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. Election of group I, claims 1, 33, and 57-74, without traverse, in response filed 8/18/26 is acknowledged. In response to election of species - Applicant hereby elects the CD163 gene as the species without traverse.
2. Non-elected species are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
3. Priority
Applicant’s claim for domestic priority under 35 U.S.C. 119(e), filed 11/5/21 & 3/10/21, is acknowledged.
4. Claim Rejections: 35 USC § 112(a)
The following is a quotation 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.
Written Description
I. Claims 1, 33, and 57-74 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, 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.
Claims 1, 33, and 57-74 are directed to the following genus claims.
1. (Currently amended) A method of determining risk of preeclampsia in a pregnant subject, the method comprising: (a) obtaining cell-free ribonucleic acid (cfRNA) from a biological sample obtained from the pregnant subject; (b) quantifying expression levels of the cfRNA for one or more genes selected from the genes listed in Table 24, wherein the one or more genes comprise CD163 or NSRP1; (c) determining that the expression levels of the cfRNA for the one or more genes exhibit a change in expression associated with preeclampsia relative to reference expression levels and identifying whether the pregnant subject has an increased risk of preeclampsia, based at least in part on the determining in (c).
33. (Currently amended) The method of claim 1, wherein the biological sample is serum or plasma.
57. (New) The method of claim 1, wherein the one or more genes comprise CD163.
58. (New) The method of claim 1, wherein the one or more genes comprise NSRP1.
59. (New) The method of claim 1, wherein the one or more genes comprise two or more genes selected from the genes listed in Table 24.
60. (New) The method of claim 59, wherein the two or more genes comprise CD163 and NSRP1.
61. (New) The method of claim 59, wherein the one or more genes comprise three or more genes selected from the genes listed in Table 24.
62. (New) The method of claim 33, wherein the biological sample is the plasma.
63. (New) The method of claim 33, wherein the biological sample is the serum.
64. (New) The method of claim 1, wherein the biological sample is urine, saliva, or amniotic fluid.
65. (New) The method of claim 1, wherein the quantifying in (b) further comprises performing an amplification assay, a sequencing assay, or a hybridization assay.
66. (New) The method of claim 65, wherein the quantifying in (b) further comprises performing the amplification assay.
67. (New) The method of claim 66, wherein the amplification assay comprises quantitative real-time polymerase chain reaction (quantitative RT-PCR) or digital PCR.
68. (New) The method of claim 65, wherein the quantifying in (b) further comprises performing the sequencing assay.
69. (New) The method of claim 68, wherein the sequencing assay comprises massively parallel sequencing.
70. (New) The method of claim 1, further comprising performing reverse transcription on the cfRNA of (a) to produce complementary deoxyribonucleic acid (cDNA), and analyzing the cDNA to quantify the expression levels.
71. (New) The method of claim 1, wherein the preeclampsia comprises severe preeclampsia.
72. (New) The method of claim 1, further comprising identifying the pregnant subject as having the increased risk of the preeclampsia.
73. (New) The method of claim 1, further comprising identifying the pregnant subject as not having the increased risk of the preeclampsia.
74. (New) The method of claim 72, further comprising administering a treatment to the pregnant subject identified as having the increased risk of the preeclampsia.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“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., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“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.” MPEP 2163.
Furthermore, 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
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.
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) 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.
In the instant case, there is no structure associated with function with regard to the members of genus of one or more genes selected from the genes listed in Table 24, wherein the one or more genes comprise CD163 or NSRP1. Table 24 list several hundreds of genes with no apparent structure associated with the genes. This also includes elected genes comprising CD163 or NSRP1. Apart from the lack of structure of the elected genes it remains undescribed the unlimited number of genes of Table 24. Further, as per the specification the claims remain undescribed regarding a criteria set up by the method for evaluating the risk of preeclampsia in a pregnant subject to a wherein (1) the logarithm of change in expression of each of the quantified genes relative to a reference level obtained from control subjects not at risk of developing preeclampsia is at least ±0.2 (|log(FC)|≥0.2); (2) the coefficient of variation of each of the quantified genes relative to the reference level is at most 6; (3) the median expression across all samples is at least 5 counts per million reads (CPM); or (4) a combination of one or more of (1), (2), and (3); wherein an increased risk of preeclampsia is assigned to the pregnant subject when the risk score exceeds a threshold value.
No information, beyond the characterization of: A method of determining risk of preeclampsia in a pregnant subject, the method comprising: (a) obtaining cell-free ribonucleic acid (cfRNA) from a biological sample obtained from the pregnant subject; (b) quantifying expression levels of the cfRNA for one or more genes selected from the genes listed in Table 24, wherein the one or more genes consist of CD163 or NSRP1; (c) determining that the expression levels of the cfRNA for the one or more genes exhibit a change in expression associated with preeclampsia relative to reference expression levels and identifying whether the pregnant subject has an increased risk of preeclampsia, based at least in part on the determining in (c); wherein (1) the logarithm of change in expression of each of the quantified genes relative to a reference level obtained from control subjects not at risk of developing preeclampsia is at least ±0.2 (|log(FC)|≥0.2); (2) the coefficient of variation of each of the quantified genes relative to the reference level is at most 6; (3) the median expression across all samples is at least 5 counts per million reads (CPM); or (4) a combination of one or more of (1), (2), and (3); wherein an increased risk of preeclampsia is assigned to the pregnant subject when the risk score exceeds a threshold value.
