DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 10/15/25 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/15/25 has been entered.
Claim 1 has been amended.
Claims 1 and 3 are pending and are under examination.
The 112b rejection and the 102/103 rejection over Lu are withdrawn in view of Applicant’s claim amendments
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:
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1 and 3 is/are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by or, in the alternative, under pre-AIA 35 U.S.C. 103(a) as obvious CN101606030A, as evidenced by Moon, 2023 (of record) and the machine English translation of said CN101606030A.
The ‘030 publication teaches a method of treating diseases associated with inflammation such as autoimmune diseases or organ transplantation comprising administering to a subject suffering therefrom an effective amount of activated FoxP3+ regulatory T cells (see abstract, pages 4-5 of the translation, and Fig. 11, in particular). The ‘030 publication teaches that the regulatory T cells are induced by activation with anti-CD3 antibodies, anti-CD28 antibodies, TGF-beta, IL-2, and rapamycin (see page 1, step 3, in particular, and also 4-5 of the translation and the drawings).
As evidenced by the instant specification FoxP3+ Tregs induced by activation with anti-CD3/CD28, IL-2, TGF-beta, and rapamycin overexpress LRIG1 (see, for, example, Figs. 2, 4 and 9-10 of the instant specification). Additionally, as evidenced by Moon, Tregs produced by the method of the ‘030 publication inherently overexpress Lrig1 (see materials and methods, Fig. 1, supplemental Fig. 2 and page 2, in particular). Thus, the activated FoxP3+ regulatory T cells administered in the method of the ‘030 publication, which are treated by a process identical to that recited in the present claims (i.e. activated with anti-CD3, anti-CD28, TGF-beta, IL-2, and rapamycin) would inherently overexpress Lrig-1. See MPEP 2112. Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103.
Applicant’s arguments filed 10/15/25 have been fully considered, but they are not persuasive.
Applicant argues that the ‘030 publication teaches additional steps/elements as compared to the claim method, particularly citing amplification with anti-CD4 and anti-CD27. Applicant argues that because additional elements are present in Lu, one could not predict if the Tregs activated therein would express Lrig-1.
As an initial matter, it is noted that the claimed method is a method “comprising” the recited steps, which is an open term that does not exclude unrecited steps or elements. Furthermore, the Tregs of the ‘030 publication are not amplified with anti-CD4 and anti-CD27, as argued by Applicant. Rather, the anti-CD27 and anti-CD4 are used in a selection step to select for Tregs which are stimulated for amplification using the same method as the instant claims, i.e. anti-CD3/CD28, IL-2, TGF-beta, rapamycin. Furthermore, the ’030 publication teaches that the CD4+CD27+ Tregs are also Foxp3+ (See page 4 of the translation and Fig. 1). In other words, the method of Treg amplification of the ‘030 publication falls within the scope of the instant claims, and comprises activating FoxP3+ Tregs with anti-CD3/CD28, TGF-beta, IL-2 and rapamycin. The property of overexpressing LRig11 would be inherent in the method of the ‘030 publication since the Tregs have been activated using identical conditions to those recited in the instant claims, and also because expressed of Lrig-1 is an inherently property of activated FoxP3+ Tregs as evidenced by Moon. Therefore, based on the facts and technical reasoning above, the overexpression of Lrig1 necessarily flows form the teachings of the prior art. See MPEP 2112, once a reference teaching a product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. Applicant cites no evidence to the contrary. “[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) (footnote and citation omitted). The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (citing Best, 562 F.2d at 1255).
The following are new grounds of rejection.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 3 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 present claims recite a method of treating a subject with immune-related “diseases”, wherein the diseases are selected from the group consisting of autoimmune diseases, GVHD, organ transplant rejection, etc. It is unclear if the treated subject needs to have more than one of the recited diseases, i.e. a subject with autoimmune disease and organ transplant rejection. Or would the claim encompass treating a subject, with a disease selected from those listed in the claim. On the one hand, the claim recites that the subject is one with “diseases”, which implies more than one disease from the listed group. On the other hand, autoimmune diseases or transplant rejection is characterize by multiple disease processes, and the claim could encompass treating a patient suffering from an autoimmune disease, or a transplant patient, for example. It is suggested to amend claim to recite treating a subject with “an” immune related disease, wherein the immune related disease is selected from the group consisting of.., to clarify the claim scope.
