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 .
DETAILED ACTION
Election of Species and Status of the Claims
Claims 1-4, 7, 9-11, and 14-16 are pending. Claims 14 and 16 are withdrawn from further consideration as being directed towards nonelected species until a generic claim has been found allowable (note that claims 14 and 16 limit the immune-suppressant of claim 11 to particular agents other than the elected species of ‘tacrolimus’). Claims 1-4, 7, 9-11, and 15 are examined on their merits.
Information Disclosure Statement
The Information Disclosure Statements filed on August 6th 2026 and June 25th 2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
35 U.S.C. § 102 Rejections Maintained
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.
The rejection of claims 1-2, 4, and 7 under 35 U.S.C. 102(a)(1) as being anticipated by Lederman (WO2021001458A1 published on January 7th 2021) is maintained.
Applicant’s arguments in the response filed on June 25th 2026 are acknowledged. Applicant argues that the claims, as amended:
“A method for treating or preventing chronic active antibody-mediated rejection (CAMR) with increased phosphorylation of Src and BTK in a subject having an organ transplant…”
are novel over Lederman, because Lederman makes no recitation that the CAMR carries the symptom of “increased phosphorylation of Src and BTK.” Applicant further states that “the finding that the phosphorylation of BTK is remarkably increased in CAMR patients is original to the inventors.” Applicant’s arguments are found not persuasive.
In essence, applicant is arguing that the symptom of “increased phosphorylation of Src and BTK,” is a property of the CAMR patient population that was previously unknown. That is, said increase in phosphorylation would be considered an inherent property of the CAMR patient population. See MPEP § 2112(I):
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.”
This deficiency is not corrected by the acknowledgement that the property was previously unknown in the prior art in Lederman, nor any other reference. See MPEP § 2112(II):
“There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.")”
Applicant is not purporting that the treatment of the patient population of “CAMR patients with increased phosphorylation of Src and BTK,” with applicant’s method gives superior results, but that “CAMR patients have unexpectedly high phosphorylation of Src and BTK and would benefit from applicant’s treatment. See Specification, paragraph [0015]:
“In the present disclosure, the inventor discovered that the phosphorylation of Src and BTK are remarkably increased in patients with chronic rejection, and Compound 1 showed the effects, including, alleviating CAMR; suppressing the elevation of B cells and plasma cells after kidney transplantation; preventing the infiltration of inflammatory cells in allogeneic kidneys, the activation of B cells via preventing the phosphorylation of BTK; reducing the secretion of proinflammatory cytokines and increased the secretion of anti-inflammatory cytokines, and protecting the allograft function, e.g., renal function, and improved the long-term survival rate of allogenic recipients.”
Following applicant’s characterization of the property of ‘increased phosphorylation of Src and BTK,’ it stands to reason that the patient population of Lederman (CAMR patients) would share said property, regardless of its disclosure in Lederman. See MPEP § 2112(V):
"[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same." In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977)
The property of “increased phosphorylation of Src and BTK,” is thereby considered to be inherent in the patient population of CAMR patients, and the 102 rejections over claims 1-2, 4, and 7 are maintained.
35 U.S.C. § 102(a)(1) Rejections Reiterated
Claims 1-2, 4, and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lederman (WO2021001458A1 published on January 7th 2021).
Claim 1 directed towards a method for treating or preventing chronic antibody-mediated rejection (CAMR) in a subject having an organ transplant, comprising administration of applicant’s elected species of:
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a BTK inhibitor known in the art as Zanubrutinib.
Lederman teaches the treatment of transplant rejection in a subject (Lederman, pg. 171, claim 65), and that the transplant rejection is chronic humoral rejection (also known as chronic antibody-mediated rejection) (Lederman, pg. 171, claim 66) via administration of a composition that includes Zanubrutinib (Lederman, pg. 175, claim 95). Lederman thereby anticipates claim 1.
Claim 2 requires that, in the method of claim 1, the subject has undergone an organ transplant and exhibits symptoms of AMR. Lederman teaches the treatment of AMR (humoral rejection) in a patient who has received an organ transplant (Lederman, pg. 171, claim 66), and that such a treatment comprises administration to patients who have exhibited symptoms of antibody-mediated rejection (Lederman, pg. 43, paragraph [0105]).
