DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant's election with traverse of Group I and the species of IL1R2 in combination with genes involved in the innate immune system and particularly the combination of genes of S100A9, C3AR1, CD177 and CX3CR1 in the reply filed on 22 May 2026 is acknowledged. The traversal is on the ground(s) that “the subject matter of all claims and species is sufficiently related that a thorough search for the subject matter of any one Group of claims and species would encompass a search for the subject matter of the remaining claims and species. Thus, it is respectfully submitted that the search and examination of the entire application could be made without serious burden. “ This is not found persuasive because the claims have been restricted based upon 371 practice. As set forth in the restriction requirement 02 October 2025, the claimed inventions do not share a special technical linking feature because the technical feature of Group I was known in the art at the time the invention was made. Accordingly, restriction is proper since there is no special technical feature linking the recited groups, as would be necessary to fulfill the requirement for unity of invention. A showing of undue search burden is not required to establish that a restriction is proper in a 371 application. It is noted, however, that a search for the claims of Groups I and II would require undue burden because the searches would not be co-extensive with one another and because the examination would require a different analysis of the subject matter at least under 101 and with respect to prior art. Further, there is a significant burden to search and examine each of the genes and the hundreds of possible combinations of genes since each gene must be searched using different keywords and the searches are not co-extensive.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
3. Claims 1-18 are pending.
Claims 2-5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, 6-11 and 13-18 read on the elected invention and have been examined herein. Claim 14 has been examined to the extent that it reads on the elected species of the IL1R2 gene and claims 15-18 have been examined to the extent that they read on the elected species of the combination of each of the S100A9, C3AR1, CD177 and CX3CR1 genes. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
Priority
4. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in France on 06 July 2020. It is noted, however, that applicant has not filed a certified copy of the FR2007133 application as required by 37 CFR 1.55.
Note that as set forth in the Filing Receipt mailed on 11 April 2024, no access code has been provided for obtaining the certified copy of the FR document:
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Claim Interpretation
5. 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.
Claim Rejections - 35 USC § 101
6. 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.
Claims 1, 6-11 and 13-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between the level of expression of the recited genes and risk of incidence of a healthcare associated infection. That is, the claims are drawn to a method for determining the risk of incidence of a healthcare-associated infection in a patient and recite the single step of measuring the expression of the recited genes. The claims thereby recite the correlation between the expression of the genes and risk of a healthcare-associated infection. As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
Claim 11 recites “wherein the expression is normalized in relation to the expression of one or more housekeeping genes.” The claims thereby require performing a step of normalizing expression levels. Absent a clear definition for “normalizing” (normalized) in the specification or the claims, the broadest reasonable interpretation of the normalizing step is that this step may be accomplished by critical thinking processes. Such “normalizing” thereby encompasses processes that may be performed mentally and thus is an abstract idea.
To any extent that the normalizing step is intended to use a computer or software or pen and paper, the use of a generic computer or software program, or pen and paper, to implement an abstract idea does not itself impart patent eligibility.
As stated in MPEP 2106.04(a)(2) III “The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation” and that “Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer.”
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The additionally recited step of measuring expression levels is part of the data gathering process necessary to observe the judicial exception. This step does not practically apply the judicial exception.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the additionally recited step of measuring expression levels is recited at a high degree of generality and was well-known, routine and conventional in the prior art. This finding is evidenced by the teachings in the specification. For instance, the specification (para [0066]) states “In the case of an mRNA transcript, the detection may be performed by a direct method, by any process known to those skilled in the art which makes it possible to determine the presence of said transcript in the sample, or by indirect detection of the transcript after conversion of the latter into DNA, or after amplification of said transcript or after amplification of the DNA obtained after conversion of said transcript into DNA. Numerous methods exist for the detection of nucleic acids (see for example Kricka et al., Clinical Chemistry, 1999, no. 45(4), p.453-458; Relier G. H. et al., DNA Probes, 2nd Ed., Stockton Press, 1993, sections 5 and 6, p.173-249).” See also, para [0075] and [0077] of the specification.