Claims 65-70 further include amplification assay, a sequencing assay, or a hybridization assay; wherein no specific assay conditions are described. For example - Applicants have not sufficiently defined the conditions under which the hybridizations are to take place. Nucleic acid hybridization assays are extremely sensitive to the conditions in which they are performed, especially the overnight temperature of 50oC. The buffer composition, pH, temperature, length of time, salt concentrations, quality and source of template nucleic acid, are all variables which determine the reproducibility of a given hybridization experiment. Given the unpredictability of the art and the nature of hybridization experiments in general, it is not sufficient to merely cite hybridization without a clear and explicit recitation of the conditions associated with the hybridization. For example, the definition of stringency as it pertains to hybridization conditions is subject to interpretation and is different from laboratory to laboratory. Therefore, without a clear and explicit recitation of the conditions which were actually used by Applicants in isolating the claimed polynucleotides which hybridize to the disclosed sequences, the skilled artisan would not be able to practice the claimed invention and would not be reasonably apprised of the metes and bounds of the claimed invention.
Similarly, performing an amplification assay, a sequencing assay, a hybridization assay, wherein the amplification assay comprises quantitative real-time polymerase chain reaction (quantitative RT-PCR) or digital PCR; or further comprising performing reverse transcription on the cfRNA of (a) to produce complementary deoxyribonucleic acid (cDNA), and analyzing the cDNA to quantify the expression levels, without specific description in the claims, the skilled artisan would not be able to practice the claimed invention and would not be reasonably apprised of the metes and bounds of the non-descript claimed invention.
The genus of one or more genes selected from the genes listed in Table 24 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 one or more genes selected from the genes listed in Table 24, with specific structures having the associated function/activity, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”:
(a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Applicants’ are respectfully directed to the problems associated EC Classification in the section “Transferring the EC Classification enzyme to Non-Enzyme Comparisons”; pages 101-102 and Fig. 2a)-b), highlighting the structural and functional heterogeneity based on EC Classification numbers; as the stereo-specificity, substrate-specificity and catalytic properties vary widely.
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also 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 (page 309, paragraph 4), 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 three protein functions, 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 (page 312, paragraph 5), 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 (page 313, paragraph 4), 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 (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity.
As stated above, no information beyond the characterization of: beyond the characterization of: A method of determining risk of preeclampsia in a pregnant subject, the method comprising: (a) obtaining cell-free ribonucleic acid (cfRNA) from a biological sample obtained from the pregnant subject; (b) quantifying expression levels of the cfRNA for one or more genes selected from the genes listed in Table 24, wherein the one or more genes consist of CD163 or NSRP1; (c) determining that the expression levels of the cfRNA for the one or more genes exhibit a change in expression associated with preeclampsia relative to reference expression levels and identifying whether the pregnant subject has an increased risk of preeclampsia, based at least in part on the determining in (c); wherein (1) the logarithm of change in expression of each of the quantified genes relative to a reference level obtained from control subjects not at risk of developing preeclampsia is at least ±0.2 (|log(FC)|≥0.2); (2) the coefficient of variation of each of the quantified genes relative to the reference level is at most 6; (3) the median expression across all samples is at least 5 counts per million reads (CPM); or (4) a combination of one or more of (1), (2), and (3); wherein an increased risk of preeclampsia is assigned to the pregnant subject when the risk score exceeds a threshold value.
As the claimed genera/genus of genes having widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Further, as per the specification the claims remain undescribed regarding a criteria set up by the method for evaluating the risk of preeclampsia in a pregnant subject with a clear description of the step/criteria/indices required by the method. Also describing the Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are 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.
5. Claim Rejections - 35 USC § 112 (second paragraph)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 33, and 57-74 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 pre-AIA the applicant regards as the invention.
Claims 1 & 59 & 61 recite – Table 24 which includes several hundreds of genes
"Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table 'is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.' Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)" (MPEP 2173.05(s)).
Applications in TC 1600 commonly include tables with large numbers of genes, proteins, small molecule biomarkers, diseases, acceptable excipients, etc. Claims cannot refer back to these tables in the specification; e.g., "wherein the biomarkers are selected from the group consisting of those listed in Table 4" or "wherein the cancer is one of those listed in Table 3." Claims such as these should be rejected under §112(b), and Applicants instructed to copy the table contents into the claim itself. There is no limit to the length of a claim. If the subject matter can be listed in the specification, that list can be copied and pasted into a claim.
An example of subject matter that can be listed in the specification, and where reference to an external figure is permissible, would be "A cocrystal of substances A and B, having an x-ray diffraction pattern as illustrated in Fig. 1." An x-ray diffraction pattern cannot feasibly be described using words.
Claims 33, and 57-58, 60 & 62-74 are included in the rejection for failing to correct the defect present in the base claim(s).
6. No claim is allowed.
7. 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
Prosecution Insights