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
Applicant’s amendment filed 05/15/2026 is acknowledged. Claim 5 is canceled. Claims 1-4, 6-8, and 10 are amended. Claim 15 is new.
Claims 1-4 and 6-15 are under examination.
Regarding newly amended and added claims, they are rejected under 35 USC § 112b, 102 and 103 as addressed below.
Withdrawn Rejections
All claim rejections under 35 USC § 112a and § 112b are withdrawn in light of the claim amendments.
Applicant’s arguments with respect to claim(s) 7-9 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Rejections Maintained/New Rejections Necessitated by Claim Amendments
Claim Rejections - 35 USC § 112(b)
Claim 8 contains the trademark/trade names Cinryze, and Rocunest. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a complement inhibitor and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 101
In Prometheus, the Court found that "[i]f a law of nature is not patentable, 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." Additionally, "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., ("[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."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claim as a whole, claims 10-12 and 14 are determined to be directed to a judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 74618) dated December 16, 2014 and 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
Step 1: Yes
The instant claims 10-12 and 14 are directed to a method of determining the likelihood of primary graft dysfunction, which is a process.
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility.
First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea) (Step 2A/1).
If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297) (Step2A/2). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew).
Step 2A/1: Yes
The instant claims 10-12 and 14 encompass detecting IL1β in a subject to determine the likelihood of primary graft dysfunction in a subject. Since higher levels of IL1β is known in the art to be associated with higher instances of primary graft dysfunction in lung transplant patients, which is a process that is governed by a law of nature, these claims are directed toward a judicial exception. The chemokine IL1β is a naturally occurring factor that is expressed differently during pathology of primary graft dysfunction apart from any human action. The relation between the levels of expression of the IL1β and pathology of primary graft dysfunction exists in principle and is a consequence of the ways these factors are metabolized by the body, entirely natural process, a natural phenomenon, and thus a judicial exception.
Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception.
Step 2A/2: No
In the instant case, the claims do not recite any additional elements to integrate the judicial exception into a practical application because all the steps (i.e. detecting a chemokine and identifying the subject at risk) of the claimed methods are limited to only those that detect a naturally occurring factor during a naturally occurring pathology. The instant situation is similar to the one in Mayo, wherein the claims recited method of administering drugs to a patient and measuring the levels of certain metabolites in the blood, wherein the level of metabolites indicates whether to adjust the dosage. The Supreme Court held that the claims recited a natural law and did not “include any “additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself.” Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S., 132 S. Ct. 77, 101 USPQ2d 1961 (2012).
Step 2B: No
Finally, claims 10-12 and 14 do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception because the active step of detecting a marker is a routine step recited at a high level of generality and encompasses well-understood and purely conventional routine techniques in the art. For example, Crespo et al., Frontiers, 2021 (see PTO-892 of record) teaches the use of a LABScreen multiplex assay to screen subjects prior to kidney transplant for problematic antibodies that may contribute to antibody-mediated rejection (pg. 2, first paragraph). The active step of identifying the subject as at increased risk solely recites the judicial exception (i.e. the relationship between IL1β and PGD) without additional elements. Altogether, the elements recited in the claim, whether viewed independently or as a whole do not amount to significantly more than the judicial exception itself.
Thus, for reasons fully explained above, claims 10-12 and 14 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
Response to Arguments
Applicant's arguments filed 05/15/2016 have been fully considered but they are not persuasive. Applicant argues that the amendments to claim 10 overcome the 101 rejection. However, the claim amendments do not overcome the analysis described in Step 2A/2 or Step 2B. There are no steps recited in addition to the judicial exception that integrate the judicial exception itself into a practical application. Detection of a chemokine and identifying the subject as at increased risk for a condition are not steps in addition to the judicial exception because they themselves are the judicial exception. Therefore, the claims fail Step 2A/2 analysis. Furthermore, the recited detection elements (i.e. ELISA, a multiplex immunoassay, etc.) are all well-understood, routine, and conventional in the art; therefore, the claims fail step 2B analysis. Therefore, the amended claims 10-12 and 14 remain rejected under 35 U.S.C. 101.
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 7-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Akbarpour et al., The Journal of Heart and Lung Transplantation, 2019 (hereafter Akbarpour.
Claims 7-9 are drawn to a method of preventing or treating the incidence of primary graft dysfunction in a subject, comprising screening for the presence of lung restricted autoantibodies, administering a complement inhibitor, wherein the complement inhibitor comprises Eculizumab, Cinryze, or Rocunest, and administering plasmapheresis and/or a complement blockade.
