DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Claims
Currently, claims 25, 27-32, 34-37, 39-40, and 43-44 are pending in the instant application. Claims 35-37 are withdrawn from consideration as being drawn to a non-elected invention. Claims 25, 27-32, 34, 39-40, and 43-44 are currently under examination. 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 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Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.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 Rejection
Claims 25, 27-32, 34, 39-40, and 43-44 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements when the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. See MPEP § 2117 which provides guidance on the analysis of a proper Markush group.
Regarding claims 25, 27-34, 39-40, and 43-44, the Markush group in question is any alternatively recited combination comprising four or more of the structurally and functionally different genes in claim 25.
Regarding “single structural similarity”, the MPEP at 2117 IIA states that a recognized physical, chemical, or an art recognized class is a class where there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. It is specifically stated that “Thus a Markush grouping is ordinarily proper if all the members for the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (emphasis added)”.
Therefore, in analysis of whether a claim contains an improper Markush grouping, the MPEP states: A Markush claim contains an “improper Markush grouping” if either (emphasis added): (1) the members of the Markush group do not share a ‘single structural similarity’ or (2) the members do not share a common use.”
In the instant case, the genes do not share a common structural element that is essential to the asserted utility of being associated with IPF. First, the different genes are from different parts of the human genome and are composed of different nucleic acid sequences encoding functionally different proteins. Furthermore, the prior art does not teach, nor is it clear from their nature, that all of the functionally different genes possess the property of being differentially expressed biomarkers of subclinical acute rejection.
For example:
The gene encoding PLBD1 is located on chromosome 12. PLBD1’s related pathways are Glycerophospholipid biosynthesis and Acyl chain remodeling.
The gene encoding FLT3 is on chromosome 13, and encodes a class III receptor tyrosine kinase. Mutations in the gene are common in AML.
The gene encoding DOCK10 is located on chromosome 2, and encodes a member of the dedicator of cytokines protein family. Diseases associated with DOCK10 include Adams-Oliver Syndrome.
The gene encoding GBP4 is located on chromosome 1. GBP4 is a guanylate binding protein. Diseases associated with GBP4 include Patent Foramen Ovale.
Therefore it is clear that when considering the different genes, even in different combinations of 4 genes, recited in the alternative in the rejected claims, there does not appear to be any common structure related to the function of the genes individually, or any particular combination of 4 or more genes, let alone an association with IPF.
Furthermore, the recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different gene combinations. The only structural similarity present is that all the genes are made up of nucleotides. However, comprising 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 IPF.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
Response to Arguments
The response traverses the rejection. The response asserts that the claims do not present the type of ambiguity that the improper Markush doctrine is intended to address. This argument has been thoroughly reviewed but was not found persuasive for the reasons already made of record above. The response further asserts that the rejection is not well founded because the relevant inquiry is whether, in the context of the claimed invention, the recited RNAs share the claimed functional role and that the recited RNAs are members of an IPF biomarker signature which the specification teaches are assessed for expression changes to evaluate IPF progression and prognosis. The response concludes that the disclosures provide a common class and a common use in the precise context of the claimed invention. This argument has been thoroughly reviewed but was not found persuasive. The MPEP at 2117 IIA states that a recognized physical, chemical, or an art recognized class is a class where there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. It is specifically stated that “Thus a Markush grouping is ordinarily proper if all the members for the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (emphasis added)”. This applies when "there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention." However the specification has not shown evidence establishing an expectation in the art that the members of the claimed class, encompassing a wide range RNA molecules encoding disparate proteins having a disparate chemical and physical properties, will behave the same way in the context of the claimed invention. See MPEP § 2117(IV)(D) ("the members of the Markush grouping do not share a substantial structural feature" where "defining component (b) represent a plurality of chemical classes with varying structures"). Additionally, neither the specification nor the art has established that the members share a structural feature that is essential their common use as biomarkers for IPF. Therefore, it is not clear from their very nature or from the prior art that all members possess the property of functioning as IPF prognostic biomarkers in an expression detection assay. The response then asserts that the Board has repeatedly rejected the same type of over-narrow Markush analysis citing Ex pare Ward (Appeal 2021-003776; PTAB June 10, 2022) and Ex party Ren (Appeal 2015-004371; PTAB Dec. 28, 2016), and asserts that the decisions are applicable in the instant situation because the recited RNAs function as members of a disclosed IPF prognostic biomarker. This argument has been thoroughly reviewed but was not found persuasive. It is pointed out that these decisions are not precedential and that the examiner has followed the guidance in the MPEP in presenting the rejection. For these reasons and the reasons made in the rejection above, the rejection is maintained.
