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 .
DETAILED ACTION
1. Applicant’s election of Group I (claims 1-12 & 16) in the reply filed on 7/23/26 is acknowledged. Upon reconsideration of the restriction requirement mailed 5/12/26, claims 13-15 drawn to - A method of diagnosing a bacterial infection of a patient in vitro, comprising subjecting a sample of the patient to be diagnosed to the system of claim 1, wherein the sample is pre-treated to remove contaminants therefrom, and subsequently subjected to a reaction with the enzyme, and a bacterial infection is diagnosed based on the detected level of D-lactate are rejoined and the restriction requirement as set forth in the Office action mailed on 5/12/26 is hereby withdrawn.
2. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
3. Claims 1-16 are under consideration in this Office Action.
4. Priority
Receipt is acknowledged of papers (foreign priority filed 12/13/21) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
5. Drawings filed 6/11/24 are acknowledged.
6. IDS filed 6/11/24 is acknowledged.
7. Abstract
*This application does not contain an abstract of the disclosure as required by 37 CFR 1.72(b). An abstract on a separate sheet is required.
*The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words [in length since the space provided for the abstract on the computer tape by the printer is limited]. The form and legal phraseology often used in patent claims, such as "means" and "said", should be avoided in the abstract. The abstract should sufficiently describe the disclosure to assist readers in deciding whether there is a need for consulting the full patent text for details. MPEP 608.01(b).
Line 2 of the abstract recite legal phraseology “said enzyme” which must be deleted, and replaced with “the enzyme”.
8. 35 U.S.C. § 112, first paragraph (Written Description)
Claims 1-16 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.
The claimed invention is directed to the following genus claims:
1. (Previously Presented): A system for detecting bacterial infection in a patient sample in vitro, comprising:
a stereospecific enzyme having D-lactate oxidizing activity,
a detector configured to detect a reaction product of said enzyme, and
a separator configured to remove contaminants by filtration, centrifugation or enzymatic
catalysis.
2. (Original): The system according to claim 1, further comprising a means for removing
contaminants from the sample, wherein said means is preferably adapted to removing
contaminants by filtration, centrifugation, and/or enzymatic catalysis.
3. (Previously Presented): The system according to claim 1, wherein the system
comprises a colorimetric assay or an electrochemical sensor.
4. (Previously Presented): The system according to claim 1 which is configured to be
used at the point of care.
5. (Previously Presented): The system according to claim 1, wherein the means for
detecting a reaction product of the enzyme comprises a compound that is directly converted to a detectable substance by the action of the enzyme.
6. (Original): The system according to claim 5, wherein the compound is a tetrazolium
dye, preferably MTT.
7. (Previously Presented): The system according to claim 1, wherein the system is
configured for the analysis of a sample in a dip stick or flow-through format.
8. (Previously Presented): The system according to claim 1, wherein the system further
comprises a cutoff reagent, wherein preferably said cutoff reagent is suitable for accepting
electrons from the enzyme or the enzyme's cofactor.
9. (Previously Presented): The system according to claim 1, further comprising a
buffering agent configured to maintain a pH value of the combined sample reagents of 7.5 to 9.5 during use.
10. (Previously Presented): The system according to claim 1, wherein the enzyme is (i)
provided in solution or (ii) coupled to a solid support, preferably an electrode or a cellulose-based membrane.
11. (Previously Presented): The system according to claim 1, wherein the system is
adapted for discriminating a D-lactate concentration of a first concentration and a second
concentration by a binary readout.
12. (Previously Presented): The system according to claim 1, wherein said enzyme is
selected from the group consisting of:
(a) a protein having D-lactate oxidizing activity that is independent of NAD and/or
NADP;
(b) a protein having D-lactate oxidizing activity isolated from a deltaproteobacterial
species;
(c) a protein comprising SEQ ID NO: 1;
(d) a protein comprising a sequence having at least 85%, 90% or at least 95% sequence
identity to SEQ ID NO: 1; and,
(e) a functional fragment of (a), (b), (c) or (d).
13. (reconsidered in this Office Action (OA)): A method of diagnosing a bacterial infection of a patient in vitro, comprising subjecting a sample of the patient to be diagnosed to the system of claim 1, wherein the sample is pre-treated to remove contaminants therefrom, and subsequently subjected to a reaction with the enzyme, and a bacterial infection is diagnosed based on the detected level of D-lactate.
14. (reconsidered in this OA): The method according to claim 13, wherein a bacterial infection is diagnosed when the level of D-lactate in the sample is at least 0.04 to 0.06 mM.
15. (reconsidered in this OA): The method according to claim 13, wherein said sample is selected from the group consisting of synovial fluid, cerebrospinal fluid, urine, and blood.
16. (Previously Presented): The system of claim 1, wherein the separator is configured to
remove contaminants prior to the detector detecting the reaction product of the enzyme.
The claims 1-11 &13-16 are described by functional limitations only and are devoid of a reference structure for the claimed protein comprising SEQ ID NO: 1 as in claim 12. The claimed invention encompasses a genus of protein or D-lactate dehydrogenase having D-lactate oxidizing activity not adequately described.