Akbarpour teaches that lung-restricted antibodies (LRA) are a risk factor for PGD (Abstract, line 7) and explicitly teaches screening for them in human patients (pg.598, right side, last paragraph). Akbarpour teaches that LRA can activate the complement system and that Eculizumab is an FDA approved complement inhibitor (pg. 598, first paragraph). Akbarpour further teaches that administration of a C1 esterase inhibitor of the complement system to patients mitigates PGD (pg. 598, left side, second paragraph). Lastly, Akbarpour teaches administering plasmapheresis in addition to complement inhibition (Fig. 2).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Akbarpour et al., The Journal of Heart and Lung Transplantation, 2019 (hereafter Akbarpour ) in view of Ghaidan et al., Nature Communications, 2022 (hereafter Ghaidan).
Claims 1 and 13 are drawn toward a method for preventing or reducing the incidence of primary graft dysfunction of a subject, wherein the subject is a human being, comprising screening the subject for lung restricted antibodies and administering an anti-IL1β antibody and/or a complement inhibitor.
Akbarpour teaches that lung-restricted antibodies are a risk factor for PGD (Abstract, line 7) and explicitly teaches screening for them in human patients (pg.598, right side, last paragraph). Akbarpour also teaches that PGD could be treated by inhibiting IL1β with an anti- IL1β antibody (Figure 2) and provides motivation for pursuing this option as a therapeutic target because of its “potential for rapid clinical translation” (pg. 597, right side, Lines 6-9). Furthermore, Akbarpour teaches that complement inhibition, if successful, would “immediately impact clinical practice” because of commercially available FDA approved complement inhibitor drugs (pg. 598, left side, first paragraph).
While Akbarpour suggests treating PGD using an anti- IL1β antibody, it does not teach actual implementation of IL1β inhibition therapy.
Ghaidan teaches that the incidence of primary graft dysfunction can be reduced by using IL1β adsorption, which captures the chemokine using a porous material, thereby mitigating its downstream effect (Figure 1 and Figure 5). Thus, Ghaidan demonstrates that blocking IL1β is an effective therapeutic route for PGD (pg. 1, Abstract).
It would have been obvious to one of skill in the art to combine Akbarpour and Ghaidan to arrive at an IL1β antibody to treat PGD. One of ordinary skill in the art would have been motivated to treat PGD with an anti-IL1β antibodies, based on the explicit suggestion from Akbarpour and because such antibodies, like Canakinumab, were commercially available. There would be a reasonable expectation of success using an IL1β antibody to treat PGD based on the Ghaiden’s results where cytokine adsorption dramatically reduced the incidence of PGD.
Response to Arguments
Applicant's arguments filed 05/15/2016 have been fully considered but they are not persuasive. Applicant addresses the individual teachings of Akbarpour and Ghaidan without
Applicant argues that Akbarpour does not teach the use of IL1β inhibition therapy as a treatment for PGD; however, Akbarpour explicitly suggests anti- IL1β therapy as a treatment for PGD (Figure 2).
Applicant argues that the IL1β antibody therapy taught by Akbarpour would not have a reasonable expectation of success because the relationship between IL1β and PGD was unknown at the time of filing; however, Akbarpour explicitly teaches that IL1β leads to extravasation (pg. 597 left side, second paragraph) and suggests the subsequent link to PGD by hypothesizing that extravasion enables LRA to bind to cognate antigens and induce lung injury (pg. 597, right side, top paragraph). An understanding of the exact mechanism by which IL1β leads to PGD is not necessary for one of ordinary skill in the art to have a reasonable expectation of success. Akbarpour’s teachings are sufficient to provide motivation for one of ordinary skill in the art to pursue IL1β inhibition as a treatment for PGD. Furthermore, the assessment for reasonable expectation of success of Akbarpour’s teachings must be made in view of the teachings from Ghaidan.
Applicant argues that Ghaidan does not cure the deficiencies of Akbarpour because it does not specifically teach IL1β inhibition as a treatment for PGD. While it is true that the cytokine adsorption taught by Ghaiden blocked other cytokines in addition to IL1β, an explicit link between IL1β and PGD in Ghaiden is not necessary, because Akbarpour already establishes that. Ghaidan provides support that the teachings in Akbarpour would have a reasonable expectation of success by demonstrating that blocking cytokines, including IL1β, reduced PGD.
The explicit teachings of Akbarpour to use an anti- IL1β antibody to treat PGD would have a reasonable expectation of success in view of the success taught by Ghaidan where blocking IL1β, among other cytokines, caused a dramatic reduction in the incidence of PGD.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Akbarpour and Ghaidan, as applied to claims 1, 4, and 13 above, and in further view of Crespo et al., Frontiers, 2021 (hereafter Crespo).
