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 .
2. Applicant’s response filed on 10/10/2025 is acknowledged.
3. Claims 111, 115, 132-133, 136 and 159-180 are pending and under consideration.
4. Applicant’s IDS document filed on 10/10/2025 has been considered.
5. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
6. Claims 111, 115, 159-164, 168-173 and 177-180 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,345,751 (IDS filed on 12/22/2023) in view of Wilcox et al. (IDS filed on 12/22/2023; Reference 43) and Simister (PTO-892 mailed on 06/17/2025; Reference U).
Claims 1-40 of U.S. Patent No. 11,345,751 are directed to administering an antibody comprising reference SEQ ID NOs 19 and 24 (100% identical to instant SEQ ID NOs 19 and 24, respectively) to pregnant patients to treat alloimmune and/or autoimmune disorders including fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block.
The claimed invention differs from the prior art in the recitation of “wherein the composition is administered weekly to the pregnant woman beginning from any one of gestational weeks 12 to 16 of claims 111, 163 and 172; wherein the composition is administered from gestational week 13 to gestational week 35 of claims 159, 168 and 177; wherein the composition is administered from gestational week 14 to gestational week 35 of claims 160, 169 and 178; wherein the composition is administered from gestational week 15 to gestational week 35 of claims 161, 170 and 179; and wherein the composition is administered from gestational week 16 to gestational week 35 of claims 162, 171 and 180.
Wilcox et al. (IDS filed on 12/22/2023) teaches placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with minimal transfer in the first trimester. In the second trimester, the use of cordocentesis has demonstrated that fetal IgG rises from roughly 10% of the maternal concentration at 17–22 weeks of gestation, to 50% at 28–32 weeks (124). In the third trimester, the rate of IgG transfer rises significantly (particularly from 36 weeks), with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17–28 weeks. (In particular, page 7, whole document)
Simister et al. teaches during the first trimester of pregnancy, very little IgG is transported to the fetus. IgG is present within the syncytiotrophoblast late in the first trimester. FcRn is expressed in the syncytiotrophoblast by this time, and may protect IgG from intracellular degradation. At this stage of development, the syncytiotrophoblast covers a continuous cytotrophoblast layer. Cytotrophoblast cells neither express FcRn, nor contain IgG, and may prevent further penetration of the villi by IgG. As gestation progresses, the syncytiotrophoblast expands and the cytotrophoblast becomes increasingly discontinuous. These processes increase the surface area for IgG uptake from maternal blood and also allow access to the fetal vessel endothelium (In particular, page 3367).
It would have been obvious to one of ordinary skill in the art at the time of invention to have administered the antibodies to pregnant women in the second and third trimesters. This would be optimization of a method wherein one of ordinary skill in the art is administering an anti-FcRn antibody to inhibit disease of a fetus caused by maternal IgG antibodies whose transfer to the fetus is facilitated by FcRn.
It would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters based upon weight gain of the pregnant woman as recited in claim 173 because weight gain of the pregnant woman increases as the pregnancy progresses through the second and third trimesters.
It would have been obvious to have performed the method at the recited dosages and timing of administrations throughout pregnancy because the determination of all operable and optimal dosing and timing ranges is obvious because dosing and timing of administration are art-recognized result-effective variables which would have been routinely determined and optimized in the pharmaceutical art. The determination of the optimal dosage and timing is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. 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.
From the reference teachings, it is 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 reference, especially in the absence of evidence to the contrary.
Applicant’s arguments filed on 10/10/2025 have been fully considered, but are not found persuasive.
Applicant argues:
“The Office admits that the claims of the '751 patent do not teach or suggest the feature of "wherein the composition is administered weekly to the pregnant woman beginning from any one of gestational weeks 12 to 16. (Id at p. 4). In an attempt to cure this deficiency, the Office Cites Wilcox for its alleged teaching that placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17-28 weeks." (Id). The Office also cites Simister for its alleged teaching that biological processes increase the surface area of the syncytiotrophoblast for IgG uptake from maternal blood during gestation following "late in the first trimester." (Id). According to the Office, it would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters "based upon weight gain of the pregnant woman." (Id at p. 5). And the precise timing and dosing ranges are "result-effective variables which would have been routinely determined and optimized." (Id).
