Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
RESPONSE TO APPLICANT’S AMENDMENT
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/25/25 has been hereby entered.
2. Claims 1-3, 10-23 are pending.
Claims 10 -22 stand withdrawn from further consideration by the Examiner, 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions.
Claims 1-3 and 23 read on a method of treating a human a human organ transplant recipient comprising administering an effective amount of stem cell mobilizer agent and an immunosuppressive agent are under consideration in the instant application.
3. 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 of this title, 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 negatived by the manner in which the invention was made.
4. This application currently names joint inventors. In considering patentability of the claims under 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(f) or (g) prior art under 35 U.S.C. 103(a).
4. Claims 1-3, 23 stand rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over Trotter et al ( Liver Transplantation, 2002,v.8 pages 212-218), US Patent Application 20210395339 , US Patent 6,162426, US Patent 5718893 and US Patent Application 20130202553 ,US Patent Application 20120225028 and WO 2006116185 in view US Patent Application 20220193046 and US Patent Application 20070225217; Yamazaki et al ( Pharmaceutical research, 2009, v.26, pages 1832-1837 US Patent Application 20110182898 and US Patent 6,140472 and US Patent Application 20110281814, US Patent Application 20100178271, US Patent Application 20130072482 and US Patent Application 20060178351 for the same reason set forth in the previous Office action, mailed on 06/2525.
Applicant’s argument filed on 09/25/25 have been fully considered but have not been found convincing.
Applicant asserts that the amended claims now recited administering Tacrolimus in the amount of about 0,0001 mg.kg to about 0.005 mg.kg. None of the prior art references teach said amount.
Contrary to Applicants assertion it is the Examiner’s position that it would be conventional and within the skill of the art to identify an effective amount of administered Tacrolimus. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
Moreover it is noted that the instant Specification explicitly teaches that in case of injection it is usually convenient and well know to give an intravenous route in an amount of about 0.0001ug-30 mg per day to adults (at bout 60 kg). In addition, as is evidence from Yamazaki et al ( Pharmaceutical Research 2009, v.26 pages 1832-1837) administering a low dose of tacrolimus ( 0,001mg/kg) was well know and routinely used at the time the invention was made.
Thus, as dosing was well known to the ordinary artisan, it would have been obvious to optimize dosing regimens to meet the needs of the patient at the time the invention was made.
US Patent Application ‘814 teaches various protocols of subcutaneous administering of AMD3100 to the subject, including at least three times a week or once every three weeks ( see entire document ,paragraphs 0080, 0087, 0114, 0118 in particular).
US Patent Application ‘271 teaches various protocols of ADM3100 administering to the subject, including subcutaneous and at least once a day ( see entire document ,paragraphs 0023, 0072, 0075 in particular).
US Patent Application ‘482 teaches various protocols of tacrolimus administering to the subject, including subcutaneous and at least once a day ( see entire document ,paragraph 0737 in particular).
US Patent Application ‘351 teaches various protocols of tacrolimus administering to the subject, including subcutaneous and at least once every three days ( see entire document ,paragraphs 0183,0189, 0210 in particular).
It is the Examiner’s position that newly claimed timing of administering of AMD3100 and Tacrolimus to the recipient would be an obvious variation of the prior art recited protocols .
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
As has been stated previously, Yamazaki et al ( Pharmaceutical research, 2009, v.26, pages 1832-1837) teaches that administering tacrolimus in the dose range from 0.001 to 0.5 mg/kg was well know and routinely used to one skilled in the art. Thus, it is the Examiner position that it would be conventional and within the skill of the art to determine an effective doses of tacrolimus to be administered. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
With regards to Applicant’s statement that Yamazaki et al teaches away from using subcutaneous administration of tacrolimus.