Claim 3 is drawn towards a screening step, wherein the screening comprises an autoantibody multiplex assay.
The teachings of Akbarpour and Ghaidan are described above.
Akbarpour and Ghaidan not teach that the antibody screen is achieved with an autoantibody multiplex assay.
Crespo teaches the use of a LABScreen multiplex assay to screen subjects prior to kidney transplant for problematic antibodies that may contribute to antibody-mediated rejection (pg. 2, first paragraph). This is the same brand of assay suggested in the instant application. Therefore, Crespo teaches that the desired kit in claim five was already commercially available.
It would have been obvious to modify the modified the screening step of anti-IL1β antibody treatment for PGD of Akbarpour and Ghaidan with autoantibody multiplex assay, as taught by Crespo. One of ordinary skill in the art would have been motivated to use a commercially available method for the screening step of modified Akbarpour and Ghaidan. For this reason, there would be a reasonable expectation of success.
Claims 2 and 6 is rejected under 35 U.S.C. 103 as being unpatentable over Akbarpour and Ghaidan, as applied to claims 1, 4, and 13 above, and in further view of Church et al. Current Opinion in Molecular Therapeutics, 2000 (hereafter Church).
Claims 2 and 6 are drawn towards an agent that blocks IL1β, comprising Canakinumab or Anakinra.
The teachings of Akbarpour and Ghaidan are described above.
The modified method of Akbarpour and Ghaidan do not teach an anti-IL1β antibody comprising Canakinumab or Anakinra.
Church teaches that Canakinumab was a known anti-IL1β antibody that could be using in humans for treatment of disorders.
It would have been obvious to modify the modified anti-IL1β antibody treatment for PGD of Akbarpour and Ghaidan with Canakinumab, as taught by Church, because it is a commercially available anti-IL1β antibody. One of ordinary skill in the art would be motivated to combine the teachings of Akbarpour, Ghaidan, and Church because Akbarpour provides explicit motivation by stating that commercially available antibodies provide “potential for rapid clinical translation” (pg. 597, right side, Lines 6-9). One of ordinary skill in the art would have a reasonable expectation of success because Canakinumab was FDA approved for use in humans.
Response to Arguments
Applicant's arguments filed 05/15/2016 have been fully considered but they are not persuasive. Applicant argues that Crespo and Church do not cure the deficiencies of Akbarpour and Ghaidan. Since the argument about the deficiencies of Akbarpour and Ghaidan, addressed above, is not persuasive, this argument is not persuasive.
Claims 10-12, 14, and 15 is/are is rejected under 35 U.S.C. 103 as being unpatentable over Ghaidan in view of Church, as evidenced by “Understanding ILD”, 2020, Pulmonary and Critical Care Medicine, pgs. 1-6 (hereafter Pulmonary and Critical Care) (see instant PTO-892).
Regarding claims 10-12, Ghaidan teaches detection of IL1β before, during, and after lung transplantation (Figure 3, and 4) using a bronchoalveolar lavage and a multiplex immunoassay (pg. 14, left side, second paragraph). As evidenced by Pulmonary and Critical Care, bronchoalveolar lavage is a method of lung tissue sampling (pg. 4, bottom paragraph) from the interstitial space (pg. 1, first paragraph). Ghaidan teaches that the presence of cytokines, including IL1β, indicates an inflammatory state (pg. 2, left side, second paragraph; Fig. 4) which increases the risk of PGD (pg. 12, right side, last paragraph; pg. 13, left side, first two lines). Regarding claim 15, Ghaidan teaches administration of an agent that blocks IL1β, namely a cytokine adsorber (Fig. 1; Fig. 4) after lung transplantation (pg. 13, “Animal preparation section”) .
Ghaidan does not teach that the subject is a human being.
Church teaches that IL1β can be detected in human beings (pg. 3, left side, last paragraph).
It would be obvious to substitute the subject in the method of treating PGD with cytokine adsorption in pigs, as taught by Ghaidan, to treat humans, as taught by Church, in order to arrive method of detection IL1β and treatment of PGD in humans. One of ordinary skill in the art would be motivated to modify Ghaidan’s method because cytokine reduction by adsorption has had successful results in heart and kidney transplants (pg. 2, left side, middle of second paragraph). There would be a reasonable expectation of success using Ghaidan’s method to detect humans at risk of PGD and mitigate its development after transplantation because of Ghaidan’s successful results in vivo (Figs. 4 and 5).
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MICHELLE C BUCCINI whose telephone number is (571)272-1352. The examiner can normally be reached M-F 7:30-5 EST.
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/MICHELLE CALLAHAN BUCCINI/Examiner, Art Unit 1675
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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