Applicant respectfully disagrees for at least the reason that none of the cited references, alone or together, teaches or suggests administration to the pregnant woman from any one of gestational weeks 12 to 16.
As previously demonstrated, the '751 patent claims do not once mention variable administration regimens. Thus, there is no reason to believe that a person of ordinary skill in the art would have adopted unguided treatment regimens to arrive at the claimed method without the benefit of hindsight.
Wilcox and Simister do not cure the deficiencies of the '751 patent. Wilcox and Simister are both high-level review articles that discuss the physiology of transplacental transfer of IgG from mother to fetus.
Neither Wilcox nor Simister teaches or suggests a method for treating or reducing the risk of developing hemolytic disease of the fetus and newborn (HDFN), let alone the specific administration regimen of the pending claims. Wilcox and Simister do not teach or suggest that an anti-FcRn antibody (such as the presently claimed N027) can be used therapeutically. Therefore, one of ordinary skill in the art would not rely on the disclosure of Wilcox and Simister for the preparation of a treatment regimen with any expectation of success.
Those of skill in the art would appreciate that identifying the time of treatment initiation for a fetal and neonatal alloimmune and/or autoimmune disorder is highly complex and cannot be predicted a priori. This is especially true here, where it was uncertain before Applicant's discoveries whether the anti-FcRn antibody would itself transfer from maternal to fetal circulation or if it would trigger a dose-dependent reduction of IgG in the fetus without direct fetal exposure.
In fact, the prevailing view of one of skill in the art in the field at the time of Applicant's effective filing date would have been to first administer an anti-FcRn at the beginning of pregnancy, much earlier than presently claimed. This position is supported by a 2011 publication in the Journal of Clinical Investigation by Li et al. (hereinafter "Li"). i
1 Li C., et al. The maternal immune response to fetal platelet GPIba causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies. J Clin Invest. 2011 Nov;121(11):4537-47. Provided in an Information Disclosure Statement filed 12/22/2023.
Li, et al. teaches the administration of an anti-FcRn antibody in a mouse model of fetal and neonatal immune thrombocytopenia (FNIT) from 1.5 days post coitum (d.p.c.) to delivery. (See Li at p. 4545, right column). As would be appreciated by one skilled in the art, pregnancy is detected by the presence of a "vaginal plug" in the female mouse analyzed every day after the male and female are housed together. In mouse models of pregnancy, 0.5 d.p.c. is considered day 0 (day the plug is found and 8-24 hrs following actual mating) and 1.5 d.p.c. is 24 hrs later. Thus, 1.5 d.p.c. is considered the beginning of pregnancy. At the time of Applicant's earliest effective filing date, one of skill in the art, guided by Li and general knowledge, would have been motivated to administer an anti-FcRn therapy at the beginning of pregnancy. This is in stark contrast to the method of the currently pending claims, where the composition is administered weekly to the pregnant woman beginning much later from any one of gestational weeks 12 to 16.
Taken together, the administration regimen of the currently pending claims is nonobvious over the '751 patent, Wilcox, and Simister.”
Applicant’s argument that one of ordinary skill in the art would have been motivated to “first administer an anti-FcRn at the beginning of pregnancy, much earlier than presently claimed.” due to the teachings of Li et al which is directed to studying miscarriage in mice. Contrary to Applicant’s assertion, one would not have been motivated to administer anti-FcRn therapy right after pregnancy to treat fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block. Li et al. is directed to preventing miscarriage in mice wherein they administered the antibody to the mice every 5 days from the beginning of pregnancy day 1.5 to delivery which is approximately 19-21 days in Balb/c mice. As such, they would have administered in total 4 times on days 1.5, 6.5, 11.5 and 16.5. Li et al. did not even determine the optimal dosing regimen on administering antibody to prevent miscarriage in mice most effectively. It is not taught that the first doses are critical to treat miscarriage. So, it is quite the stretch for Applicant to argue that the teachings of Li would have directed one of ordinary skill in the art to any type of timing of administration method in humans, much less directed them to the timing of administration of the antibodies to treat fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block at the beginning of pregnancy.