See also MPEP 2106.05(d) II which states that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. 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);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. 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); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Note that while the claims recite detecting the expression of particular genes, the identity of the genes is part of the judicial exception and not something in addition to the recited judicial exceptions. The claims do not require using a particular non-conventional reagent, such as a particular, non-conventional probe or primer consisting of or comprising a specific nucleotide sequence so as to add something ‘significantly more’ to the recited judicial exceptions.
In Mayo v. Prometheus, the Supreme Court stated: "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(a) – Written Description
7. 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 1, 6-11 and 13-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a Written Description rejection.
In analyzing the claims for compliance with the written description requirements of 35 U.S.C. 112, first paragraph, a determination is made as to whether the specification contains a written description sufficient to show they had possession of the full scope of their claimed invention at the time the application was filed.
For claims drawn to a genus, MPEP § 2163 states:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").”
MPEP § 2163 goes on to state:
“An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004).”
In the present situation, the claims are drawn to methods that require detecting a “gene selected from the family of genes encoding molecules involved in the innate immune system.”
The specification does not provide a limiting definition for what constitutes “the family of genes” encoding for “molecules” involved (in any manner) with the innate immune system.
Rather, the specification only provides examples of genes (i.e., 9 genes) that fall within this genus of genes. That is, the specification (para [0036]) states:
“As examples of genes encoding molecules involved in the innate immune system, mention may be made of the following genes: GNLY, S100A9, C3AR1, ADGRE3, CD177, CX3CR1, IFIH1, OAS2, OAS3.”
The claims do not describe any other members of the genus of genes involved directly or indirectly in innate immunity.
The claims do not define the genes in terms of their complete structure or in terms of any other structural properties.
Yet, the claims encompass a potentially large genus of possible genes that are currently known or currently unknown which can act in any manner as part of the body’s response or defense against pathogens. The gene may be any gene that encodes for a protein that recognizes a pathogen or any cytokine, or any type of a signaling gene or any type of a defense gene. The description of the gene in terms of its function - i.e., “involved in” innate immunity does not adequately describe the complete structure or any other relevant identifying characteristics of the genes encompassed by the claims.
While methods are known in the art for detecting genes and determining their functional properties, possession may not be shown by merely describing how to obtain members of the claimed genus or how to identify their common structural features. See MPEP § 2163.
Thereby, a showing of how to potentially identify other genes which meet the limitation of a gene involved in innate immunity is not sufficient to establish that Applicants were in possession of the invention as broadly claimed.
Further, the specification does not disclose a clear structure-function relationship between the claimed genus of genes and the functional property of being involved in innate immunity.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Also, as noted in Vas-Cath Inc. v. Mahurkar (19 USPQ2d 1111, CAFC 1991), the Federal Circuit concluded that:
"...applicant must also convey, with reasonable clarity to those skilled in art, that applicant, as of filing date sought, was in possession of invention, with invention being, for purposes of "written description" inquiry, whatever is presently claimed."
With respect to the present invention, there is no record or description which would demonstrate conception of a representative number of genes within the very broadly claimed genus of genes involved in innate immunity. Therefore, the claims fail to meet the written description requirement because the claims encompass a significantly large genus of genes which are not described in the specification.
Double Patenting
8. 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 1, 6-11 and 13-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/014,885 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘885 are both inclusive of an in vitro or ex vivo method for determining a risk of incidence of a healthcare-associated infection, wherein the method comprises measuring the expression level of the IL-1R2 gene (a proinflammatory gene present on chromosome 2q11-q12) and the expression level of the S100A9, C3AR1, CD177 and CX3CR1 genes (i.e., genes in a family of genes involved in the innate immune system) in a sample from a patient. See in particular, claim 1 of ‘885 which recites measuring the level of expression of CD177 in sample from a patient, and claim 3 which recites further measuring in the sample the expression of the IL1R2, S100A9, C3AR1, and CX3CR1 genes.
Dependent claims 6-11 of ‘885 recite each of the limitations of present claims 6-11.
