DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The Amendment filed 09/03/2025 in which claims 48 and 56 were amended, and claim 63 was added, has been entered. Claims 1-47, 52 were previously canceled.
Claims 48-51, 53-63 are under examination on the merits.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
(previous rejection, maintained and modified as necessitated by amendment as to claims 48-51, 53, 54, 57, 58, 61, and 62) Claims 48-51, 53, 54, 57, 58, 61, and 62 are rejected under 35 U.S.C. 103 as being unpatentable over D5290C00003, in view of Zhu et al. (prior art of record).
See claims 48-51, 53, 54, 57, 58, 61, and 62 as submitted on 09/03/2025.
Regarding amended claim 48, it is noted that the new recitation of “wherein the method comprises determining if the subject is entering or experiencing their first or second RSV season, and, if the subject is in their first RSV season, determining if the subject weighs < 5 kg or > 5 kg, wherein the method further comprises intramuscularly administering the single fixed dose of nirsevimab based on the determination,” did not introduce any new limitations because the claims already recited the same exact limitations prior to the amendment. Specifically, the claims as previously submitted on 04/23/2025 already included the limitations of determining if the subject is entering or experiencing their first or second RSV season and determining if the subject weighs < 5 kg or > 5 kg because the “wherein” clause in claim 48 as submitted on 04/23/2025 required such determination/stratification of the subjects. Thus, the steps of “determining if the subject is entering or experiencing their first or second RSV season” and “determining if the subject weighs < 5 kg or > 5 kg” were already present in the method of claim 48 as previously submitted on 04/23/2025. Similarly, the new recitations of “intramuscularly” and “nirsevimab” were already present in claim 48 as previously submitted on 04/23/2025. Therefore, it is herein submitted that new recitation indicated above of ““wherein the method comprises determining if the subject is entering or experiencing their first or second RSV season, and, if the subject is in their first RSV season, determining if the subject weighs < 5 kg or > 5 kg, wherein the method further comprises intramuscularly administering the single fixed dose of nirsevimab based on the determination,” does not introduce any new limitations to the claim. Accordingly, the rejection under 35 U.S.C. 103 set forth in the previous Non-Final Office Action mailed on 06/04/2025 still applies to amended claim 48.
As previously explained, D5290C00003 teaches:
A method of preventing (immunoprophylaxis) respiratory syncytial virus (RSV) lower respiratory tract infection LRTI by administering a single fixed dose of nirsevimab (MEDI8897) in a formulation intramuscularly (IM) to pediatric patients (page 14, lines 2-5; page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3; page 18, 2.1.2 under “Secondary Objectives,” statement 2).
Nirsevimab being present in the formulation at a concentration of 100 mg/mL (page 37, table 4.5.1-1, first row).
Pediatric patient groups receiving a single dose IM of either 10 mg, 25 mg, or 50 mg (page 16, ¶ 2, lines 10-11).
the pediatric population having a mean weight (+/- SD) of 6.82 (+/- 1.90) kg (< 5 kg and ≥ 5 kg) and receiving nirsevimab (page 16, ¶ 2, lines 15-17) during their first RSV season.
Nirsevimab for preventing (immunoprophylaxis) RSV for all infants entering their first RSV season (page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3).
Nirsevimab for passive immunization of a pediatric population at high risk of RSV infection with chronic lung disease (CLD) or congenital heart disease (CHD) entering their first and second RSV season (page 14, ¶ 1, lines 2-5), wherein CLD and CHD are clinical symptoms of patients at high risk of severe RSV infection (page 12, ¶ 2, lines 2-4).
Pediatric patient groups receiving a single nirsevimab dose intramuscularly of either 10 mg, 25 mg, or 50 mg (page 16, ¶ 2, lines 10-11).
Stratification of patients based on whether the patient entering their first RSV season at the time of screening or not (page 3, under “Target Subject Population”).
D5290C00003 does not explicitly teach a single dose of 100 mg for patients in their first year of life and/or entering or experiencing their first RSV season; nor does it teach a dose of 200 mg for patients in the second year of life and/or entering or experiencing their RSV season, and at high risk of severe RSV infection.