A prior art reference may be considered to teach away when "a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant." In re Gurley , 27 F.3d 551, 553, 31 USPQ2d 1130, 1131 (Fed. Cir. 1994). General skepticism of those in the art -- not amounting to teaching away -- is also "relevant and persuasive evidence" of nonobviousness. Gillette Co. v. S.C. Johnson & Son, Inc. , 919 F.2d 720, 726, 16 USPQ2d 1923, 1929 (Fed. Cir. 1990). In effect, "teaching away" is a more pointed and probative form of skepticism expressed in the prior art. In any case, the presence of either of these indicia gives insight into the question of obviousness.
In the instant case Yamazaki et al., explicitly teaches that subcutaneous co-administering of tacrolimus results in decreasing of C1h values , decreased the titers of antibodies in a manner similar to i.v. administration ( see page 1835 left column).
It is the Examiner’s position that one skilled in the art upon reading Yamazaki et al., would not be discourage from administering tacrolimus by subcutaneous injection.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
As dosing was known to the ordinary artisan, it would have been obvious to optimize dosing regimens to meet the needs of the patient at the time the invention was made.
As has been stated previously, US Patent Application 20220193046 teaches administering Tacrolimus to the recipient of organ transplant. US Patent Application 20220193046 teaches administering 0,02 mg/kg of Tacrolimus, i.e. an obvious variation of a instantly claimed dose. ( see entire documents, paragraphs 0177 in particular).
US Patent Application 20070225217 teaches administering Tacrolimus for prevention and treatment of transplantation rejection in the recipient organ transplant ( see entire documents). US Patent Application 20070225217 teaches administering about ) 0.1-3 mg/per day. It is the Examiner’s position that, assuming the average weight of the person to be about 70-100 kg, the instantly claimed dose of about 0,01 mg/kg is an obvious variation of a instantly claimed dose.
All the claimed elements were known in the prior art and one skill in the art could have combine the elements as claimed by known methods with no change in their respective function and the combination would have yield predictable results to one of ordinary skill in the art at the time of the invention ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007).
Thus it would have been obvious to one of the ordinary skill in the art at the time the invention was made to use an effective amount Tacrolimus in a method of treating a human organ transplant recipient with a reasonable expectation of success because the prior art teaches administering Tacrolimus for prevention and treatment of transplantation rejection in the recipient organ transplant
Trotter et al., teach a method of treating a human organ transplant recipient, comprising administering to said recipient an effective amount of immunosuppressive agent Tacrolimus. Trotter et al., teach that Tacrolimus should be administering at low dose about 2mg/per day to the recipient. ( see entire document, Abstract and Method in particular). It is the Examiner’s position that, assuming the average weight of the person to be about 70-100, the instantly claimed dose of about 0,01 mg/kg is an obvious variation of a recited dose of 2 mg/per day.
US Patent Application ‘339 teach a method of treating a human organ transplant recipient, comprising administering to said recipient an effective amount of immunosuppressive agent Tacrolimus alone or in combination with other agents. US Patent Application ‘339 teach dose variation of administered Tacrolimus to minimize toxicity ( see entire document, paragraphs 0032, 0343. Though US Patent Application ‘339 does not explicitly teaches administering immunosuppressive agent at a dose of about 0,0001mk/kg to about 0.01 mg/ it would be conventional and within the skill of the art to identify the optimal dose for administering immunosuppressive agent. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
US Patent ‘426 teaches a method of treating a human organ transplant recipient, comprising administering to said recipient an effective amount of stem cell mobilizer agent G-SCF ( see entire document Paragraph 8 in particular).
US Patent ‘893 teaches a method of treating a human organ transplant recipient, comprising administering to said recipient an effective amount of stem cell mobilizer agent G-SCF ( see entire document Paragraphs 12, 14, and Examples in particular).
US Patent Application ‘553 teaches a method of treating a human organ transplant recipient, comprising administering to said recipient an effective amount of stem cell mobilizer agent such as G-SCF ( see entire document Paragraphs 0322 and 0329 in particular).
US Patent Application’934 teaches the use of AMD3100 as a stem cell mobilized when administered to the recipient( see entire document, paragraphs 0065 in particular).
WO’ 185 teaches the use of AMD3100 as a stem cell mobilized when administered to the recipient ( see entire document, Pages 2, in particular).