Regarding present claim 13, the claims of ‘885 necessarily require using a means of detection since the claims require performing a step of detecting the expression level of the genes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
9. Claims 1, 6-11 and 13-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-17 of copending Application No. 18/014,814 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘814 are both inclusive of an in vitro or ex vivo method for determining a risk of incidence of a healthcare-associated infection, wherein the method comprises measuring the expression level of the IL-1R2 gene (a proinflammatory gene present on chromosome 2q11-q12) and the expression level of the S100A9, C3AR1, CD177 and CX3CR1 genes (i.e., genes in a family of genes involved in the innate immune system) in a sample from a patient. See in particular, claim 1 of ‘814 which recites measuring the level of expression of at least one gene in a family of genes encoding molecules involved in the innate immune system, which genes are defined as S100A9, CD117, C3AR1, and CX3CR1 in claims 14-17; and claims 3-5 which depend from claim 1 and further require measuring the expression of IL1R2.
Dependent claims 6-11 of ‘814 recite each of the limitations of present claims 6-11.
Regarding present claim 13, the claims of ‘814 necessarily require using a means of detection since the claims require performing a step of detecting the expression level of the genes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.10. Claims 1, 6-11 and 13-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-11 and 13 of copending Application No. 18/014,878 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘878 are both inclusive of an in vitro or ex vivo method for determining a risk of incidence of a healthcare-associated infection, wherein the method comprises measuring the expression level of the IL-1R2 gene (a proinflammatory gene present on chromosome 2q11-q12) and the expression level of the S100A9, C3AR1, CD177 and CX3CR1 genes (i.e., genes in a family of genes involved in the innate immune system) in a sample from a patient. See in particular, claim 1 of ‘878 which recites measuring the level of expression of at least one gene (and thereby each of the genes) of IL1R2, S100A9, CD117, and C3AR1; and claims 3 and 4 which encompasses detecting the expression level of each of the IL1R2, S100A9, C3AR1, CD177 and CX3CR1 genes in a sample from the patient.
Dependent claims 6-11 of ‘878 recite each of the limitations of present claims 6-11.
Regarding present claim 13, the claims of ‘878 necessarily require using a means of detection since the claims require performing a step of detecting the expression level of the genes.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.11. Claims 1, 6-11 and 13-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 14-20 of copending Application No. 18/014,934 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘934 are both inclusive of a method comprising: measuring the expression level of the IL-1R2 gene (a proinflammatory gene present on chromosome 2q11-q12) and the expression level of the S100A9, C3AR1, CD177 and CX3CR1 genes (i.e., genes in a family of genes involved in the innate immune system) in a sample from a patient. See in particular, claim 1 of ‘934 which recites measuring the level of expression of at least one gene (and thereby each of the genes) of C3AR1 and CX3CR1; and claims 3 and 4 which depend from claim 1 of ‘934 and further comprise detecting the expression level of each of the IL1R2, S100A9, and CD177 genes in a sample from the patient. Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the method claimed in ‘934. Further, the method of ‘934 can also be used for the purpose of determining the risk of incidence of a healthcare-associated infection in a patient since the claims of ‘934 include the same measuring step as the present claims.
Dependent claims 6-11 of ‘934 recite each of the limitations of present claims 6-11.
Regarding present claim 13, the claims of ‘934 necessarily require using a means of detection since the claims require performing a step of detecting the expression level of the genes. The final intended use limitation of “for determining the risk of incidence of a healthcare-associated infection in a patient” does not materially distinguish the claimed method over the method claimed in ‘934.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.12. Claims 1, 6-11 and 13-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18/880,056 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘056 are both inclusive of a method comprising: measuring the expression level of the IL1R2 gene and the expression level of the S100A9, C3AR1, CD177 and CX3CR1 genes (i.e., genes in a family of genes involved in the innate immune system) in a sample from a patient. See in particular, claims 5 and 6 of ‘056 which depend from claim 1 therein and recite measuring the level of expression of the IL1R2 and CD177 genes and claim 12, which depends from claim 1 therein and recites measuring the expression level of the S100A9, CX3CR1 and C3AR1 genes in a sample from the patient. While the claims of ‘056 do not recite as a single embodiment a method that measures the expression of each of the S100A9, CX3CR1 and C3AR1 genes together with the IL1R2 and CD177 genes, since claims 5, 6 and 12 depend from claim 1 and have the intended use of determining the risk of death of a subject infected with a respiratory virus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods claimed in ‘056 so as to have measured the expression of each of the IL1R2, CD117, S100A9, CX3CR1, and C3AR1 genes in a sample from a patient. Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the method claimed in ‘056. Further, the method of ‘934 can also be used for the purpose of determining the risk of incidence of a healthcare-associated infection in a patient since the claims of ‘056 include the same measuring step as the present claims.
