DETAILED ACTION
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 .
Claim Status
Claims 1-20 are currently pending and under exam herein.
Priority
The instant Application is a Continuation of US Application 15/783,776, filed 13 October 2017, now US Patent 11,462,296, and claiming the benefit of priority to US Provisional Application 62/407,987, filed 13 October 2016. Priority is acknowledged to 13 October 2013 for each of claims 1-20.
Information Disclosure Statement
The Information Disclosure Statement filed 16 January 2023 is in compliance with the provisions of 37 CFR 1.97 and has therefore been considered. A signed copy of the IDS is included with this Office Action.
Drawings
The drawings are objected to because part of the title in Figure 22 is truncated. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Note: All references to the Specification herein pertain to the PG publication: US20230095082A1.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Please see, for example, paragraphs [0101]; [0107]; and [0139].
Claim Rejections - 35 USC § 112(b)-Indefiniteness
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 1-16 and 20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and those claims dependent therefrom (2-16) and claim 20, recite, “quantifying an abundance level of each species-specific RNA sequence in the sample by determining an approximate number of times that each RNA sequence substantially aligned with exactly one corresponding gene occurs in the sample” wherein the claim is unclear with respect to the second recitation of “each RNA sequence substantially aligned with exactly one corresponding gene” as there are numerous recitations in the claim for “RNA” which refer to either the combined set of RNA or non-unique RNA or species-specific RNA and it is not immediately clear that the quantification step for each species-specific RNA is determined by determining, for example, the approximate number of times that each species-specific RNA sequence aligned. It is requested that clearer claim langue be recited to clarify which RNA is intended to be recited herein. For examination purposes the claim is interpreted as “approximate number of times that each species-specific RNA sequence substantially aligned…”
Claims 1-16 and 20 recite, “determining, based on one or more of the differentiation of the origin species or the quantification of the abundance level, that the tissue derived from the donor organism contains a biomarker indicative of at least one of: a disease status, a response of the host organism to the tissue derived from the donor organism, a response of tissue derived from the donor organism to transplantation within the host organism, or a response of the host organism to therapy administered to the host organism, wherein the claim is unclear with respect to the determination that a tissue contains a biomarker that is based on a differentiation of the origin of species or from a quantification of abundance level. It is not established in the claim the association between a determination of species origin or of a quantification of an abundance level the parameters that would indicate the presence of a biomarker that would further indicate a disease, a response of a host, a response of tissue to transplantation or the response of a host to therapy. For example, there is no relationship between the “abundance” and an indication of a biomarker. Typically that would include that some threshold or control be established such that an indication would be assessed. This is not present in the instant claims. Clarification is requested.
Claim Rejections - 35 USC § 112(a)-Written Description
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.
Claims 1-20 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims 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, at the time the application was filed, had possession of the claimed invention. The instant claims are directed to steps of xenografting and obtaining samples from a host organism that comprise a plurality of mRNA molecules. The instant Specification, however is solely directed to mRNA from exosomes (a specific membrane derived extra-vesicular source) and not to any and all sources of mRNA, including but not limited to those that include tissue derived mRNA; mRNA derived from whole blood; saliva derived mRNA; and/or other extra-cellular vesicles, including shed microvesicles (sMVs). The Specification discloses, for example, that the method of the claims includes obtaining exosomes [0005]-[0007]. Figures 28A-28C; 29A-29C; include workflow wherein OS-derived exosomes are defined using NGS. The Specification at [0040] discloses specifically that, “methods for identifying and detecting biomarkers based on nucleic acids from cells derived from tissue samples are subject to their own limitations. For example, such methods limit the scope of inquiry to the tissue samples themselves. Although nucleic-acid biomarkers identified in tissue samples (e.g., tumor biopsies) may indicate the presence of a disease or condition, such biomarkers do not reflect aspects of the disease or condition that occur outside of the sampled tissue. For example, while much of a cell's nucleic acids are located within the cell, some nucleic acids, such as RNA, can be transported out of the cell inside vesicles called exosomes. In particular, cell-free RNA may be found in the bloodstream of animals inside exosomes” and at [0041] that, “the RNA contained within exosomes may be indicative of its parent cell's transcription profile, and may provide biomarkers indicative of a patient's biological state. For example, the RNA contained within exosomes found within a patient's bloodstream may be indicative of one or more of the patient's risk of developing a condition or disease, the presence of the condition or disease, the progress of the condition or disease, or the potential future progress of the condition or disease. Indeed, some species of RNA contained within exosomes may be indicative of a metastatic cancer phenotype (i.e., that a cancerous condition is likely to metastasize), and may indicate that a process of metastasis of a primary tumor has begun” and finally at [0043] that, “thus, diagnostic and treatment-selection methods based on the detection of cell-free nucleic acid biomarkers derived from exosomes present in a patient's bloodstream may provide numerous clinical benefits over interventions based on the detection of a single nucleic acid biomarker derived from cells”.
The prior art indicates that there are multiple sources of mRNA including those from microvesicles of which exosomes are a part (see Lee et al. (2011) Vol. 33:455-467; IDS reference) teaching that cancer cells emit a mixture of vesicular, organelle-like structures (microvesicles, MVs) and that that may occur at the endosome or exosome pathways (abstract). Other sources of mRNA are well-known in the art, as described int eh Specification disclosing “tissues” for example above. However, the instant Specification is directed only to teaching and disclosing the isolation of exosomal mRNA as it is crucial to the invention. However, the instant Specification fails to find written description of any and all sources of mRNAs that would be operational herein.
As such, the claims are rejected herein for lack of written description.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,462,296 in view of Fujita et al. (Cancer Science (2016; April; Vol. 107:385-390; IDS reference).