Claim(s) 1 and 3 is/are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over WO2010022341, in view of Lu, 2009, and as evidenced by Moon 2023 (all of record).
WO2010022341 teaches a method of treating autoimmune disorders or transplant related rejection and GVHD comprising administering to mammalian subject suffering therefrom a population of isolated and activated FoxP3+ regulatory T cells (see claim 67 and pages 1, 3-5, and 9-11, in particular). In particular, WO2010022341 teaches that the FoxP3+ Tregs are activated using anti-CD3 and anti-CD28, IL-2, and rapamycin, and that the isolation procedure selectively enriches for activated CD4+CD25+FoxP3+ Tregs that are highly suppressive (see page 3, 6, 10, and 22, in particular). WO2010022341 teaches that the regulatory T cells inhibit proliferation of activated T cells (see Fig. 6, in particular). As evidenced by the instant specification anti-CD3/CD28 activated and/or FOxP3+ regulatory T cells inherently overexpress LRIG1 (see, for, example, Figs. 2, 4 and 9 of the instant specification). This is also further evidenced by Moon, which teach that Lrig-1 is enriched in activated, CD4+CD25+FoxP3+ Tregs (see page 2, in particular). Thus, the activated FoxP3+ regulatory T cells administered in the method of the WO2010022341 would inherently overexpress Lrig-1.
WO2010022341differs from the claimed invention in that it does not explicitly teach activating with TGF-beta.
Lu teaches a method of making activated FoxP3+ regulatory T cells, wherein the regulatory T cells are activated with anti-CD3 antibodies, anti-CD28 antibodies, TGF-beta, IL-2, and rapamycin (see page 549, in particular). Lu teaches that the combination of TGF-beta with rapamycin induces higher percentage of FOxP3+ expression compared to rapamycin alone and that it can increase the suppressive function of CD4+CD25+FOxP+ Tregs.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include TGF-beta, as taught by Lu, in the Treg cultures of WO2010022341. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because Lu teaches that the combination of TGF-beta with rapamycin induces more FOxP3+ expression and that in can increase the suppressive function of CD4+CD25+FoxP3+ Tregs compared to rapamycin alone.
Alternatively, the present claims would also be obvious over Lu, in view of WO2010022341
Lu teaches a method of treating hepatic ischemic reperfusion injury comprising administering to mammalian subject suffering therefrom an effective amount of activated FoxP3+ regulatory T cells (see page 551, in particular). Lu teaches that the regulatory T cells are activated with anti-CD3 antibodies, anti-CD28 antibodies, TGF-beta, IL-2, and rapamycin (see page 549, in particular). Lu teaches that the regulatory T cell administration provides for treatment by downregulatory function of Th1 and TH17 cells and it would also inherently inhibit proliferation of activated T cells.
As evidenced by the instant specification FoxP3+ Tregs induced by activation with anti-CD3/CD28, IL-2, TGF-beta, and rapamycin overexpress LRIG1 (see, for, example, Figs. 2, 4 and 9-10 of the instant specification). Thus, the activated FoxP3+ regulatory T cells administered in the method of the Lu, which are treated by a process identical to that recited in the present claims (i.e. activated with anti-CD3, anti-CD28, TGF-beta, IL-2, and rapamycin) would inherently overexpress Lrig-1. Lu also teaches that hepatic reperfusion injury is associated with liver transplantation, and that Tregs are known to have a well-established role in maintenance of self-tolerance and control of autoimmunity and transplantation (see page 549 and 551, in particular).
Lu differs from the claimed invention in that it does not explicitly administer the Tregs to treat liver transplant rejection.
WO2010022341 teaches that FoxP3+Tregs can be administered for treating a variety of immune disorders, including autoimmune disease, or transplant rejection and GVHD (See page 4, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to administer the Treg of Lu, for treating autoimmune diseases, or transplant rejection and GVHD, as suggested by Lu and WO2010022341. For example, Lu teaches that hepatic reperfusion injury is associated with liver transplantation, and both Lu and WO2010022341 recognize the benefits of Treg administration for suppressing transplant rejection. For example, one could readily envision administering the Tregs of Lu for treating a subject with undergoing a liver transplant in need of treatment for reperfusion injury and in need of treatment to suppress liver transplant rejection and GVHD, thus meeting the limitations of the present claims.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644