Regarding present claims 6-11, claims 8-11 of ‘056 recite each of the limitations of present claims 6-11.
Regarding present claim 13, the claims of ‘056 necessarily require using a means of detection since the claims require performing a step of detecting the expression level of the genes. The final intended use limitation of “for determining the risk of incidence of a healthcare-associated infection in a patient” does not materially distinguish the claimed method over the method claimed in ‘056.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 102
13. 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 6-11 and 13-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deirmengian, C. (US20060040301).
Deirmengian teaches an in vitro method comprising measuring the expression level of IL1R2 (i.e., a gene encoding a pro-inflammatory cytokine receptor located in the region of 2q11-2q12) and S100A9, C3AR1, CD177 (“PRV1” therein) and CX3CR1 (i.e., genes encoding molecules involved in the innate immune system) in a biological sample from a patient (see, e.g., para [0098-0099] and Tables I and II). Deirmengian exemplifies methods in which the expression level of IL1R2, PRV1/CD177, S100A9 and C3AR1 were increased in synovial fluid of patients having septic versus aseptic inflammation, while the expression level of CX3CR1was decreased in synovial fluid of patients having septic versus aseptic inflammation (Table II).
Deirmengian (para [0097]) characterizes the patients as follows:
‘Synovial fluid samples were aspirated from seven patients with acute S. aureus knee infections and five patients with acute gout of the knee. Some patients had total knee arthroplasties. All patients in both groups had approximately 90% neutrophils in the synovial fluid. All patients with S. aureus infection exhibited fever, acute arthritis, multiple positive S. aureus cultures, high CRP values (average, 22; range, 1.9-34), high ESR (average, 90; range, 39-125), and an elevated synovial WBC count (average, 90,000 cells/mm3; range, 27,000-183,000; average differential, 93% neutrophils).”
Thus, the patients have the property that they have come into contact with a healthcare provider or medical establishment or healthcare facility.
Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the method of Deirmengian. Further, the method of Deirmengian can also be used for the purpose of determining the risk of incidence of a healthcare-associated infection in a patient since the method includes the same measuring step as the present claims.
Regarding claim 6, Deirmengian teaches that the sample from the patient may be a blood sample (e.g., para [0013] and [0072]).
Regarding claim 7, Deirmengian teaches that the expression of the genes is determined by measuring the messenger RNA (mRNA) level (e.g., para [0041], [0079], [0099] and claim 4).
Regarding claims 8-10, Deirmengian teaches measuring gene expression by performing RT-PCR or hybridization (e.g., para [0016], [0036], [0038], [0054] and [0075]), which methods result in determining the sequence of the target nucleic acid and thereby are sequencing methods.
Regarding claim 11, Deirmengian teaches normalizing the gene expression / mRNA levels against control housekeeping genes (e.g., para [0045] and [0054]).
Regarding claim 13, the method of Deirmengian necessarily requires using a means of detection since the method requires performing a step of detecting the expression level of the genes. The final intended use limitation of “for determining the risk of incidence of a healthcare-associated infection in a patient” does not materially distinguish the claimed method over that of Deirmengian.14. Claim(s) 1, 6-7, 9, 10 and 13-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsalik (WO 2018/140256; cited in the IDS).
Tsalik teaches an in vitro method for determining mRNA expression profiles diagnostic of sepsis or diagnostic of risk of mortality from sepsis (e.g., p. 4, lines 11-16 and Example 2 beginning at p. 38). Tsalik reports that IL1R2 mRNA levels were up-regulated and CX3CR1 mRNA levels were down-regulated in nonsurvivors of sepsis as compared to survivors (Example 2, beginning at p. 38 and Supplementary Table 7).
