DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/18/2025 has been entered.
Status of Claims
Currently, claims 7 and 17-29 are pending in the instant application. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant Application. This action is Non-FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Improper Markush Group
Claims 7 and 17-29 are rejected under the judicially approved “improper Markush grouping” doctrine. (See Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, page 7166). This rejection is appropriate when claims contain an improper grouping of alternatively useable species. See In re Harnisch, 631 F. 2d 716, 719-20 (CCPA 1980).
The claims are directed to a kit that comprises oligonucleotides comprising probes that target at least ten different chromosomal regions set forth in the claimed table. Therefore, the claims are directed to alternative combinations of oligonucleotides. A Markush claim contains an ‘improper Markush grouping’ if : (1) the species of the Markush group do not share a ‘single structural similarity,’ or (2) the species do not share a common use.
MPEP 803.02 provides guidance on the analysis of a proper Markush group. The MPEP sets forth:
Since the decisions in In re Weber, 580 F.2d 455, 198 USPQ 328 (CCPA 1978) and In re Haas, 580 F.2d 461, 198 USPQ 334 (CCPA 1978), it is improper for the Office to refuse to examine that which applicants regard as their invention, unless the subject matter in a claim lacks unity of invention. In re Harnisch, 631 F.2d 716, 206 USPQ 300 (CCPA 1980); and Ex parte Hozumi, 3 USPQ2d 1059 (Bd. Pat. App. & Int. 1984). Broadly, unity of invention exists where compounds included within a Markush group (1) share a common utility, and (2) share a substantial structural feature essential to that utility.
In the instant situation, the specification teaches identification of circulating nucleic acid biomarkers that were found in prostate cancer subjects. Regions within human chromosomes that comprise these circulating nucleic acids are set forth in the table in claim 7. However, each of the chromosome regions are from different human chromosomes, each anywhere from tens of thousands to hundreds of thousands of kilobases long. The claims are directed to oligonucleotides with a sequence that “target” and “selectively hybridize” to these sections. However, the instantly claimed, generally recited oligonucleotides do not share any common structural element that is essential to the asserted utility of being associated with prostate cancer. Although the oligonucleotides all contain sequences that are found within the human genome, they are composed of different sequences in different chromosomes and distinct genetic contexts. None of these regions are structurally the same, nor do they encode transcripts that are the same. The only structural similarity present is that the claimed oligonucleotides contain nucleotides. However, the fact that the regions and oligonucleotides comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with prostate cancer. Thus when considering the different oligonucleotides that fall within the regions in the tables, recited in the alternative, there does not appear to be any common structure related to the function of the oligonucleotides in the claims.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
Claim Rejections - 35 USC § 112
Claims 7 and 17-29 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Relevant to the lack of particular structural limitations in the rejected claims drawn to oligonucleotides, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). 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) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The claims are directed to “oligonucleotides comprising probes” that target at least 10 different chromosomal regions set forth in the claims. The claim also recites that each probe “selectively” hybridizes to a segment of the chromosomal region it targets. Therefore, the claims encompass an enormous genus of possible oligonucleotide probes that functionally “selectively” hybridize to hundreds of thousands of different nucleotides. At paragraph 0024, the specification defines the term “hybridization” to include duplex formation with less than 100% complementarity between a probe and a target nucleic acid strand. Therefore, the claims also encompass oligonucleotides that are not 100% complementary to the targets they are designed to hybridize to. At paragraph 0025, the specification teaches that “stringent, sequence specific hybridization” conditions under which an oligonucleotide will hybridize only to the target sequence are sequence dependent and will be different under different circumstances. However, the specification does not teach what oligonucleotide sequences will only hybridize to regions set forth in the claims and not to any other nucleic acid target. Accordingly, the skilled artisan would not be able to determine which probes fall within the scope of the claimed genus (those that “target” and “selectively” hybridize) vs those that do not. Additionally, the designation of the chromosomal regions is not fixed. The specification does not teach what position “1” is to be able to determine which nucleotide sequences are encompassed by the regions set forth in the claimed table. Different versions of each chromosome exist in the art, and as the chromosomal sequences are updated, the nucleotide positions can change.
While the skilled artisan may be capable of making probes that hybridize to the claimed positions and test different conditions to determine which do not cross hybridize to other targets, 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.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of 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. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention 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 (1997); In re Gosteli, 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 is claimed.”). Thus, an applicant complies with the written description requirement “by describing 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.
Thus considering the breadth of the oligonucleotide probes required by the claimed kits, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Claims 7 and 17-29 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 claims are directed to “oligonucleotides comprising probes” that target at least 10 different chromosomal regions set forth in the claims. The claim also recites that each probe “selectively” hybridizes to a segment of the chromosomal region it targets. However, the metes and bounds of the term “selectively hybridizes” is not clear. At paragraph 0024, the specification defines the term “hybridization” to include duplex formation with less than 100% complementarity between a probe and a target nucleic acid strand. At paragraph 0025, the specification teaches that “stringent, sequence specific hybridization” conditions under which an oligonucleotide will hybridize only to the target sequence are sequence dependent and will be different under different circumstances. However, the specification does not teach what oligonucleotide sequences will only hybridize to regions set forth in the claims and not to any other nucleic acid targets. Therefore, the metes and bounds of the claimed oligonucleotides are not clear. Do the oligonucleotides have to be completely complementary to the target they hybridize to or is some variability allowed? What is the structure of oligonucleotides that fall within the scope of the claims vs those that do not? Accordingly, one of ordinary skill in the art would not be apprised of the scope of the claimed kits.
Additionally, the claimed table appears to recite numerical positions within particular chromosomes, however not only are the columns not defined, but no context is given as to what positions these numbers correspond to. What is the difference between Lch8 and Gchr8? Do they both refer to the same chromosome 8? Furthermore, it is not clear what the reference sequence is or what position “1” is. Different versions of each chromosome exist in the art, and as the chromosomal sequences are updated, the nucleotide positions can change. Therefore, the metes and bounds of the claimed regions, and therefore the probes that hybridize to them, is unclear.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682