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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/9/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of species blood pressure medication and ace inhibitor in the reply filed on 5/6/2026 is acknowledged.
Status of Claims
Currently claims 89, 91-98, 100-101, 103, 106-113, 115, and 117-125 are pending. The election of species between the 3 different rs/SEQ ID NOS 1-3 and an inversion are withdrawn. Claims 121, 122, 124, and 125 are withdrawn from consideration as being directed to non elected therapeutic species. Accordingly, an office on the merits of claims 89, 91-98, 100-101, 103, 106-113, 115, 117-120, and 123 is set forth herein. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments follow. 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Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 101
Claims 89, 91-98, 100-101, 103, 106-113, 115, 117-120, and 123 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites methods for selecting and treating a human subject for treatment to reduce the risk of developing renal failure as well as selecting a subject in need of screening for renal disease by detecting risk alleles in APOL1, which is a natural correlation. Although the specification at table 1 teaches: SEQ ID NO: 1 risk allele is a G, SEQ ID NO: 2 risk allele is a G, and SEQ ID NO: 3 risk allele is del6, the claims are not limited to detecting those alleles as evidenced by the dependent claims which allow for detecting the presence or absence of those alleles. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “selecting a human subject”, which is a recitation of an abstract idea because it encompass conclusions and decisions which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite multiple steps. The first step involves the use of generic nucleic acids (eg: probe) to detect the APOL1 risk alleles, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method. The same analysis holds for elements such as “biannual or annual screening” (claim 100, 115). The second step is directed to “selecting a human subject” which is an abstract idea and recites the natural correlation. Therefore, this step does not integrate the JE into a practical application because it is merely a recitation of the JE itself. Although the claims recite “treating”, this step is conditional because the claims appear to encompass detecting the absence of the risk alleles. This is evidenced, for example, by claim 100, which recites “detecting the presence or absence of a G allele…”.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the limitations directed to samples are considered insignificant post solution activity. The steps of “contacting a biological sample from the human subject with a nucleic acid probe” or a “primer” as well as “detecting [determining] formation of a hybridization complex” are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response dated 9/9/2025 traverses the rejection and asserts that the claims have been amended to include a specific treatment. This argument has been thoroughly reviewed but was not found persuasive because while claims 89 and 103 appear to require detecting a specific allele, the claims which depend from them, such as claims 100 and 115, respectively, allow for detection of the absence of the risk allele. It is for this reason, that is the potential conditionality of the treatment or the fact that the treatment is administered regardless of risk allele, in which case the treatment would not be considered a practical application because it does not integrate the JE (that is the natural correlation between the particular allele and renal failure) itself, that the rejection is maintained.
Claim Rejections - 35 USC § 112
Written Description
Claims 89, 91-98, 100-101, 103, 106-113, 115, 117-120, and 123 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to methods which comprise identifying any structurally undefined APOL1 inversion “risk allele” which possess the functionality of being associated with renal failure or renal disease.
Relevant to the lack of particular structural limitations in the rejected claims drawn to nucleic acids, 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.
In the case of the instant claims, the functionality of identifying APOL1 inversions which are risk alleles diagnostic of predisposition or risk for developing renal disease or renal failure is a critical feature of the claimed methods.
The specification teaches identifying several polymorphisms in the APOL1 gene associated with predisposition to renal disease. These are a G at rs73885319 which results in S342G substitution, a G at rs60910145 which results in a I384M substitution, and a 6 base pair deletion at rs71785313 which results in the deletion of N388 andY389 (table 1, page 33). The specification also teaches one gene inversion, termed the “G3” risk allele which inverts a segment of DNA including the 5’ end of APOL4, all of APOL2, and the 5’ end of APOL1 producing an APOL4/APOL1 hybrid gene (page 33). It should be noted that the specification does not teach an inversion within the coding or non-coding region of APOL1 in the absence of the G3 allele.
The specification does not teach the functional effect of these polymorphisms or inversions related to predisposition to kidney disease or renal failure. Therefore, the skilled artisan would be unable to predictably correlate any other structural change in any other region of the APOL1 gene with the claimed function.
The lack of predictability as to a functional association between the claimed mutations and renal disease is acknowledged in the art. Tzur (Tzur et al; Human Genet, vol 128, 2010, pages 345-350) teaches:
Functional assays of the effect of the APOL1 missense variants described herein in appropriate experimental model systems will be needed to link the strong and biologically plausible association to a functional pathogenic pathway in kidney disease and to the possible selective factors which contributed to the observed African allele frequency distribution.domain of the APOL1 gene product”.
