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
Application Status
This application is a DIV of US patent application 16/978,464, filed on 05/16/2024.
Claims 80-84, 86-91 and 92 are currently pending in this patent application.
The preliminary amendment filed on 09/04/2025, canceling claims 85, and adding new claim 92 is acknowledged.
Election/Restriction
Applicant's election with traverse of species 300 femtogram/mL in the response filed on 09/04/2025 is acknowledged.
Arguments: Applicants argue that pursuant to 37 C.F.R. §§ 1.111 and 1.143, Applicants hereby traverse the Examiner's requirement for restriction and request reconsideration thereof in view of the following remarks. An Examiner's authority to require restriction is defined and limited by statute: If two or more independent and distinct inventions are claimed in one application, the Commissioner may require the application to be restricted to one of the inventions. 35 U.S.C. § 121, first sentence (emphasis added). The implementing regulations of the Patent and Trademark Office include the mandate that restriction is appropriate only in cases presenting inventions which are both independent and distinct, 37 C.F.R. §§1.141-142. Without a showing of independence and distinctness, a restriction requirement is unauthorized. In the present application, the claims which the Examiner has grouped separately are not "independent and distinct" so as to justify the restriction requirement. The claimed assay can measure GFAP at a Lower Limit of Detection (LLOD) of less than about 500 femtograms/mL, such as about 0.1 to about 500 femtogram/mL, or less than about 300 fg/mL. such as about 150 fg/mL, and preferably below 100 femtogram/mL, preferably below 50 femtogram/mL, preferably below 25 femtogram/mL, preferably below 10 femtogram/mL. The LLOD species are within a close range and merely different aspects of a single invention. The courts have recognized that it is in the public interest to permit applicants to claim several aspects of their invention together in one application, as the applicants have done herein. The CCPA has observed: We believe the constitutional purpose of the patent system is promoted by encouraging applicants to claim, and therefore to describe in the manner required by 35 U.S.C. §112 all aspects as to what they regard as their invention, regardless of the number of statutory classes involved. In re Kuehl, 456 F.2d 658, 666, 117 U.S.P.Q. 250, 256 (CCPA 1973). This interest is consistent with the practical reality that a sufficiently detailed disclosure supporting claims to one aspect of an invention customarily is sufficient to support claims in the same application to other aspects of the invention. Furthermore, Applicant respectfully submits that reliance on the supposed classification of the species of the pending claims does not establish independence and distinctness. The classification system has no statutory recognition as evidence of whether inventions are independent and distinct. The classification system is instead an aid in finding and searching for patents. The classification system is also an unreliable basis for requiring restriction between species to the various aspects of applicants' unitary invention, because the system exhibits considerable overlap in technical definitions. In particular, the definitions of classes and subclasses in the classification system do not prevent the Examiner from basing patentability decisions, as to species, on patent references found in the classes or subclass(es) with which he associated another species. Moreover, the classification system is a poor basis for requiring restriction between related aspects of an invention because classifications and definitions change over time. Thus, a classification that might have seemed to support restriction at a given time could change, thereby casting a shadow over the propriety of the restriction requirement later on during the term of the patents issuing from parent and divisional applications. Indeed, classifications seem largely to change in response to considerations of administrative convenience, and often in response to nothing more than growth in the number of patents in a given class or subclass. These considerations have nothing to do with whether the subject matter of patents assigned to different classifications is "independent and distinct" as those terms are used in 35 U.S.C. §121, which fact proves that basing restriction requirements on the classification system is improper. Notably, no classes or subclasses are identified by the Examiner, only a bald allegation that "the species require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search..." Applicant respectfully suggests that in view of the continued increase of official fees and the potential limitation of an applicant's financial resources, a practice which arbitrarily imposes restriction requirements may become prohibitive and thereby contravene the constitutional purpose to promote and encourage the progress of science and the useful arts. All these considerations indicate that the imposition of a restriction requirement with inadequate authority can lead to situations in which an applicant's legitimate patent rights are exposed to uncertainty and even extinguished. Accordingly, to protect a patentee's rights and to serve the public interest in the legitimacy of issued patents, Applicant respectfully urges the Examiner not to require restriction in cases such as the present application wherein various aspects in a unitary invention are claimed. Finally, Applicant respectfully submits that a determination to make the pending restriction requirement final must evidence the patentable distinctness of the species, one from the other, as presented by the Examiner.
