbiology. 201: 85-92).
Regarding claim 16, neither Hartline nor Klindworth or CDC teach the virus comprises at least one type of virus selected from the group containing Geta virus, Japanese encephalitis virus, African swine fever virus, and Swine fever virus.
Mansfield teaches molecular methods for detecting Japanese encephalitis virus (p. 89, Table 1). Mansfield teaches Japanese encephalitis virus is a significant cause of neurological disease in humans and that the impact of Japanese encephalitis virus infection is particularly apparent in pigs (p. 85, Abstract). Mansfield states that it is critical to detect the virus and break the link to zoonotic transmission to the human population (p. 85, Abstract).
Mansfield further teaches primer sets for detecting Japanese encephalitis virus (p. 89, Table 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hartline, Klindworth, and CDC with Mansfield to arrive at the instantly claimed invention. The modification would have entailed additionally using the PCR primers of Mansfield in the method of Hartline. The ordinary artisan would have been motivated to use the primers of Klindworth for the added advantage of adding more targets to the set of agents described (p. 13, col. 2). One would have been further motivated to use the primers of Mansfield that target Japanese encephalitis virus because it poses a zoonotic risk similar to the already taught primers of Hartline, who was motivated to understand the spectrum of infectious agents in donor pigs. Furthermore, the method of Hartline taught adaptation of existing primers for inclusion with the panel of infectious agents. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Response to Arguments against Claim Rejection - 35 U.S. C § 103
The response asserts that the Examiner has apparently misconstrued Applicant's statements in the response dated 07/16/2025. To clarify, the response states the if Hartline desired to increase the number of detectable infectious agents, Hartline would be expected to prioritize using common primers targeting the conserved region for viruses, and provides no motivation for "the (i) genetic test performs a detection of the presence or absence of bacteria without identifying a type of the bacteria and the (ii) genetic test performs an identification of a type of the virus or the protozoan". (p. 8-9)
The Examiner recognizes and appreciates the clarification of the previous argument. However, Applicant's arguments have been fully considered but are not persuasive.
Hartline states the potential for adding additional targets to the panel (p. 13, col2. 2). Hartline (and CDC) recognize both bacteria and viruses as infectious targets to screen for. There is no reasonable expectation that the goal of increasing additional targets would require prioritizing using common primers targeting the conserved region for viruses. Hartline solves the problem of expanded targets by adapting primers to a common amplification protocol as described in the rejection to claim 6. Furthermore, universal (or common primers) for bacteria were well known in the art at the time of filing (as described in the 103 rejection above) and Hartline explicitly states that assays were performed as reported in the literature or adapted to the platform.
In addition, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The response asserts that Hartline is primarily concerned with viruses, and Hartline does not teach or suggest using common primers targeting the conserved regions of viruses. Hartline's disclosure relates to "common amplification protocol" and "common instrument", not common primers. Moreover, Hartline's detection, even as it pertains to bacteria, is also focused on specificity (p. 9).
Applicant's arguments have been fully considered but are not persuasive.
Hartline states that their concern is detection of infectious agents and therefore teach a test for both bacteria and viruses (known infectious agents of concern for xenotransplantation). It is acknowledged that Hartline does not teach or suggest common primers targeting the conserved regions of viruses. However, the instant claims do not require using common primers targeting the conserved regions of viruses.
Furthermore, the disclosure of a common amplification protocol does not preclude the use of common primers, and in fact he use of common primers as was known for bacteria would facilitate the use of a common protocol.
In regards to the assertion that Hartline’s detection of bacteria is focused on specificity, Hartline does not disclose a particular interest in restricting bacterial analyses to focus on specificity, but rather states a desire to add more (unspecified) targets to the set of agents.
The response cites the instant specification (paragraph [0005]) in support of the argument that there is a need for a method for testing for a plurality of types of pathogens that cause infection using the smallest number of tests as
possible. The response states that the steps in the claimed method serve to reduce the number of tests compared to what is known in the art by differentiating between the level of specificity for bacteria vs. that of viruses and protozoans. (p. 9)
Applicant's arguments have been fully considered but are not persuasive.
In response to applicant's argument that the steps in the claimed method serve to reduce the number of tests compared to what is known in the art by differentiating between the level of specificity for bacteria vs. that of viruses and protozoans, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
The response asserts there is no teaching or suggestion, even when the references are
combined, to reduce the number of tests by using at least one primer that targets a common base sequence among at least two types of bacteria to perform a detection of the presence or absence of bacteria without identifying a type of the bacteria.(p. 9)
The response asserts that the combined disclosures of the cited references provide no suggestion of performing a detection of the presence or absence of bacteria rather than identification of types of bacteria, and then avoiding a use, as a transplantation material, of any xenotransplantation material infected with any bacterium, regardless of the type of bacterium (p. 9).
Applicant’s arguments, regarding the combined disclosures lack of suggestion of performing a detection of the presence or absence of bacteria rather than identification of types of bacteria, than avoiding use of the material infected with any bacterium, regardless of the type of bacterium, with respect to the rejection(s) of claim(s) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection under 35 U.S.C. 103 are made over Hartline et al. (Xenotransplantation panel for the detection of infectious agents in pigs. 2018. Xenotransplantation. 25: e12427, p. 1-15 and supplementary material wherein) in view of Klindworth et al. (Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies.2013. Nucleic Acids Research. (41) 1: e1-e11, and supplementary material wherein) and further in view of Center for Disease Control and Prevention, herein referred to as CDC (“U.S. Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation”. 2001. MWWR. 50(RR15); 1-46).
Conclusion
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682