DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of species combination: CD28, ITK, ICOS, and LCK in the reply filed on 8/15/2025 is acknowledged. Claims 35-37 remain withdrawn from consideration as being directed to non-elected inventions, as a result of the restriction requirement dated 5/11/2023 and applicant’s response dated 8/25/2023.
Status of Claims
This office action on the merits is in response to the RCE filed 4/24/2025. Currently, claims 25, 27-37, 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 Claims 35-37 are withdrawn from consideration as being drawn to a non-elected invention.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, 27-34, 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 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Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.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 Rejection
Claims 25, 27-34, 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 claims 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 any common structural element that is essential to the asserted utility of being associated with subclinical acute rejection. 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.
Claim Rejections - 35 USC § 112
112, 2nd paragraph
Claim 30 is 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 recites “wherein has or is at risk of having said slow progressive IPF”. The claim appears to be missing the phrase “said subject”. Without this limitation, the claim is indefinite because the meaning of, and the metes and bounds of, the claim are unclear. Appropriate correction is required.
112, 4th paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 33 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 33 ultimately depends from claim 25, which limits the biological sample to PBMC, serum or plasma. However claim 33 recites that the biological sample are lung cells. Therefore, the claim does not further limit claim 25. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
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.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 25, 27-34, 39, 40, 43, and 44 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Konishi (Konishi et al; Am J Respir Crit Care Med, vol 180, 2009, pages 167-175) in view of Affymetrix GeneChip 1.0 ST array (2007).
Konishi teaches analysis of gene expression in lung tissue samples in patients with stable IPF as well as those with IPF-AEx (rapid deteriorations). Konishi teaches obtaining samples from patients who had pulmonary function tests (see page 168, table 1), and extracting RNA from lung tissue as well as plasma. Konishi teaches measuring RNA expression using the Agilent 4x4K whole human genome microarray. Konishi teaches patients with rapid deteriorations vs those with stable IPF. Although Konishi does not identify the patients as having “rapid” vs “slow progressive” IPF, the designation of “slow progressive” vs “rapid” IPF are considered obvious in view of the clinical manifestations described by Konishi because patients with stable IPF did not deteriorate as rapidly as those with IPF-AEx. Although Konishi does not teach treating the patients, including with a transplant, it would have been prima facie obvious to the ordinary artisan before the invention was made to treat patients by Konishi 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.
Konishi does not teach whether the expression levels of LCK, ICOS, CD28 or ITK could be measured with the Agilent array system taught. However, Affymetrix teaches the GeneChip 1.0 ST array system. Affymetrix teaches that the array system offers an advanced and cost effective gene expression profiling option for whole transcriptome coverage. It is noted that the Affymetrix 1.0 ST array system comprises probes for measuring the expression level of 28,869 well annotated genes, including LCK, ICOS, CD28, and ITK. 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 substituted the array system taught by Affymetrix for the array used in the method of Konishi as this represents the substitution of one element for another with a reasonable expectation of success. Konishi teaches the need to study global gene expression signatures of acute exacerbations of IPF. Therefore the ordinary artisan would have been motivated to analyze global gene expression signatures using any number of the arrays available in the prior art for such purposes in the method of Konishi, including the Affymetrix 1.0 array system. In doing so, the ordinary artisan would necessarily measure the gene expression of all the genes probed by the array system, including instantly claimed LCK, ICOS, CD28, and ITK.
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, 27-34, 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, 27-34, 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.
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.
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