Instant claim 1 is directed to:
A method comprising: xenografting tissue from a donor organism of a second species on to a host organism of a first species;
obtaining a sample derived from the host organism, wherein the sample comprises a plurality of molecules of messenger ribonucleic acid (mRNA);
determining, for substantially each molecule of the plurality of molecules of mRNA, a corresponding RNA sequence;
generating a combined dataset of RNA sequence reads by aligning each RNA sequence to a combined reference genome, wherein aligning each RNA sequence to the combined reference genome includes comparing a genomic location of each corresponding RNA sequence with a genomic location of a gene sequence of the combined reference genome, wherein the combined reference genome includes one or more gene sequences from at least a portion of a first genome derived from the first species and at least a portion of a second genome derived from the second species, and wherein the combined dataset of RNA sequence reads includes RNA sequence reads from both the first species and the second species;
filtering non-unique RNA sequence reads from the combined dataset by identifying species-specific RNA sequences exclusive to either the first species or the second species, wherein identifying species-specific RNA sequences includes determining, for each corresponding RNA sequence, whether the RNA sequence is substantially aligned with exactly one corresponding gene sequence of the combined reference genome;
at least one of:
differentiating an origin species of each species-specific RNA sequence in the filtered combined dataset by determining whether the corresponding RNA sequence is aligned to a gene sequence of the combined reference genome associated with the first genome of the first species or the second genome of the second species, or quantifying an abundance level of each species-specific RNA sequence in the sample by determining an approximate number of times that each RNA sequence substantially aligned with exactly one corresponding gene occurs in the sample; and
determining, based on one or more of the differentiation of the origin species or the quantification of the abundance level, that the tissue derived from the donor organism contains a biomarker indicative of at least one of: a disease status, a response of the host organism to the tissue derived from the donor organism, a response of tissue derived from the donor organism to transplantation within the host organism, or a response of the host organism to therapy administered to the host organism.
Claim 1 of the ‘296 patent is directed to:
A method comprising:
xenografting tissue from a donor organism of a second species on to a host organism of a first species;
obtaining a plurality of exosomes from a sample of bodily fluid derived from the host organism, wherein the plurality of exosomes comprises a plurality of molecules of messenger ribonucleic acid (mRNA);
identifying, for substantially each molecule of the plurality of molecules of mRNA, a corresponding RNA sequence;
generating a combined dataset of RNA sequence reads by aligning each RNA sequence to a combined reference genome, wherein aligning each RNA sequence to the combined reference genome includes comparing a genomic location of each corresponding RNA sequence with a genomic location of a gene sequence of the combined reference genome, wherein the combined reference genome includes gene sequences from at least a portion of a first genome derived from the first species and at least a portion of a second genome derived from the second species, wherein the combined reference genome indicates an origin species of each corresponding gene sequence, and wherein the combined dataset of RNA sequence reads includes RNA sequence reads from both the first species and the second species;
filtering non-unique RNA sequence reads from the combined dataset by identifying species-specific RNA sequences exclusive to either the first species or the second species, wherein identifying species-specific RNA sequences includes determining, for each corresponding RNA sequence, whether the RNA sequence is substantially aligned with exactly one corresponding gene sequence of the combined reference genome;
differentiating an origin species of each species-specific RNA sequence in the filtered combined dataset by determining whether the corresponding RNA sequence is aligned to a gene sequence of the combined reference genome associated with the first genome of the first species or the second genome of the second species;
quantifying an abundance level of each species-specific RNA sequence in the sample by determining an approximate number of times that each species-specific RNA sequence occurs in the filtered combined dataset; and
determining, based on the abundance level of species-specific RNA sequences associated with at least one of the first species or the second species in the sample of bodily fluid either increasing over a period of time or exceeding a predetermined threshold, that the tissue derived from the donor organism contains a biomarker indicative of at least one of:
a disease status,
a response of the host organism to the tissue derived from the donor organism, or
a response of the tissue derived from the donor organism to transplantation within the host organism.
The prior art to Fujita et al. disclose that extracellular vesicles (EVs), of which include exosomes, are considered important mediators in extracellular signaling pathways and include components such as DNA, mRNA and miRNA, and others, making them a focus for the research in the pathogenesis of disease (abstract at page 385 and page 386, col. 1). As such, the differences in the instant claim 1 and the patent claim 1 includes the recitation of exosomal mRNA wherein it would have been an obvious variant of source mRNA in the ‘296 patent to have included exosomal isolation.
Further, the instant application is a genus claim and also anticipates the recited species of “exosome” as exosomal mRNA is part of the genus of any and all mRNA.
Claims 2-20 herein and claims 2-26 of the ‘296 patent include variations of the above independent claims and are also obvious herein.
Conclusion
No claims are allowed.
E-mail Communications Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting following form via EFS-Web or Central Fax (571-273-8300): PTO/SB/439. Applicant is encouraged to do so as early in prosecution as possible, so as to facilitate communication during examination.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Inquiries
Papers related to this application may be submitted to Technical Center 1600 by facsimile transmission. Papers should be faxed to Technical Center 1600 via the PTO Fax Center. The faxing of such papers must conform to the notices published in the Official Gazette, 1096 OG 30 (November 15, 1988), 1156 OG 61 (November 16, 1993), and 1157 OG 94 (December 28, 1993) (See 37 CFR § 1.6(d)). The Central Fax Center Number is (571) 273-8300.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lori A. Clow, whose telephone number is (571) 272-0715. The examiner can normally be reached on Monday-Thursday from 12:00PM to 10:00PM ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz Skowronek can be reached on (571) 272-9047.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
/Lori A. Clow/Primary Examiner, Art Unit 1687
Prosecution Insights