It is the Examiner’s position that it would have been obvious to have one of ordinary skill in the art would not be motivated to administered the antibodies to pregnant women in the second and third trimesters. This would be optimization of a method wherein one of ordinary skill in the art is administering an anti-FcRn antibody to inhibit disease of a fetus caused by maternal IgG antibodies whose transfer to the fetus is facilitated by FcRn in view of the teachings of Wilcox et al.(2017) and Simister at al. Wilcox teaches placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with minimal transfer in the first trimester. In the second trimester, fetal IgG rises from roughly 10% of the maternal concentration at 17–22 weeks of gestation to 50% at 28–32 weeks (124). In the third trimester, the rate of IgG transfer rises significantly (particularly from 36 weeks), with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17–28 weeks. (In particular, page 7, whole document). Simister et al. teaches during the first trimester of pregnancy, very little IgG is transported to the fetus. IgG is present within the syncytiotrophoblast late in the first trimester. FcRn is expressed in the syncytiotrophoblast by this time, and may protect IgG from intracellular degradation. At this stage of development, the syncytiotrophoblast covers a continuous cytotrophoblast layer. Cytotrophoblast cells neither express FcRn, nor contain IgG, and may prevent further penetration of the villi by IgG. As gestation progresses, the syncytiotrophoblast expands and the cytotrophoblast becomes increasingly discontinuous. These processes increase the surface area for IgG uptake from maternal blood and also allow access to the fetal vessel endothelium (In particular, page 3367).
These references provide the scientific basis for administering the antibodies to pregnant women in the second and third trimesters and that is sufficient basis for making the claimed invention obvious in view of the art.
Additionally, it would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters based upon weight gain of the pregnant woman as specifically recited in the claims because weight gain of the pregnant woman increases as the pregnancy progresses through the second and third trimesters.
Furthermore it remains true that the specification discloses on page 48, line 29 to page 49, line 5:
“In some cases, the compositions and pharmaceutical compositions described herein are administered to a pregnant woman throughout pregnancy. In some cases, the compositions and pharmaceutical compositions described herein are administered to a pregnant woman for around 5-25 weeks during pregnancy (e.g., around 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 weeks). In some instances, administration of the compositions and pharmaceutical compositions ceases after around gestational age 34 (week 34) (E.g., after week 34, 35, 36, or 37). In some instances, IVIG is administered to the pregnant woman after cessation of administration of the compositions and pharmaceutical compositions. In some instances, IVIG is administered between around 3-15 days (e.g., 3, 4,5,6,7,8,9, 10, 11, 12, 13, 14, or 15 days) after cessation of administration of the compositions and pharmaceutical compositions. In some cases, the time of IVIG administration after cessation of administration of the compositions and pharmaceutical compositions is adapted in accordance with factors such as weight gain of woman. In some instances, the compositions and pharmaceutical compositions
described herein are first administered after gestational age 12 (e.g. after 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30). In some cases they are administered during the pregnancy between gestational age 14 and 26 (e.g., 14 and 25; 15 and 25; or 15 and 26, etc.). In some cases they are administered during the pregnancy between gestational age 12 and 36(e.g., 12 and 36; 12 and 35; 12 and 34; 13 and 36; 13 and 35;13 and 34; 14 and 36; 14 and 35; 14 and 34; 15 and 36; 15 and 35;15 and 34; 16 and 36; 16 and 35; or 16 and 34; etc.).”
As such, there is no criticality of the method disclosed in the specification. The specification itself discloses that the antibody can be administered “throughout the pregnancy” and for around “5-25 weeks during the pregnancy”. Then, the specification discloses particular dosage durations which are extremely variable. There is nothing in the specification to support the criticality of a method which starts at gestational weeks 12 to 16 and goes from any amount of time or for the particular amounts of time specifically disclosed in the specification or claimed in the claims.