US Patent Application ‘898 teaches the advantages of subcutaneous administering immunosuppressive agent to the subject receiving organ transplantation ( see entire document, paragraphs 0154 ,0155 0166 in particular).
US Patent Application ‘472 teaches the advantages of subcutaneous injection of immunosuppressive agent to the subject receiving organ transplantation ( see entire document, paragraphs 7 and 53 in particular).
All the claimed elements were known in the prior art and one skill in the art could have combine the elements as claimed by known methods with no change in their respective function and the combination would have yield predictable results to one of ordinary skill in the art at the time of the invention ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007).
Thus it would have been obvious to one of the ordinary skill in the art at the time the invention was made to administer immunosuppressive agent by subcutaneous injection in a method of treating a human organ transplant recipient with a reasonable expectation of success because the prior art teaches the advantages of subcutaneous injection of immunosuppressive agent to the subject receiving organ transplantation.
All the claimed elements were known in the prior art and one skill in the art could have combine the elements as claimed by known methods with no change in their respective function and the combination would have yield predictable results to one of ordinary skill in the art at the time of the invention ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007).
Thus it would have been obvious to one of the ordinary skill in the art at the time the invention was made to use an effective amount of stem cell mobilizing agent and immunosuppressive agent in a method of treating a human organ transplant recipient with a reasonable expectation of success because the prior art teach that each of said agents can be successfully used for treating a human organ transplant recipient
“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, 205USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06).
From the teachings of the references, it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
7. Claims 1-3, 23 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of co-pending Application US 20180200232
Although the conflicting claims are not identical, they are not patentably distinct from each other because claims 1-21 of co-pending Application US 20180200232 recite a method of treating an organ transplant recipient comprising administering to the recipient a low dose of Tacrolimus in an amount sufficient to mobilize stem cells to the peripheral blood of the recipient.
This is a provisional nonstatutory double patenting rejection because the conflicting claims have not in fact been patented.
It is noted that Applicant requested to hold that provisional double patenting rejection in abeyance until allowable subject matter is identified.
5. Claims 1-3, 23 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of US Patent 11,291,657
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims 1-5 of US Patent 11,291,657 are drawn to a composition comprising stem cell mobilizer and immunosuppressive agent that are used in the presently claimed methods, and wherein the presently claims methods are disclosed in the specification of the US Patent 11,291,657.
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
It is noted that Applicant requested to hold that provisional double patenting rejection in abeyance until allowable subject matter is identified.
6. Claims 1-3, 23 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable claims 1-14 of co-pending Application US 20220142992; claims 1-17 of US 20180200232 , claims 1-10 of co-pending US Patent Application 20220184043; claims 1-10 of co-pending US Patent US 20200038381, claims 1-10 of co-pending Application US 20220184043.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims 1-14 of co-pending Application US 20220142992; claims 1-17 of US 20180200232 , claims 1-10 of co-pending US Patent Application 20220184043; claims 1-10 of co-pending US Patent US 20200038381, claims 1-10 of co-pending Application US 20220184043 are drawn to a composition comprising stem cell mobilizer and immunosuppressive agent that are used in the presently claimed methods, and wherein the presently claims methods are disclosed in the specifications of Application US 20220142992; US 20180200232 , US Patent Application 20220184043; US Patent US 20200038381, Application US 20220184043.
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
It is noted that Applicant requested to hold that provisional double patenting rejection in abeyance until allowable subject matter is identified.
7. No claim is allowed.
8. All claims are either identical to or patentably indistinct from claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114.
Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 extension fee 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.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michail Belyavskyi whose telephone number is 571/272-0840. The examiner can normally be reached Monday through Friday from 9:00 AM to 5:30 PM. A message may be left on the examiner's voice mail service. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Daniel Kolker can be reached on 571/ 272-3181
The fax number for the organization where this application or proceeding is assigned is 571/273-8300
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/MICHAIL A BELYAVSKYI/Primary Examiner, Art Unit 1644