Zhu et al. teach the administration of a single fixed dose of 50 mg of nirsevimab (MEDI8897) (page 7, column 1, ¶ 1, lines 5-8). Zhu et al. further teach incorporating the effect of body weight and age of the patient on clearance of the drug into the pharmacokinetic (PK) model to adjust for growth and maturation of infants and predict the concentration of nirsevimab (MEDI8897) in blood serum after a single IM dose for the benefit of enabling once-per season dosing (page 7, column 1, ¶ 1; page 7, column 2, ¶ 1; page 8, fig. 5C).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have modified the method, as previously disclosed by D5290C00003, in order to have provided the weight range of pediatric patients entering their first season for the corresponding doses of 50 mg, 100 mg, and 200 mg in view of the predictive pharmacokinetic (PK) model taught by Zhu et al. for the benefit of enabling once-per season dosing.
One of ordinary skill in the art would have had a reasonable expectation of success for incorporating the effect of body weight and age of the patient to adjust for growth and maturation of infants as taught by Zhu et al. There would have been a reasonable expectation of success given that the PK model disclosed by Zhu et al. was developed for palivizumab, another RSV monoclonal IgG1 antibody which targets the highly conserved F glycoprotein of RSV and has been demonstrated to be effective for RSV prevention (Zhu et al. [page1, column 2, ¶ 3, lines 1-4]), and the methods of anti-RSV antibody dosing are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
With respect to patients at high risk of severe disease, it is noted that this limitation applies to patients in their second year of life and/or entering or experiencing their second RSV who are at least 7 month of age. It is well known in the art that RSV seasons have a typical duration of 5 months (See Zhu et al.) In the United States, the RSV season onset ranges from mid-September to mid-November and season offset ranging from mid-April to mid-May (See Zhu et al.) A child entering their second RSV season will be at least 7 months old given that children born at the end of their first RSV season, for example in the month of April, will reach their second RSV season in October of the year of their birth. According to the WHO growth charts of weight-for-age for girls and boys (prior art of record), the majority of 7-month-old children are expected to have a body weight > 5 kg.
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have modified the method, as previously taught by D5290C00003, in order to have provided a larger dose (200 mg) of nirsevimab (MEDI8897) for infants in their second year of life who are of greater body weight, including patients at high risk of severe RSV infection, in view of the predictive pharmacokinetic model taught by Zhu et al. for the benefit of enabling once-per season dosing.
Similarly, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have modified the method, as previously taught by D5290C00003, in order to have provided a larger dose (200 mg) of nirsevimab (MEDI8897) for infants at high risk of severe RSV infection who are at least 7 months of age and are entering or experiencing their second RSV season, in view of the predictive pharmacokinetic model taught by Zhu et al. for the benefit of enabling once-per season dosing.
One of ordinary skill in the art would have had a reasonable expectation of success for incorporating the effect of body weight and age of the patient to adjust for growth and maturation of infants as taught by Zhu et al. given that the PK model taught by Zhu et al. was developed for palivizumab, another RSV monoclonal IgG1 antibody which targets the highly conserved F glycoprotein of RSV and has been demonstrated to be effective for RSV prevention (Zhu et al. [page1, column 2, ¶ 3, lines 1-4]), and the methods of anti-RSV antibody dosing are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Therefore, the claimed ranges merely represent routine optimization of the values of the cited prior art.
Regarding claim 49, it is noted that no amendments were introduced to claim 49. D5290C00003 teaches nirsevimab for passive immunization of a pediatric population at high risk of RSV infection with chronic lung disease (CLD) or congenital heart disease (CHD) entering their first and second RSV season (page 14, ¶ 1, lines 2-5), wherein CLD and CHD are clinical symptoms of patients at high risk of severe RSV infection (page 12, ¶ 2, lines 2-4).
Regarding claim 50, it is noted that no amendments were introduced to claim 50. As previously explained, the claim recites a subject “entering or experiencing their first RSV season… has chronic lung disease, congenital heart disease...”, this subject is within the pediatric population taught by D5290C00003 “children with CLD or CHD “entering their first and second RSV season” (page 14, ¶ 1, lines 2-5).
Regarding claim 51, it is noted that no amendments were introduced to claim 51. As previously explained, the claim recites “the subject entering or experiencing their second RSV season weighs ≥ 5 kg,” as stated above, D5290C00003 teaches a pediatric population having a mean weight (+/- SD) of 6.82 (+/- 1.90) kg (which includes children ≥ 5 kg) and receiving nirsevimab (page 16, ¶ 2, lines 15-17) during their first RSV season. D5290C00003 further teaches a pediatric population entering their first and second RSV season (page 14, ¶ 1, lines 2-5).