It is the Examiner’s position that it would have been obvious to have performed the method at the recited dosages and timing of administrations throughout pregnancy because the determination of all operable and optimal dosing and timing ranges is obvious because dosing and timing of administration are art-recognized result-effective variables which would have been routinely determined and optimized in the pharmaceutical art. Furthermore, the claims read on administration methods only preclude administration during the first trimester. It would be obvious to administer the composition for the second and third trimesters. It would be obvious to optimize the dosage and administration methods.
The rejection is maintained for reasons of record.
7. Claim 111, 115, 132-133, 136 and 159-180 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 12-19 and 23-26 of copending Application No. 17/260,318 in view of Buyon et al. (IDS filed on 12/22/2023; Reference 2), Roopenian et al. (IDS filed on 12/22/2023; Reference 27), Wilcox (IDS filed on 12/22/2023) and U.S. Patent No. 11,345,751 (IDS filed on 12/23/2023).
The claims in copending ‘318 are drawn to pharmaceutical compositions comprising antibodies. The antibodies have the sequences set forth as SEQ ID NO:1 and 2 (see ‘318 claims 11 and 22); these are identical to the instant sequences of SEQ ID NOs 19 and 24.
The claimed invention differs from the claims of the ‘318 application in the recitation of the administration method of instant claims.
U.S. Patent No. 11,345,751 teaches administering an antibody comprising reference SEQ ID NOs 19 and 24 (100% identical to instant SEQ ID NOs 19 and 24, respectively) to pregnant patients to treat alloimmune and/or autoimmune disorders including fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block.
Wilcox et al. (IDS filed on 12/22/2023) teaches placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with minimal transfer in the first trimester. In the second trimester, the use of cordocentesis has demonstrated that fetal IgG rises from roughly 10% of the maternal concentration at 17–22 weeks of gestation, to 50% at 28–32 weeks (124). In the third trimester, the rate of IgG transfer rises significantly (particularly from 36 weeks), with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17–28 weeks. (In particular, page 7, whole document)
Buyon et al. teaches that congenital heart block is an autoimmune disease that develops in fetuses and is caused by the transfer of antibodies from the pregnant mother to the developing fetus. This transfer occurs via the FcRn receptor (In particular, page 653, first paragraph, whole document). While maternal antibodies do not always cause disease in the developing fetus, their presence is a necessary precondition for the disease (In particular, page 654, first column, final paragraph; second column final sentence, whole document). Buyon teaches that IVIG is a likely candidate therapy for this condition, and that its efficacy seems to be mediated at least in part by blocking FcRn (In particular, page 659 final paragraph to page 660 first complete paragraph, whole document).
Roopenian et al. teaches that monoclonal antibodies against FcRn are therapeutics that can be used to block FcRn activity; (In particular, page 721 Box 1, page 722 Table 1, second column third paragraph, whole document)..
Therefore it would have been obvious to use the antibody products claimed in ‘318 by administering them to pregnant women at risk of transferring autoantibodies to their fetus, thereby arriving at the now-claimed method. Buyon teaches that such transfer can lead to autoimmune disease in the fetus, Roopenian teaches that one way to block this is by giving an antibody against FcRn. Roopenian also provides an expectation of success in doing so; see in particular Figure 1b and the accompanying legend, which indicates that in humans the FcRn is accessible via the maternal blood. U.S. Patent No. 11,345,751 teaches administering an antibody comprising reference SEQ ID NOs 19 and 24 (100% identical to instant SEQ ID NOs 19 and 24, respectively) to pregnant patients to treat alloimmune and/or autoimmune disorders including fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block.
It would have been obvious to one of ordinary skill in the art at the time of invention to have administered the antibodies to pregnant women in the second and third trimesters. This would be optimization of a method wherein one of ordinary skill in the art is administering an anti-FcRn antibody to inhibit disease of a fetus caused by maternal IgG antibodies whose transfer to the fetus is facilitated by FcRn.