In Example 3, Tsalik teaches methods comprising performing whole blood transcriptome (genome wide expression) profiling to detect patients with sepsis “including healthcare-associated infections such as ventilator associated pneumonia (VAP)” (p. 48-49). It is disclosed that patients were monitored for hospital acquired infections (HAI) and blood samples were obtained from patients at multiple time points. Tsalik (p. 49, line 34 to p. 50, line 3) states “We sought to identify host gene classifiers associated with development of ventilator associated pneumonia among intubated patients as compared with uninfected, intubated patients. After subjects were clinically and microbiologically categorized, we submitted peripheral blood samples from these patients for RNA sequencing and proteomic analysis according to our standard protocol.”
Since the method of Tsalik determines expression levels of all transcripts in the entire transcriptome in a blood sample from a patient in a hospital setting, the method of Tsalik is considered to be one that measures the expression level of each of the IL1R2, CD177, S100A9, CX3CR1 and C3AR1 genes in a blood sample from a patient, wherein the patient is one who has come into contact with a healthcare facility.
Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the method of Tsalik. Further, the method of Tsalik can also be used for the purpose of determining the risk of incidence of a healthcare-associated infection in a patient since the method includes the same measuring step as the present claims.
Regarding claim 6, as discussed above, the method of Tsalik is one that measures gene expression in whole blood samples from patients (Example 3, p. 48-49)
Regarding claim 7, the whole transcriptome sequencing method of Tsalik measures mRNA levels.
Regarding claim 10, the sequencing method of Tsalik necessarily involves performing a hybridization step.
Regarding claim 13, the method of Tsalik necessarily requires using a means of detection since the method requires performing a step of detecting the expression level of the genes. The final intended use limitation of “for determining the risk of incidence of a healthcare-associated infection in a patient” does not materially distinguish the claimed method over that of Tsalik.
15. A. Claim(s) 1, 6-11 and 13-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mommert (WO 2020002602; cited in the IDS).
B. Claim(s) 1, 6-11 and 13-18 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mommert (WO 2020002602; cited in the IDS).
C. Claim(s) 1, 6-11 and 13-18 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mommert (US 20210254165).
Regarding the rejections of “B” and “C”, the applied WO 2020002602 and US 20210254165 references each has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
U.S. Application 17/256,811 is the National Stage application of WO 2020002602. U.S. Application 17/256,811 published as US 20210254165. Citations below are with respect to US 20210254165, the specification of which is considered to be the English translation of WO 2020002602
Mommert teaches an in vitro or ex vivo method comprising measuring the expression level of IL1R2 (i.e., a gene encoding a pro-inflammatory cytokine receptor located in the region of 2q11-2q12) and S100A9, C3AR1, CD177, and CX3CR1 (i.e., genes encoding molecules involved in the innate immune system) in a biological sample from a patient (see, e.g., para [0040-0041] and [0073]).
Mommert (para [0018]) also teaches that “The term «patient» refers to an individual who has come into contact with a healthcare professional, such as a physician (for example, a general practitioner) or medical facility (for example, a hospital emergency or resuscitation service or intensive care unit).”Thus, the patients have the property that they have come into contact with a healthcare provider or medical establishment or healthcare facility.
Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the method of Mommert. Further, the method of Mommert can also be used for the purpose of determining the risk of incidence of a healthcare-associated infection in a patient since the method includes the same measuring step as the present claims. Note that Mommert teaches that the method disclosed therein is for determining the immunosuppression status of a patient and that immunodepressed patients are at a high risk of developing nosocomical infections - i.e., healthcare associated infections (para [0004-0005]).
Regarding claim 6, Mommert teaches that the sample from the patient may be a blood sample (e.g., para [0020]).
Regarding claim 7, Mommert teaches that the expression level is determined by measuring the messenger RNA (mRNA) level (e.g., para [0042]).
Regarding claims 8-10, Mommert teaches measuring the gene expression level by performing RT-PCR or hybridization or sequencing (e.g., para [0042-0045]).
Regarding claim 11, Mommert teaches normalizing the gene expression / mRNA levels against control housekeeping genes (e.g., para [0103], [0105] and [0072]]).
Regarding claim 13, the method of Mommert necessarily requires using a means of detection since the method requires performing a step of detecting the expression level of the genes. The final intended use limitation of “for determining the risk of incidence of a healthcare-associated infection in a patient” does not materially distinguish the claimed method over that of Mommert.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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