Regarding claim 53, it is noted that no amendments were introduced to claim 53. As previously explained, the claim recites “the subject weighs ≥ 5 kg and is entering or experiencing their first RSV season and the single fixed dose is 100 mg.” D5290C00003 teaches a pediatric population of mean weight (± SD) of 6.82 (+/- 1.90) kg (which includes children ≥ 5 kg) (page 16, ¶ 2, lines 15-17). D5290C00003 further teaches the pediatric population is entering their first RSV season (page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3). D5290C00003 further teaches the pediatric population receiving a single fixed dose IM of either 10 mg, 25 mg, or 50 mg (page 16, ¶ 2, lines 10-11; page 18, 2.1.2 under “Secondary Objectives,” statement 2).
D5290C00003 does not explicitly teach a single fixed dose of 100 mg.
Zhu et al. teach the administration of a single fixed dose of 50 mg of nirsevimab (MEDI8897) (page 7, column 1, ¶ 1, lines 5-8). Zhu et al. further teaches incorporating the effect of body weight and age of the patient on clearance of the drug into the pharmacokinetic (PK) model to adjust for growth and maturation of infants and predict the concentration of nirsevimab (MEDI8897) in blood serum after a single IM dose for the benefit of enabling once-per season dosing (page 7, column 1, ¶ 1; page 7, column 2, ¶ 1; page 8, fig. 5C).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have modified the method, as previously taught by D5290C00003, in order to have provided the dose of 100 mg in view of the predictive pharmacokinetic (PK) model taught by Zhu et al. for the benefit of enabling once-per season dosing.
One of ordinary skill in the art would have had a reasonable expectation of success for incorporating the effect of body weight and age of the patient to adjust for growth and maturation of infants as taught by Zhu et al. given that the PK model taught by Zhu et al. was developed for palivizumab, another RSV monoclonal IgG1 antibody which targets the highly conserved F glycoprotein of RSV and has been demonstrated to be effective for RSV prevention (Zhu et al. [page1, column 2, ¶ 3, lines 1-4]), and the methods of anti-RSV antibody dosing are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 54, it is noted that no amendments were introduced to claim 54. As previously explained, the claim recites “the subject weighs < 5 kg, is in the first year of life, and is entering their first RSV season, and the single fixed dose is 50 mg.” As previously indicated, D5290C00003 teaches a pediatric population of mean age (± SD) of 6.50 (± 2.64) months (in their first year of life), and of mean weight (± SD) of 6.82 (+/- 1.90) kg (which includes children < 5 kg) (page 16, ¶ 2, lines 15-17). D5290C00003 further teaches the pediatric population entering their first RSV season (page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3). D5290C00003 further teaches the pediatric population receiving a single fixed dose IM of either 10 mg, 25 mg, or 50 mg (page 16, ¶ 2, lines 10-11; page 18, 2.1.2 under “Secondary Objectives,” statement 2).
Regarding claim 57, it is noted that no amendments were introduced to claim 57. As previously explained, the claim recites “…wherein preventing RSV LRTI comprises preventing medically attended RSV-confirmed LRTI or preventing RSV LRTI hospitalization.” As indicated above, D5290C00003 teaches a method of preventing (immunoprophylaxis) respiratory syncytial virus (RSV) lower respiratory tract infection LRTI by administering a single fixed dose of nirsevimab (MEDI8897) in a formulation intramuscularly (IM) to pediatric patients (page 14, lines 2-5; page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3; page 18, 2.1.2 under “Secondary Objectives,” statement 2); D5290C00003 further teaches the incidence of medically attended LRTI (inpatient and outpatient) due to RT-PCR-confirmed RSV over the duration of the 5-month RSV season; and the incidence of hospitalizations due to RT-PCR-confirmed RSV over the duration of the 5-month RSV season as the study primary and secondary endpoints, wherein the study endpoints are objective outcomes or events that are measured to determine if the treatment had an effect. In the instant case, per D5290C00003, medically attended RSV-confirmed LRTI or RSV LRTI hospitalization are outcomes to determine if the method of claim 48 has an effect in preventing RSV LRTI. Therefore, preventing RSV LRTI encompasses preventing medically attended RSV-confirmed LRTI or preventing RSV LRTI hospitalization.