It would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters based upon weight gain of the pregnant woman because weight gain of the pregnant woman increases as the pregnancy progresses through the second and third trimesters.
Claims 111, 115, 132-133, 136 and 159-180 are included in this rejection because it would have been obvious to have performed the method at the recited dosages and timing of administrations because the determination of all operable and optimal dosing and timing ranges is obvious because dosing and timing of administration are art-recognized result-effective variables which would have been routinely determined and optimized in the pharmaceutical art. The determination of the optimal dosage and timing is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. 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.
From the reference teachings, it is 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 reference, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Applicant’s arguments filed on 10/10/2025 have been fully considered, but are not found persuasive.
Applicant argues:
“Applicant does not agree with these rejections because the '318 application, the '334 application, and the '928 application have later patent term filing dates than the instant application and are therefore improper obviousness-type double patenting ("ODP") references. Specifically, the '318 application has a patent term filing date of July 19, 2019,2 the '334 application has a patent term filing date of July 19, 2019,3 and the '928 application has a patent term filing date of August 3, 2020,4 whereas the subject application has a patent term filing date of December 13, 2018.5 Even if the claims of the '318 application, the '334 application, and the '928 application were patentably indistinct from those of the subject application, the '318 application, the '334 application, and the '928 application are improper ODP reference applications because they are second-filed applications having later patent term filing dates than the subject application.
The Office responds that Applicant's arguments are not persuasive because the claims allegedly do not have support in U.S. Application No. 62/598,402 ("the '402 Application"). (Action at p. 14). Applicant disagrees. Support for the pending claims in the '402 Application may be found at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129. Thus, the pending claims are supported by the '402 Application.
Even if Applicant were not entitled to the earliest priority date (which Applicant does not concede), the MPEP provides guidance that the patent term filing date (not the priority date) is used for the double patenting analysis because that is the date on which the 20-year term is calculated. (See MPEP § 804(I)(B)(1)(a)). Here, the instant application has an earlier patent term filing date than U.S. Patent Applications 17/260,318, 17/260,334, and 17/597,928. Withdrawal of the provisional non-statutory double patenting rejection of the claims as allegedly unpatentable over the claims of the '318 application, the '334 application, and the '928 application when they are the only remaining rejections is requested.
2 The '318 application is the National State Entry of PCT/US19/42597 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,467, filed July 20, 2018.
3 The '334 application is the National State Entry of PCT/US2019/042615 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,367, filed July 20, 2018.
4 The '928 application is the National State Entry of PCT/US2020/044731 filed on August 3, 2020, and claims priority to United States Provisional Application Serial Number 62/881,897, filed August 1, 2019.s The subject application was filed on August 18, 2023, is a continuation of U.S. Pat. Application No. 16/771,147, filed June 9, 2020, which is the National State Entry of PCT/US2018/065568 filed on December 13, 2018, and claims the benefit of U.S. Provisional Application Serial Number 62/598,402, filed December 13, 2017.
Applicant's argument that the double patenting rejections are improper rejections is not persuasive.
It remains the Examiner’s position that instant claims do not have support in 62/598,402, so the instant application does not have an earlier patent term filing date. Applicant pointing to support for the pending claims in the '402 Application on “at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129” is not persuasive.
Furthermore, there is no instruction that Examiners are to look to the filing date of an issued patent when determining whether double patenting rejection should be maintained; and the provisional double patenting rejections are not the only remaining rejections.
As such these rejections will remain until the claims are amended or a terminal disclaimer is filed.
The rejection is maintained for reasons of record.
8. Claims 111, 115, 132-133, 136 and 159-180 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent 12,528,867 (PTO-892; Reference A) in view of Buyon et al. (IDS filed on 12/22/2023; Reference 2), Roopenian et al. (IDS filed on 12/22/2023; Reference 27), Wilcox et al. (IDS filed on 12/22/2023) and U.S. Patent No. 11,345,751 (IDS filed on 12/22/2023).