Response: The Examiner is hereby stating that the species election of Restriction requirement is hereby withdrawn, and all the .
The requirement is still deemed proper and is therefore made FINAL.
Claims 80-84, 86-91 and 92 are present for examination.
Priority
Acknowledgement is made of applicants claim for priority of US patent application 16/978,464, filed on 09/04/2020, and US Provisional applications 62/640,220, filed on 03/08/2018, 62/666,328, filed on 05/03/2018, and 62/672,263, filed on 05/16/2018.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 10/24/2024, 09/30/2024, and 05/06/2024 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner. The signed copies of 1449 are enclosed herewith.
Drawings
Drawings submitted on 05/16/2024 are objected by the Examiner because the figures are NOT legible. Appropriate correction is required.
Claim Objections
Claims 80-82, 87-91 and 92 are objected to in the recitation “GFAP”; as abbreviations should not be used without at least once fully setting forth what they are used for. Appropriate correction is required.
Claim 82 is objected to in the recitation “MSD”; as abbreviations should not be used without at least once fully setting forth what they are used for. Appropriate correction is required.
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.
Claims 86-91 and 92 are rejected under 112(b) indefinite because each of the steps of the assay method contains multiple sentences with multiple periods in claim 86, such as “a.” “b.” or “c.”. which can be changed to (a) or a) without any period in the middle of the claim. According to MPEP- Claims must be drafted as a single sentence with a single period. Clarification and correction are required.
Claim Rejections - 35 USC § 112(a)
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.
A. Written Description
Claims 80-84, 86-91 and 92 are rejected under 35 U.S.C. 112(a), as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claim 80 is interpreted under Broadest Reasonable Interpretation (BRI), is directed to encompass: an ultrasensitive assay for detecting GFAP (glial fibrillary acidic protein) in a sample from a subject, comprising, in one or more vials, containers, or compartments: a. a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; and b. a detection reagent for GFAP that is linked to a nucleic acid probe, wherein the nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500 femtogram/mL.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “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”. As indicated in MPEP § 2163, 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, reduction to drawings, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Claims are directed to an ultrasensitive assay for detecting any GFAP (glial fibrillary acidic protein) derived from any sources having no structural feature in any sample from any subject, comprising, in one or more vials, containers, or compartments: a. a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; and b. a detection reagent for GFAP that is linked to a nucleic acid probe, wherein the nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500 femtogram/ml, i.e. claimed GFAP proteins, which are derived from many unknown sources as well as many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, i.e. No Structure-Function Correlation, which is required for fulfilling the Written Description requirement.
As discussed in the written description guidelines 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, reduction to drawings, 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 applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, Claims are drawn to an ultrasensitive assay for detecting any GFAP (glial fibrillary acidic protein) derived from any sources having no structural feature in any sample from any subject, comprising, in one or more vials, containers, or compartments: a. a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; and b. a detection reagent for GFAP that is linked to a nucleic acid probe, wherein the nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500 femtogram/ml, i.e. claimed GFAP proteins, which are derived from many unknown sources as well as many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of few GFAP proteins has been provided, which would indicate that applicants had possession of the claimed genus.
Furthermore, the genus of genes and encoded polypeptides and functional homologs or variants required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides and encoding polynucleotides are adequately described by the disclosure of the structures of prior art, i.e., genes associated with the production of amino acids, since one could use structural homology to isolate those polypeptides and the encoding polynucleotide recited in the claims. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer, it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given few GFAP protein functions with detection, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions, in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity, although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (see, whole document). This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated, no information, beyond the characterization of few GFAP proteins has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the GFAP proteins within the scope of the claimed genus. The genus of polypeptides claimed is a large variable genus including many GFAP proteins, with many mutants, variants and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated GFAP proteins are encompassed within the scope of these claims. The specification teaches the structure of only few representative species of such proteins. Moreover, the specification fails to describe any other representative species by any identifying characteristics or properties other than the functionality of encoding the polypeptide having ability of producing amino acids in said genetically modified microorganism cells. Given this lack of description of representative species encompassed by the genus of polypeptides of the claim, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Double Patenting Rejection
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. See 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); and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 80-84, and 86-92 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-16 of U.S. Patent No.US12339275B2, granted on 06/24/2025.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim, because the examined claim is either anticipated by, or would have been obvious over the reference claim. 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).