Regarding claim 58, it is noted that no amendments were introduced to claim 58. As previously explained, the claim recites “the method comprises administering the pharmaceutical composition at the beginning of the RSV season.” D5290C00003 teaches Nirsevimab for preventing (immunoprophylaxis) RSV for all infants entering (that is at the beginning of) their first RSV season (page 22, ¶ 3, 3.2.3 under “Rationale for Endpoints,” lines 1-3).
Regarding claim 61, it is noted that no amendments were introduced to claim 61. As previously explained, D5290C00003 further teaches including subjects entering or experiencing their first RSV season who are in the first year of life, (infants had a mean age (± SD) of 6.95 (± 2.63) months) (page 16, ¶ 2), therefore the limitations of claim 61 are already taught by the cited prior art.
Regarding claim 62, it is noted that no amendments were introduced to claim 62. As previously explained, D5290C00003 further teaches including subjects
entering or experiencing their second RSV season and at high risk for severe RSV infection (page 14, ¶ 1, lines 2-5; page 12, ¶ 2, lines 2-4). As previously explained, that RSV seasons have a typical duration of 5 months; in the United States, the RSV season onset ranges from mid-September to mid-November and season offset ranging from mid-April to mid-May (See Zhu et al.). A child entering their second RSV season will be at least 7 months old given that children born at the end of their first RSV season, for example in the month of April, will reach their second RSV season in October of the year of their birth. Therefore, children born after the RSV season offset, for example, in July, will be in their second year of life when they enter or experience their second RSV season. Therefore, the limitations of claim 62 are already taught or suggested by the cited prior art.
Accordingly, claims 48-51, 53, 54, 57, 58, 61, and 62 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
(previous rejection, maintained as to claims 55 and 56, expanded as to claim 63) Claims 55, 56, and 63 are rejected under 35 U.S.C. 103 as being unpatentable over D5290C00003; in view of Zhu et al. as applied to claims 48-54, 57, 58 61 and 62 above; and further in view of Lobo et al. (prior art of record, cited in Applicant’s IDS dated 01/11/2022 as WO 2018/158332 A1).
See claims 55, 56, and 63 as submitted on 09/03/2025.
Regarding claim 55, it is noted that no amendments were introduced to claim 55. As previously explained, neither D5290C00003 and Zhu et al. teach limitations of the pharmaceutical composition outlined in claim 55.
However, Lobo et al. teach a pharmaceutical formulation comprising:
A monoclonal antibody (page 22, column 1, ¶ 0008, 0009)
And ionic excipient which can be lysine or arginine at a concentration of 50 mM to 150 mM (page 22, column 1, ¶ 0010; page 23, column 1, ¶ 0030).
A buffer comprising 10 mM to 50 mM histidine (page 24, column 1, ¶ 0051).
A sugar comprising 100 mM to 140 mM sucrose (page 23, column 2, ¶ 0041; page 24, column 1, ¶ 0050).
A surfactant comprising 0.01 % (w/v) to 0.05% (w/v) polysorbate-80 (page 24, column 1, ¶ 0052; page 28, column 1, ¶ 0129).
The pharmaceutical composition having a pH of 5.5 to 6.5 (page 26, column 2, ¶ 0106).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have included the teachings of Lobo et al. about a pharmaceutical formulation into the method taught by D5290C00003 in view of Zhu et al., for the benefit of providing improved colloidal stability in an antibody formulation.
One of ordinary skill in the art would have had a reasonable expectation of success for providing improved colloidal stability in an antibody formulation as taught by Lobo et al. given that the methods of formulating a pharmaceutical composition are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding amended claim 56 and new claim 63, Lobo et al. further teach:
a) The ionic excipient comprises 80 mM L-arginine hydrochloride (page 26, column 2, ¶ 0112; page 27, column 1, ¶ 0113; page 32, column 2, ¶ 0174).
b) The buffer comprises 30 mM L-histidine, L-histidine hydrochloride, or a combination thereof (page 27, column 1, ¶ 0121; page 32, column 2, ¶ 0174)
c) The sugar comprises 120 mM sucrose (page 23, column 2, ¶ 0041; page 24, column 1, ¶ 0050).
d) The surfactant comprises 0.02% (w/v) polysorbate-80 (page 24, column 1, ¶ 0052; page 28, column 1, ¶ 0129).
e) The pharmaceutical composition having a pH of 5.5 to 6.5 (page 26, column 2, ¶ 0106).