The claims in U.S. Patent 12,528,867 are drawn to pharmaceutical compositions comprising antibodies. The antibodies have the sequences set forth as SEQ ID NO:1 and 2 (see ‘334 claims 1); these are identical to the instant sequences of SEQ ID NOs 19 and 24.
The claimed invention differs from the claims of the U.S. Patent 12,528,867 in the recitation of the administration methods of instant claims.
U.S. Patent No. 11,345,751 teaches administering an antibody comprising reference SEQ ID NOs 19 and 24 (100% identical to instant SEQ ID NOs 19 and 24, respectively) to pregnant patients to treat alloimmune and/or autoimmune disorders including fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block.
Buyon et al. teaches that congenital heart block is an autoimmune disease that develops in fetuses and is caused by the transfer of antibodies from the pregnant mother to the developing fetus. This transfer occurs via the FcRn receptor (In particular, page 653, first paragraph, whole document). While maternal antibodies do not always cause disease in the developing fetus, their presence is a necessary precondition for the disease (In particular, page 654, first column, final paragraph; second column final sentence, whole document). Buyon teaches that IVIG is a likely candidate therapy for this condition, and that its efficacy seems to be mediated at least in part by blocking FcRn (In particular, page 659 final paragraph to page 660 first complete paragraph, whole document).
Wilcox et al. (IDS filed on 12/22/2023) teaches placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with minimal transfer in the first trimester. In the second trimester, the use of cordocentesis has demonstrated that fetal IgG rises from roughly 10% of the maternal concentration at 17–22 weeks of gestation, to 50% at 28–32 weeks (124). In the third trimester, the rate of IgG transfer rises significantly (particularly from 36 weeks), with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17–28 weeks. (In particular, page 7, whole document)
Roopenian et al. teaches that monoclonal antibodies against FcRn are therapeutics that can be used to block FcRn activity; (In particular, page 721 Box 1, page 722 Table 1, second column third paragraph, whole document)..
It would have been obvious to use the antibody products claimed in U.S. Patent 12,528,867 by administering them to pregnant women at risk of transferring autoantibodies to their fetus, thereby arriving at the now-claimed method. Buyon teaches that such transfer can lead to autoimmune disease in the fetus, Roopenian teaches that one way to block this is by giving an antibody against FcRn. Roopenian also provides an expectation of success in doing so; see in particular Figure 1b and the accompanying legend, which indicates that in humans the FcRn is accessible via the maternal blood. U.S. Patent No. 11,345,751 teaches administering an antibody comprising reference SEQ ID NOs 19 and 24 (100% identical to instant SEQ ID NOs 19 and 24, respectively) to pregnant patients to treat alloimmune and/or autoimmune disorders including fetal and neonatal alloimmune thrombocytopenia, hemolytic disease of the fetus and newborn and congenital heart block.
It would have been obvious to one of ordinary skill in the art at the time of invention to have administered the antibodies to pregnant women in the second and third trimesters. This would be optimization of a method wherein one of ordinary skill in the art is administering an anti-FcRn antibody to inhibit disease of a fetus caused by maternal IgG antibodies whose transfer to the fetus is facilitated by FcRn.
It would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters based upon weight gain of the pregnant woman because weight gain of the pregnant woman increases as the pregnancy progresses through the second and third trimesters.
Claims 111, 115, 132-133, 136 and 159-180 are included in this rejection because it would have been obvious to have performed the method at the recited dosages and timing of administrations because the determination of all operable and optimal dosing and timing ranges is obvious because dosing and timing of administration are art-recognized result-effective variables which would have been routinely determined and optimized in the pharmaceutical art. The determination of the optimal dosage and timing is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. 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.
From the reference teachings, it is 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 reference, especially in the absence of evidence to the contrary.
Applicant’s arguments filed on 05/19/2025 have been fully considered, but are not found persuasive.