Although the conflicting claims are not identical, they are not patentably distinct from each other because each claim set recites the same invention. Claims 80-92 are drawn to an ultrasensitive assay for detecting GFAP in a sample from a subject, comprising, in one or more vials, containers, or compartments: a. a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; and b. a detection reagent for GFAP that is linked to a nucleic acid probe, wherein the nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500 femtogram/mL, wherein said assay is configured to detect GFAP at a level below 300-10 femtogram/mL, wherein said GFAP detection is analyzed on an MSD platform, which is configured to perform a multiplexed assay, which is configured to be conducted in a single assay chamber.
Claims 1-16 of US patent 12339275 B2 disclose an assay configured to determine or detect the presence or level of two or more biomarkers in a sample from a subject, wherein said two or more biomarkers comprise apolipoprotein 4 (APOE4) and glial fibrillary acidic protein (GFAP) and wherein said assay is configured to detect GFAP at a Lower Limit of Detection (LLOD) of 0.1 to 500 femtogram/mL, which is configured to assess traumatic brain injury (TBI), which is configured to determine the presence or level of APOE4 and the level of GFAP, wherein the GFAP detection is analyzed on an Meso Scale Discovery (MSD) platform, which is configured to perform a multiplexed assay, which is configured to be conducted in a single assay chamber, which comprising, in one or more vials, containers, or compartments (a) a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; (b) a first detection reagent for GFAP that is linked to a first nucleic acid probe, wherein the first nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; and (c) a second detection reagent for GFAP that is linked to a second nucleic acid probe; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500-10 femtogram/mL wherein said assay is two singleplex assays.
The above indicated claims of the reference patents while not totally identical to the instant claims, are indeed an ultrasensitive assay for detecting GFAP in a sample from a subject, and multiplex as claimed in the instant claims. The portion of the specification of the claims in the reference patents, while drawn to the actual product produced by a method, as claims in the instant application, includes several embodiments that would anticipate the invention claimed in the instant application. Claims of the instant application listed above cannot be considered patentably distinct over claims 1-16 of the reference patents when there are specifically recited embodiments that would either anticipate to claims 80-84, and 86-92 of the instant application or alternatively render them obvious. Alternatively, claims 80-92 cannot be considered patentably distinct over claims 1-16 of the reference patents when there is specifically disclosed embodiment in the reference patent that falls within the scope of claims 80-84, and 86-92 of the instant application, i.e. there is substantially overlapping scope between the claimed invention and the teachings of the reference. One having ordinary skill in the art would have been motivated to do this because that embodiment is disclosed as being a preferred embodiment within the claims 1-16 of US patent 12339275 B2.
Conclusion
Status of the claims:
Claims 80-84, 86-91 and 92 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656a
80. An ultrasensitive assay for detecting GFAP in a sample from a subject, comprising, in one or more vials, containers, or compartments: a. a surface comprising (i) a capture reagent for GFAP, said capture reagent bound to the surface, and (ii) an anchoring reagent bound to an anchoring oligonucleotide sequence, said anchoring reagent bound to the surface; and b. a detection reagent for GFAP that is linked to a nucleic acid probe, wherein the nucleic acid probe comprises an extended sequence that is complementary to the anchoring oligonucleotide sequence bound to the anchoring reagent; wherein the assay is combined to form a proximity-based detection system, and the assay is configured to detect GFAP at a level below 500 femtogram/mL, wherein said assay is configured to detect GFAP at a level below 300 femtogram/mL, wherein said GFAP detection is analyzed on an MSD platform, which is configured to perform a multiplexed assay, and which is also configured to be conducted in a single assay chamber, wherein said assay is configured to detect GFAP at a level below 300-10 femtogram/mL.