Although the general methodology for detecting polymorphisms and variations, such as inversions, is known, 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. This finding is also emphasized in Ex Parte Kubin (No. 2007-0819, Bd. Pat. App. & Int. May 31, 2007), wherein it is stated that: “Although there is often significant overlap” between the enablement and written description requirements, “they are nonetheless independent of each other.” University of Rochester, 358 F.3d at 921, 69 USPQ2d at 1891. An “invention may be enabled even though it has not been described.” Id. Such is the situation here. While we conclude one skilled in the art would have been able to make and use the full scope of claim 73 through routine experimentation, we find Appellants did not describe the invention of claim 73 sufficiently to show they had possession of the claimed genus of nucleic acids. See, e.g., Noelle v. Lederman, 355 F.3d 1343, 1348, 69 USPQ2d 1508, 1513 (Fed. Cir. 2004) (“invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed”).
The claims encompass a genus of structurally undefined inversions which require a specific functionality. The genus includes a large number of mutations/variants for which no written description is provided in the specification. This large genus is represented in the specification by a single inversion, however this disclosure does not provide for a predictable association with any inversion in the APOL1 gene as is broadly claimed. Here, no common element or attributes of the sequences are disclosed which would permit selection of sequences as polymorphisms. No structural limitations or requirements which provide guidance on the identification of sequences which meet the functional limitations of associating predisposition to renal disease is provided. The specification provides no correlation between the structure of the recited polymorphisms and the claimed function of such polymorphisms. Therefore, the polymorphisms and single inversion taught are not representative of the genus of any inversion in APOL1 associated with renal disease because it is not clear which inversions within the coding or non-coding region of the APOL1 gene would have the same affect. Therefore the specification fails to teach how to distinguish members of the claimed genus of polymorphisms which possess the claimed functionality from non-members.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that “Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed.” (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.) In the instant case, the specification fails to teach the necessary common attributes or features of the genus of encompassed nucleic acids and polymorphisms in view of the species disclosed. As such, one of skill in the art would not recognize that applicant was in possession of the genus of polymorphisms encompassed by the broadly claimed invention.
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.
An adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the '525 patent, "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel, 984 F.2d 1164, 1171, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself." Id. at 1170, 25 USPQ2d at 1606.
Thus considering the breadth of the polynucleotide inversions required by the claimed methods, 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.
Indefinite
Claims 89, 91-98, 100-101, 103, 106-113, 115, 117-120, and 123 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 specification at table 1 teaches: SEQ ID NO: 1 risk allele is a G, SEQ ID NO: 2 risk allele is a G, and SEQ ID NO: 3 risk allele is del6. Since the independent claims are directed to detecting these SEQ ID NOS, they appear to require detecting a G in SEQ ID NO: 1, a G in SEQ ID NO: 2, or the deletion of SEQ ID NO: 3. However, the claims which depend from them, such as claims 100 and 115, respectively, allow for detection of the absence of the risk allele. The metes and bounds of the required allele detection in the claims is therefore unclear. Appropriate correction is required.
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 89, 91-98, 100-101, 103, 106-113, 115, 117-120, and 123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-21 of U.S. Patent No. 10,130,632, or claims 1-13 of US Patent 10, 940,151, (herein referred to as “patented claims) each in view of Pays (WO2011/020865) and Munar (Munar et al; American Family Physician, 2007, vol 75, 1487; downloaded from the internet, pages 1-22). .
The patented claims are directed to treating renal disease in a subject with risk alleles of APOL1, including S342G and I384M (SEQ ID NOS 1 and 2). The patented claims also teach administering a therapeutic, such as an ACE inhibitor (blood pressure medication), to subjects for treating renal disease. It would have been prima facie obvious to the ordinary artisan to first detect the risk alleles and to screen subjects for renal disease or renal failure prior to treatment as set forth in the patent claims. Although the patent claims do not teach obtaining a sample and using nucleic acid probe hybridization or primer amplification techniques to detect the APOL1 alleles, Pays teaches methods of obtaining a sample and detecting the same APOL1 alleles using probe hybridization and primer amplification techniques (para 0013). Therefore, it would have been prima facie obvious to the ordinary artisan to use the probe hybridization methods of detecting APOL1 alleles taught by Pays with a reasonable expectation of success, to detect the APOL1 alleles of the patented claims. Although the patent claims do not teach to administer the ACE inhibitor (blood pressure medication) at a reduced dose to subjects with the alleles, Munar teaches that adjusting doses of certain medications in patients with kidney disease (see whole document). Munar teaches administering decreased doses of certain ACE inhibitors by as much as 50% of the regular dose. Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have administered ACE inhibitors at a reduced dose to subject with the risk alleles as taught by the patent claims because Munar teaches that certain medication dosages should be adjusted to avoid severe adverse effects.
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
Prosecution Insights