Accordingly, claims 55, 56 and 63 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
(previous rejection, maintained as to claims 59 and 60) Claims 59 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over D5290C00003; in view of Zhu et al.; as applied to claims 48-54, 57, 58 61 and 62 above; and further in view of CCDR Statement. Prior art of record.
See claims 59 and 60 as submitted on 09/03/2025.
As per claims 59 and 60, it is noted that no amendments were introduced to claims 59 and 60. As previously explained, neither D5290C00003 nor Zhu et al. teach administering the pharmaceutical composition in combination with at least one other anti-viral agent.
The CCDR Statement teaches the simultaneous administration of another antiviral agent, an RSV monoclonal IgG1 antibody known as palivizumab, which targets the highly conserved F glycoprotein of RSV: “palivizumab is a passive immunizing agent with a highly specific antigen target (the F glycoprotein of RSV). It therefore does not interfere with the immune response to vaccines and can be administered at the same time at a separate site.” (Page 3, ¶ 5; page 4, ¶ 1; page 7, ¶ 7). It is well known in the art that nirsevimab is also a monoclonal antibody that binds the highly conserved epitope present on the prefusion conformation of the RSV F protein (See Zhu et al.)
Because palivizumab and nirsevimab are functional equivalents, per MPEP 2144.06, their co-administration is prima facie obvious. (“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....).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have modified the method of claim 48 so that the pharmaceutical composition can be administered simultaneously with at least one other antiviral agent, such as palivizumab, as taught by the CCDR Statement, for the benefit of providing a second agent that does not interfere with the immune response of a first vaccine thereby providing adequate RSV protection.
One of ordinary skill in the art would have had a reasonable expectation of success for co-administrating antiviral agents as taught by the CCDR Statement given that the methods of co-administration of antiviral agents to infants are known part of routine clinical practice, are successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claims 59 and 60 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/ patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
(previous rejection, maintained as necessitated by amendment as to claims 48-51, 53-62, expanded as to claim 63) Claims 48-51, 53-63 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15-18 of U.S. Patent No. 12024553 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to a method for preventing RSV LRTI comprising administering the anti-RSV antibody nirsevimab.
See claims 48-51, 53-63 as submitted on 09/03/2025.
Regarding independent claim 48, as indicated above, the amendments introduced and submitted on 09/03/2025 do not include any new limitations. Accordingly, the nonstatutory double patenting previously set forth on 06/04/2025 still applies to the amended claims. As previously explained, both sets of claims are drawn to a method for preventing RSV LRTI comprising administering nirsevimab. Further, both sets of claims encompass the same patient stratification based on patient age, weight, and RSV season. Further, both sets of claims recite identical nirsevimab doses, criteria, and pharmaceutical formulation.
The two sets of claims differ in scope, instant independent claim 48 requires intramuscular administration, while patented claim 1 does not specify route of administration. Additionally, patented claim 1 indicates the exact CRDs of the antibody nirsevimab (also known as MEDI8897) but does not recite “nirsevimab”, while instant claim 48 recites nirsevimab.
Therefore, both sets of claims are not considered patentably distinct from each other.
(previous rejection, maintained as necessitated by amendment as to claims 48-51, 53-62, expanded as to claim 63) Claims 48-51, 53-63 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 20 of copending Application No. 18669241 (reference application), as evidenced by Beyfortus Nonclinical Overview. Dated 12/17/2021 (prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to a method for preventing RSV comprising administering an anti-RSV antibody. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding independent claim 48, as indicated above, the amendments introduced and submitted on 09/03/2025 do not include any new limitations. Accordingly, the nonstatutory double patenting previously set forth on 06/04/2025 still applies to the amended claims. As previously explained, both sets of claims are drawn to a method for preventing RSV comprising administering an anti-RSV antibody. Further, both sets of claims encompass the same patient stratification based on patient age, weight, and RSV season. Further, both sets of claims recite the same doses, criteria, and pharmaceutical formulation.