Applicant argues:
“Applicant does not agree with these rejections because the '318 application, the '334 application, and the '928 application have later patent term filing dates than the instant application and are therefore improper obviousness-type double patenting ("ODP") references. Specifically, the '318 application has a patent term filing date of July 19, 2019,2 the '334 application has a patent term filing date of July 19, 2019,3 and the '928 application has a patent term filing date of August 3, 2020,4 whereas the subject application has a patent term filing date of December 13, 2018.5 Even if the claims of the '318 application, the '334 application, and the '928 application were patentably indistinct from those of the subject application, the '318 application, the '334 application, and the '928 application are improper ODP reference applications because they are second-filed applications having later patent term filing dates than the subject application.
The Office responds that Applicant's arguments are not persuasive because the claims allegedly do not have support in U.S. Application No. 62/598,402 ("the '402 Application"). (Action at p. 14). Applicant disagrees. Support for the pending claims in the '402 Application may be found at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129. Thus, the pending claims are supported by the '402 Application.
Even if Applicant were not entitled to the earliest priority date (which Applicant does not concede), the MPEP provides guidance that the patent term filing date (not the priority date) is used for the double patenting analysis because that is the date on which the 20-year term is calculated. (See MPEP § 804(I)(B)(1)(a)). Here, the instant application has an earlier patent term filing date than U.S. Patent Applications 17/260,318, 17/260,334, and 17/597,928. Withdrawal of the provisional non-statutory double patenting rejection of the claims as allegedly unpatentable over the claims of the '318 application, the '334 application, and the '928 application when they are the only remaining rejections is requested.
2 The '318 application is the National State Entry of PCT/US19/42597 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,467, filed July 20, 2018.
3 The '334 application is the National State Entry of PCT/US2019/042615 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,367, filed July 20, 2018.
4 The '928 application is the National State Entry of PCT/US2020/044731 filed on August 3, 2020, and claims priority to United States Provisional Application Serial Number 62/881,897, filed August 1, 2019.s The subject application was filed on August 18, 2023, is a continuation of U.S. Pat. Application No. 16/771,147, filed June 9, 2020, which is the National State Entry of PCT/US2018/065568 filed on December 13, 2018, and claims the benefit of U.S. Provisional Application Serial Number 62/598,402, filed December 13, 2017.”
Applicant's argument that the double patenting rejections are "improper" rejections is not persuasive.
It remains the Examiner’s position that instant claims do not have support in 62/598,402, so the instant application does not have an earlier patent term filing date. Applicant pointing to support for the pending claims in the '402 Application on “at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129.” is not persuasive.
Furthermore, there is no instruction that Examiners are to look to the filing date of an issued patent when determining whether double patenting rejection should be maintained.
As such these rejections will remain until the claims are amended or a terminal disclaimer is filed.
The rejection is maintained for reasons of record.
9. Claims 111, 115, 159-164, 168-173 and 177-180 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 89, 92-94, 97-98, 100-103, and 105-107 of copending Application No. 17/597,928 in view of Wilcox et al. (IDS filed on 12/22/2023).
The claims in copending ‘928 are drawn to methods of administration of the reference/instant sequences of SEQ ID NOs 19 and 24 to treat alloimmune and/or autoimmune disorders including hemolytic disease of the fetus and newborn
The claimed invention differs from the claims of the ‘928 application in the recitation of the administration methods of instant claims.
Wilcox et al. (IDS filed on 12/22/2023) teaches placental transfer of IgG occurs in an exponential fashion as pregnancy progresses, with minimal transfer in the first trimester. In the second trimester, the use of cordocentesis has demonstrated that fetal IgG rises from roughly 10% of the maternal concentration at 17–22 weeks of gestation, to 50% at 28–32 weeks (124). In the third trimester, the rate of IgG transfer rises significantly (particularly from 36 weeks), with the increase of fetal IgG concentrations between 29 and 41 weeks of gestation doubling that of 17–28 weeks. (In particular, page 7, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have administered the antibodies to pregnant women in the second and third trimesters. This would be optimization of a method wherein one of ordinary skill in the art is administering an anti-FcRn antibody to inhibit disease of a fetus caused by maternal IgG antibodies whose transfer to the fetus is facilitated by FcRn.