The instant specification describes – “A system for detecting bacterial infection in a patient sample in vitro, comprising:
a stereospecific enzyme of SEQ ID NO: 1 having D-lactate oxidizing activity,
a detector configured to detect a reaction product of said enzyme, and
a separator configured to remove contaminants by filtration, centrifugation or enzymatic
catalysis; or A method of diagnosing a bacterial infection of a patient in vitro, comprising subjecting a sample of the patient to be diagnosed to the system of claim 1, wherein the sample is pre-treated to remove contaminants therefrom, and subsequently subjected to a reaction with the enzyme, and a bacterial infection is diagnosed based on the detected level of D-lactate; wherein said sample is selected from the group consisting of synovial fluid, cerebrospinal fluid, urine, and blood; and wherein a bacterial infection is diagnosed when the level of D-lactate in the sample is at least 0.04 to 0.06 mM.
The instant specification does not describe clearly describe the system/method for detecting bacterial infection in a patient sample in vitro using any D-lactate oxidizing enzyme or that isolated from a deltaproteobacterial species; (c) a protein comprising SEQ ID NO. 1; (d) a protein comprising a sequence having at least 85%, 90% or at least 95% sequence identity to SEQ ID NO. 1; and, (e) a functional fragment of (a), (b), (c) or (d), which requires fragment of SEQ ID NO: 1 of any length and having the required function or a protein sequence of SEQ ID NO: 1 with varying sequence homologies of 85%, 90% or 95% as no variants are described or taught.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe aninvention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what isclaimed."). Thus, an applicant complies with the written description requirement "bydescribing the invention, with all its claimed limitations, not that which makes it obvious,"and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966."Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents" of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case is discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
Moreover, Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir.1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
9. Claims 1-16 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.
Claims 1-16 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.
The omitted steps are: “A system for detecting bacterial infection in a patient sample in vitro, comprising: a stereospecific enzyme of SEQ ID NO: 1 having D-lactate oxidizing activity, a detector configured to detect a reaction product of said enzyme, and
a separator configured to remove contaminants by filtration, centrifugation or enzymatic
catalysis; wherein said sample is selected from the group consisting of synovial fluid, cerebrospinal fluid, urine, and blood; and wherein a bacterial infection is diagnosed when the level of D-lactate in the sample is at least 0.04 to 0.06 mM;
or A method of diagnosing a bacterial infection of a patient in vitro, comprising subjecting a sample of the patient to be diagnosed to the system of claim 1, wherein the sample is pre-treated to remove contaminants therefrom, and subsequently subjected to a reaction with the enzyme, and a bacterial infection is diagnosed based on the detected level of D-lactate; wherein said sample is selected from the group consisting of synovial fluid, cerebrospinal fluid, urine, and blood; and wherein a bacterial infection is diagnosed when the level of D-lactate in the sample is at least 0.04 to 0.06 mM. (The omitted steps are bolded and underlined).
10. Claims 1-16 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 “A system for detecting bacterial infection in a patient sample in vitro, comprising: a stereospecific enzyme having D-lactate oxidizing activity, a detector configured to detect a reaction product of said enzyme, and a separator configured to remove contaminants by filtration, centrifugation or enzymatic catalysis.”
The recitation of a step “and a separator configured to remove contaminants by filtration, centrifugation or enzymatic catalysis”, follows all the critical steps such as enzyme sampling, D-lactate oxidizing activity and detection steps are completed – which is very confusing and indefinite. The sample to the tested must be made free of contaminants as a first step.
Claims 2-16 are included in the rejections for failing to correct the defect present in the base claim 1.
11. Claims 2, 6, 8 & 10 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.
The use of the expressions “preferably” attempts to give both broad and narrow meaning to the scope of the above claims. These claims are unclear.
12. Claim Rejection – 4th paragraph
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 2 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 2 depends on claim 1, and recites “..further comprising a means for removing contaminants from the sample, wherein said means is preferably adapted to removing contaminants by filtration, centrifugation, and/or enzymatic catalysis, a reference to previous claims but fail to further limit the subject matter claimed. Claim 2 is rejected under 35 U.S.C. § 112. 4th paragraph.
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.
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) 1-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/221847 A1.
WO 2020/221847 A1, 5 November 2020 teaches a method for diagnosing an infectious disease, for example infections of prosthetic joints, involving determining the level of D-lactate in a sample of a subject exhibiting clinical symptoms of and/or suspected of having an infection, wherein the level of D-lactate is indicative of the presence of an infectious disease. The level of D-lactate in sample is determined using an electrochemical biosensor comprising a D-lactate dehydrogenase (D-LDH). Said biosensor may be in the form of a test strip (p. 5, 11). Cut-off values are also determined (p. 8). A buffer solution with a pH of about 7.5 - 9.5 is preferred, while a pH of about 8 - 9 is more preferred and a pH of 8.5 is particularly preferred as it was shown that D-LDH works very effectively in detecting D-lactate in the context of an electrochemical sensing system at pH 8.5 (p. 9). A kit comprising the same is also disclosed (p. 10). WO 2020/221847 A1 also mentions the determination of synovial fluid D-lactate spectrophotometrically from the optical density of the prepared sample using a commercial kit. The determination is based on a spectrophotometric method with a standard microplate absorbance reader at 570 nm, requiring 50 µI of synovial fluid. In the assay D-LDH catalyzes the oxidation of D-lactic acid to pyruvate, along with the concomitant reduction of nicotinamide adenine dinucleotide (NAO+) to NADH. NADH reacts with the fluorescent substrate to yield coloration of the mixture (p. 33). Removal of contaminants by filtration, centrifugation, and/or enzymatic catalysis are basic requirements for carrying out any assay/method/system and is given no patentable weight. Further, the claim(s) do not specify where from the contaminants are removed by filtration, centrifugation or enzymatic catalysis.
14. No claim is allowed.
15. US-20220206009-A1 is cited as an relevant reference – but currently not used in any rejection.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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