The two sets of claims differ in scope, instant independent claim 48 requires intramuscular administration of nirsevimab, while patented claim 1 does not specify route of administration, nor the precise antibody. Further, the conflicting claims require a monoclonal antibody with an IC50 of 5.0 ng/ml or less in a neutralization assay of RSV A, or an IC50 of 3.0 ng/ml or less in a neutralization assay of RSV B9320. While instant claims do not recite such limitations, nirsevimab inherently meets those limitations as evidenced by Beyfortus Nonclinical Overview (page 9).
With respect to conflicting claim 14 and the recitation of “AUCo-∞ of greater than 13.4 day-mg/mL”, as evidenced by Beyfortus Nonclinical Overview (page 9), nirsevimab inherently meets this limitation.
Therefore, both sets of claims are not considered patentably distinct from each other.
Response to Arguments
Applicant's arguments filed 09/03/2025 have been fully considered but they are not persuasive.
Applicant contends on page 7 of the Remarks as submitted on 09/03/2025:
“As discussed during the interview held on August 28, 2025, the instant claims are directed to methods of stratifying subjects by weight and/or RSV season and treating those stratified subjects with a single fixed dose of 50 mg, 100 mg, or 200 mg nirsevimab in accordance with the stratification criteria, not the arbitrary dosing of any particular subject. As previously explained, neither D5290C00003 nor Zhu teaches or suggests stratifying subjects into one of three fixed doses based on subject characteristics such as weight and/or RSV season. Instead, and as the Office acknowledges, D5290C00003 refers to the D5290C00002 study, in which subjects were randomized into a dosing regimen of 10 mg, 25 mg, or 50 mg nirsevimab. See, e.g., D5290C00003 at 16, first full paragraph, lines 1-6 and 10-11; see also Domachowske1 at 887, second column, "Study Participants" and Figure 2. This randomized dosing is not the claimed stratified dosing. Zhu does not address this deficiency. Rather, Zhu teaches yet another dosing regimen distinct from that claimed: a one-dose-fits-all dosing approach of "a single fixed 50-mg dose of MED18897 [nirsevimab] for all infants." See Zhu at page 7 (emphasis added). This universal fixed dose was recommended, even though the model used by Zhu accounted for weight (i.e., infants below and above 5 kg) and age (subjects from birth to six months of age). See, e.g., Zhu at page 7, left column. In other words, looking at comparable input parameters to those used by the instant claims to select stratified dosages, Zhu instead teaches a different regimen.”
In response:
The Examiner acknowledges the detailed Remarks submitted by Applicant on 09/03/2025, which have been fully considered. Applicant’s Remarks on page 7 are not persuasive for the following reasons. First, there are two main elements encompassed by the instant claims, the element of stratification and the element of dosing regimens. The D5290C00003 document was cited for providing clear teachings and suggestions that address the stratification element, i.e., teachings and suggestions of patient stratification. Specifically, D5290C00003 teaches pediatric populations having a mean weight (+/- SD) of 6.82 (+/- 1.90) kg (< 5 kg and ≥ 5 kg) and receiving nirsevimab (page 16, ¶ 2, lines 15-17) during their first RSV season. D5290C00003 further teaches passive immunization of a pediatric population at high risk of RSV infection with chronic lung disease (CLD) or congenital heart disease (CHD) entering their first and second RSV season (page 14, ¶ 1, lines 2-5). See above for a full description of the teachings of the D5290C00003 document. It is further noted that methods of preventing RSV in pediatric subjects have been extensively studied as well as stratification or grouping of pediatric subjects (see Jansen et al. 2007, see Domachowske et al. January 2018 and September 2018, see Stockman et al. 2012, see Rose at al. 2018, all of these references were cited in Applicant’s IDS submitted on 01/11/2022). While the D5290C00002 study which was cited in the D5290C00003 document refers to randomization of patients, this teaching was not the teaching cited in the present rejection. The teachings and suggestions cited in the present rejection from the D5290C00003 document and explained above in detail refer to the stratification as recited in instant claims and not to the randomization refer to in the D5290C00002 study. In other words, Applicant’s remarks reproduced above discuss a teaching of stratification that was not relied upon in the instant rejections. Hence, these remarks are unpersuasive.