It would have been obvious to one of ordinary skill in the art to have administered the antibodies in the second and third trimesters based upon weight gain of the pregnant woman because weight gain of the pregnant woman increases as the pregnancy progresses through the second and third trimesters.
Claims 111, 115, 159-164, 168-173 and 177-180 are included in this rejection because it would have been obvious to have performed the method at the recited dosages and timing of administrations because the determination of all operable and optimal dosing and timing ranges is obvious because dosing and timing of administration are art-recognized result-effective variables which would have been routinely determined and optimized in the pharmaceutical art. The determination of the optimal dosage and timing is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. 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.
From the reference teachings, it is 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 reference, especially in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Applicant’s arguments filed on 05/19/2025 have been fully considered, but are not found persuasive.
Applicant argues:
“Applicant does not agree with these rejections because the '318 application, the '334 application, and the '928 application have later patent term filing dates than the instant application and are therefore improper obviousness-type double patenting ("ODP") references. Specifically, the '318 application has a patent term filing date of July 19, 2019,2 the '334 application has a patent term filing date of July 19, 2019,3 and the '928 application has a patent term filing date of August 3, 2020,4 whereas the subject application has a patent term filing date of December 13, 2018.5 Even if the claims of the '318 application, the '334 application, and the '928 application were patentably indistinct from those of the subject application, the '318 application, the '334 application, and the '928 application are improper ODP reference applications because they are second-filed applications having later patent term filing dates than the subject application.
The Office responds that Applicant's arguments are not persuasive because the claims allegedly do not have support in U.S. Application No. 62/598,402 ("the '402 Application"). (Action at p. 14). Applicant disagrees. Support for the pending claims in the '402 Application may be found at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129. Thus, the pending claims are supported by the '402 Application.
Even if Applicant were not entitled to the earliest priority date (which Applicant does not concede), the MPEP provides guidance that the patent term filing date (not the priority date) is used for the double patenting analysis because that is the date on which the 20-year term is calculated. (See MPEP § 804(I)(B)(1)(a)). Here, the instant application has an earlier patent term filing date than U.S. Patent Applications 17/260,318, 17/260,334, and 17/597,928. Withdrawal of the provisional non-statutory double patenting rejection of the claims as allegedly unpatentable over the claims of the '318 application, the '334 application, and the '928 application when they are the only remaining rejections is requested.
2 The '318 application is the National State Entry of PCT/US19/42597 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,467, filed July 20, 2018.
3 The '334 application is the National State Entry of PCT/US2019/042615 filed on July 19, 2019, and claims priority to United States Provisional Application Serial Number 62/701,367, filed July 20, 2018.
4 The '928 application is the National State Entry of PCT/US2020/044731 filed on August 3, 2020, and claims priority to United States Provisional Application Serial Number 62/881,897, filed August 1, 2019.s The subject application was filed on August 18, 2023, is a continuation of U.S. Pat. Application No. 16/771,147, filed June 9, 2020, which is the National State Entry of PCT/US2018/065568 filed on December 13, 2018, and claims the benefit of U.S. Provisional Application Serial Number 62/598,402, filed December 13, 2017.”
Applicant's argument that the double patenting rejections are improper rejections is not persuasive.
It remains the Examiner’s position that instant claims do not have support in 62/598,402, so the instant application does not have an earlier patent term filing date. Applicant pointing to support for the pending claims in the '402 Application on “at least at page 11, lines 10-12, page 46, lines 22-25, and original claims 111 and 129.” is not persuasive.
Furthermore, there is no instruction that Examiners are to look to the filing date of an issued patent when determining whether double patenting rejection should be maintained and the provisional double patenting rejections are not the only remaining rejections.
As such these rejections will remain until the claims are amended or a terminal disclaimer is filed.
The rejection is maintained for reasons of record.
10. No claim is allowed.
11. 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 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 date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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January 24, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1644