Claim 4 requires that, in the method of claim 1, the organ transplanted is the kidney. Lederman teaches treatment of rejection of a kidney transplant (Lederman, pg. 172, claim 69), anticipating claim 4.
Claim 7 is directed towards the method of claim 1, wherein the organ is a kidney and the symptoms of chronic antibody-mediated rejection comprise particular histological characteristics (note that the claim, as written, does not require that the patient receiving treatment exhibits said symptoms). Lederman teaches treatment of rejection of a kidney transplant (Lederman, pg. 172, claim 69) via administration of a composition that includes Zanubrutinib (Lederman, pg. 175, claim 95). Lederman thereby anticipates claim 7.
35 U.S.C. § 103 Rejections Maintained
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 rejection of claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Lederman (WO2021001458A1 published on January 7th 2021) is maintained.
Applicant’s arguments in the response filed on June 25th 2026 are acknowledged. Applicant argues that Lederman does teaches away from using a BTK inhibitor without an anti-CD154 antibody and never teaches Zanubrutinib alone. Therefore one of ordinary skill in the art would not reasonably use the combination for treatment of CAMR. Applicant further argues a case for unexpected results. Applicant’s arguments are found not persuasive.
Regarding the case for unexpected results, applicant’s results, as presented in examples 1-7 are not commensurate in scope with the combination treatment of claims 9-11, which is the subject of the present 103 rejection. The results only address the treatment with Zanubrutinib (relevant to the above 102 rejection) and not the treatment with the combination of Zanubrutinib and tacrolimus (as is presently being addressed). Therefore, applicant’s claim of unexpected results is considered unsubstantiated.
Regarding applicant’s arguments relating to the treatment of CAMR either with a BTK inhibitor alone, or with a BTK inhibitor and tacrolimus and NOT an anti-CD154 antibody, examiner notes that the claims, as written:
“A method for treating or preventing… comprising administering to the subject…”
currently encompass not only treatments with Zanubrutinib alone, nor combinations of Zanubrutinib and an immunosuppressant, but also the three-component regimen as suggested by Lederman.
The lack of suggestion for removing the anti-CD154 antibody from the regimen is not necessary, because the claim as written encompasses such a treatment.
Regarding applicant’s statement that both Zanubrutinib and tacrolimus are merely selected from a list present in Lederman, the described list (found in claims 66 and 95 of Lederman) is a list of immunosuppressive drugs for a combination treatment. Said immunosuppressive drugs would be considered equivalents known for the same purpose, and thus their combination would be considered prima facie obvious.
35 U.S.C. § 103 Rejections Reiterated
Claims 9-11 require that, in the method of claim 1, the BTK inhibitor is administered alongside an immune-suppressant, such as tacrolimus.
As stated in the above 102 rejection for claim 1, Lederman teaches the BTK inhibitor, Zanubrutinib, for the treatment of antibody-mediated rejection (Lederman, pg. 171, claim 66; pg. 175, claim 95). Lederman similarly teaches tacrolimus for the treatment of antibody-mediated rejection (Lederman, pg. 171, claim 66; pg. 175, claim 95). Lederman does not explicitly teach the combination of Zanubrutinib and tacrolimus. However, one of ordinary skill in the art would recognize that the two drugs, known in the art for the treatment of antibody-mediated rejection, could be used together for the same purpose. See MPEP 2144.06(I):
I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
As one of ordinary skill in the art would have a reasonable expectation of success in treating antibody-mediated rejection with a combination of Zanubrutinib (applicant’s elected BTK inhibitor) and tacrolimus (applicant’s elected immunosuppressant), claims 9-11 are prima facie obvious.
35 U.S.C. § 103 Rejections Necessitated by Amendment
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Lederman (WO2021001458A1 published on January 7th 2021).
Claim 15 limits the immune suppressant of claim 11 to tacrolimus. For the teachings of Lederman as they relate to claim 11, see the above 103 rejection for claim 11. Claim 15 is prima facie obvious for the same reasons as claim 11.
Conclusion
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 Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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