Claim Rejections - 35 USC § 102
Claims 25, 27, 30, 32, 34, 39, 40, and 43 are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Herazo (Herazo et al; Am J Respir Crit Care Med, vol 183, May 2001, abstract, cited in the IDS filed 5/2/2022).
Herazo teaches measuring expression levels of ICOS, CD28, ITK, and LCK in PBMC samples from patients with IPF with differences in mortality. These patients are therefore inherently at risk of having slow or rapid IPF. Accordingly, Herazo anticipates the claimed invention.
Response to Arguments
Applicant refers to an affidavit or declaration filed in the prior application 16/031,384. Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of the prior application do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
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 25, 27-32, 34, 39, 40, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,036,069. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope because the ‘069 application teaches detecting expression of CD28, ICOS, ITK, and LCK, as is encompassed by the instant claims, in the same patients. Although the ‘069 claims do not teach treating the patients with a lung transplant, it would have been prima facie obvious to the ordinary artisan before the invention was made to treat patients taught by the ‘069 claims for the obvious benefit of relieving IPF symptoms. As lung transplant is a known method of treatment in the art for IPF, it would have further been prima facie obvious to the ordinary artisan to provide lung transplant to those patients in need. It would have additionally been prima facie obvious to use different biological samples, including PBMCs and lung cells for the obvious benefit of obtaining a more comprehensive gene expression signature.
Claims 25, 27-32, 34, 39, 40, 43, and 44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,961,582 in view of Konishi and Affymetrix GeneChip ST 1.0 array. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope. The ‘582 claims teach detecting expression of CD28, ICOS, ITK, and LCK, as is encompassed by the instant claims, in the same patients. Although the ‘582 claims do not teach assaying the gene expression using microarray analysis, Konishi and Affymetrix teach arrays for gene expression analysis. Additionally, Konishi teaches the need for detecting nucleic acid expression in patient with IPF. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have also assayed mRNA expression analysis in the methods of the ‘582 claims as taught by Konishi. Although the ‘582 claims do not teach treating the patients with a lung transplant, it would have been prima facie obvious to the ordinary artisan before the invention was made to treat patients taught by the ‘582 claims for the obvious benefit of relieving IPF symptoms. As lung transplant is a known method of treatment in the art for IPF, it would have further been prima facie obvious to the ordinary artisan to provide lung transplant to those patients in need.
Response to Arguments
The response traverses the rejection and asserts that the pending claims “require detecting expression levels of four or more recited RNA biomarkers using a microarray or PCR in the presently claimed sample and assay context, and include limitations directed to rapid or slow progressive IPF and treatment-related dependent claims that are not rendered obvious by the cited patent claims.”. This argument has been thoroughly reviewed but was not found persuasive because the patent claims are also directed to detecting expression levels of CD28, ITK, ICOS, and LCK (‘582 claims) or CD28, ITK, ICOS, LCK, PLBD2, TPST1, C19orf59, IL7R, KLF12, and NAP1L2 (‘069 claims) in the context of IPF using PCR (‘069 claims) in the same biological samples. Although the ‘582 claims are directed to western blotting or ELISA, it would have been obvious to detect expression using PCR or microarrays in view of the cited prior art. For these reasons and the reasons already made of record above, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
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 this Group is (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1634
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