With respect to second element encompassed by instant claims, namely the dosing regimens. The teachings and suggestions of Zhu et al. cited by Applicant’s remarks and reproduced above also refer to a teaching that was not relied upon in the present rejections. Zhu et al. were cited for teaching a PK model that allows for adjusting the doses to arrive at the claimed dosing regimens by incorporating the effect of body weight and age of the patient on clearance of the drug for the benefit of allowing once-per season dosing. Again, Zhu et al. were not cited for teaching a conclusion or recommendation of a single fixed 50-mg dose of MED18897 [nirsevimab] for all infants. Applicant’s remarks reproduced above as well as those present in the Table of page 10 of the Remarks, do not account for the teachings and suggestions in the Zhu et al. reference which were relied upon in the instant rejections, namely the PK model. Hence, these remarks are unpersuasive.
It is further noted that dosing regiments of RSV drugs, such as nirsevimab and palivizumab have been extensively studied in pediatric patients (See Robbie et al. 2012, see Jansen et al. 2007, see Domachowske et al. January 2018 and September 2018, see Stockman et al. 2012, see Rose at al. 2018, all of these references were cited in Applicant’s IDS submitted on 01/11/2022). As explained above, neither the stratification of subjects, nor models of adjusting doses to formulate dosing regimens, are new in the art. In fact, these elements are well recognized routine elements in the art as well as successfully applied regularly (See Robbie et al. 2012, see Jansen et al. 2007, see Domachowske et al. January 2018 and September 2018, see Stockman et al. 2012, see Rose at al. 2018, all of these references were cited in Applicant’s IDS submitted on 01/11/2022). In view of the forgoing, it is herein maintained that when all of evidence is considered, the totality of the rebuttal Remarks of nonobviousness fail to outweigh the evidence of obviousness. Therefore, in view of the instant claim language, it is maintained that one of ordinary skill in the art would have been motivated and had a reasonable expectation of success in arriving at the claimed invention in view of teachings and suggestions of the cited prior art.
Applicant contends on page 11 of the Remarks as submitted on 09/03/2025:
“Lobo fails to teach or suggest the stratified dosing regimens of the claimed invention, or indeed any dosing regimens based on subject characteristics. A skilled artisan would therefore not arrive at the claimed methods by combining the teachings of D5290C00003 and Zhu with Lobo.”
In response:
Lobo et al. were cited for teaching the exact formulation components as recited in claims 55 and 56, as explained above in detail.
Applicant contends on page 11 of the Remarks as submitted on 09/03/2025:
“The CCDR Statement does not teach or suggest stratified dosing regimens or fixed doses of palivizumab, let alone for another antibody like nirsevimab. Instead, the CCDR Statement discloses a linear, weight-dependent dosing regimen of 15 mg/kg palivizumab. See the CCDR Statement at 6, "Schedule and Dosage." This teaching, to administer pavilizumab to a subject based on an individualized calculation based on their weight, is incompatible with the stratified dosing method (using weight thresholds, not weight-dependent calculations) of the instant claims.”
In response:
As indicated previously, the CCDR statement was cited for demonstrating that palivizumab and nirsevimab can be administered together. The CCDR statement was not cited for teaching stratified dosing regimens or fixed doses. Further, as indicated above, “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.” See MPEP 2144.06 I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE. Further, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have been motivated and had a reasonable expectation of success in combining palivizumab and nirsevimab because they are functional equivalents and both drugs target RSV. Applicant’s remarks reproduced above discuss a teaching of stratification that was not relied upon in the instant rejections. Hence, these remarks are unpersuasive.
Applicant contends on page 12 of the Remarks as submitted on 09/03/2025:
“Claims 48-51 and 53-62 stand rejected on the ground of nonstatutory obviousness-type double patenting over claims 1-13 and 15-18 of U.S. Patent No. 12,024,553. Id. at 18-19 and 27. Applicants respectfully disagree with the rejection. Applicants further note that the instant claims have been amended and the Office has not yet addressed each limitation for every amended claim in the obviousness-type double patenting rejection.”
In response:
A detailed explanation of how both sets of claims are not considered patentably distinct from each other, which addresses the limitations of instant claims is provided above. Note that this is not an obviousness-type double patenting rejection.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672