Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/13/2026 has been entered.
Status of the Claims
2. Claims 1-5 are the original claims filed on 6/18/2025. IN the Response of 10/29/2025, claims 1, 3 and 5 are amended. In the Response of 3/13/2026, claims 1 and 5 are amended and new claims 6-30 are added.
Claims 1-30 are the claims under examination.
This Office Action contains new grounds for rejection.
Priority
3. USAN 19/242,715, filed 06/18/2025, and having 1 RCE-type filing therein, is a Continuation of 18/150,514, filed 01/05/2023, now U.S. Patent # 12404335, 18/150,514 is a Continuation of 17/822,978, filed 08/29/2022, now U.S. Patent # 11548951, 17/822,978 is a Continuation of 17/501,362, filed 10/14/2021, now abandoned, 17/501,362 Claims Priority from Provisional Application 63/261,742, filed 09/28/2021, 17/501,362 Claims Priority from Provisional Application 63/260,130, filed 08/10/2021, 17/501,362 Claims Priority from Provisional Application 63/201,978, filed 05/21/2021, 17/501,362 Claims Priority from Provisional Application 63/091,839, filed 10/14/2020.
Information Disclosure Statement
4. As of 3/30/2026, a total of three (3) IDS are filed for this application: 10/6/2025; 10/10/2025; and 3/13/2026. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Rejections
Double Patenting
5. The provisional rejection of Claims 1-5 on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 4, 27-29, 31, 51, and 56 of copending Application No. 18/827,383 (reference application US 20250099583) is withdrawn.
The terminal disclaimer filed on 3/13/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 18/827,383 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Rejections Maintained
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
6. The rejection of Claim(s) 1-2 and 4-5 under 35 U.S.C. 103 as being unpatentable over Guelberto et al (Oncogene 28(34):3008-3021(8/27/2009)) in view of Hartmann et al (US US 20160159894-A1) as evidenced by Burak (US 20220088231) is maintained.
Applicants’ response is improper and incomplete.
a) Applicant’s arguments with respect to claim(s) 1-5 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Applicants rely on a prior art reference (“Sherman; US 20210253719) cited in sister application 19/242,725 that has not been raised in the prosecution proceeding for the instant application.
b) Applicant refers to an affidavit or declaration filed in the prior application.
Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of the prior application do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make the remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Applicants rely on 1.132 declaration evidence (Bedian affidavit) from sister Application No. 19/242,725. No copy of the declaration is provided in any of the IDS on file for the instant application.
The rejections set forth from the Office Action of 11/13/2025 remain as follows:
“A) Applicants allege there is no motivation to use much less extend the ½ life of the AVE1642 antibody citing Exhibit A (Chen teaches AVE1642 was a clinical trial discontinued for lack of efficacy shown in Table 1), Exhibit B (TCD10631 Synopsis teaches no significant efficacy) and Exhibit C (TED6421 teaches the main reason to discontinue the study was disease progression (study part 1)).
Response to Arguments
Clinical trials may be discontinued for several reasons, including safety concerns, futility, or the demonstration of early benefit or harm. Other common reasons include insufficient patient enrollment, lack of funding, business decisions by the sponsor, or significant problems with the trial's protocol or procedures.
Ethical and scientific reasons
Safety: The intervention causes unexpected or serious adverse events that put participants at risk.
Efficacy/Benefit: A trial may end early if a treatment is found to be significantly more effective than the control, making it unethical to withhold the treatment from the control group.
Futility: The trial may be stopped if early analysis shows the treatment is unlikely to prove effective, or if there is no hope of achieving a significant difference between groups.
Operational and logistical reasons
Recruitment failure: A common reason is difficulty in enrolling enough participants to meet the trial's goals.
Funding issues: Insufficient funding is a major cause of trial discontinuation.
Sponsor-related reasons: A company might discontinue a trial for business reasons, such as prioritizing a different drug, changing its strategy, or facing financial difficulties.
Protocol or procedural issues: Substantial changes to the study protocol or problems with trial procedures can also cause a trial to be halted.
AS regards Chen, the publication is dispositive to Applicants assertion because there is no disclosure for the rationale(s)/reason(s) for the AVE1642 trial being discontinued in the reference. There is no mention of efficiency in the Chen reference.
AS regards the TCD10631 Synopsis, the report is dispositive to Applicants assertion and states on p. 1 that efficiency was NOT a determining factor in the discontinuation of the trial:
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, and on p. 9 that the conclusion of the study is “Not disclosed.”
As regards TED6421, the report is dispositive to Applicants assertion and states on p. 1 that efficiency was NOT a determining factor in the discontinuation of the trial:
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, and on p. 12 that the conclusion of the study is “Not disclosed.”
No where in Exhibits A-C, and that Applicants rely on as authority for their case-in-chief, is there an explicit or implicit disclosure that the trial(s) for AVE1642 was ineffective and therefore discontinued. The POSA could reasonably conclude the references would NOT deter the motivation to re-examine AVE1642 under any other context much less having a modified Fc region. It is entirely unclear how Applicants have drawn their conclusions from Exhibits A-C.
B) Applicants allege there is no motivation in Guelberto to indicate that a longer ½ life would improve AVE1642’s “inferior efficacy in cancer treatment” (9 days, Table 1 and pp. 2-6) as compared to MK0646 (approx. 4 days), where instead, Guelberto supports shorter ½ lives are clinically promising.
Response to Arguments
i) Guelberto teaches different anti-IGF-IR antibodies having different half-lives from amongst each other:
“It is also noteworthy that the effective half-lives of the anti-IGF-IR antibodies differ from each other. The half-life of CP751,871 (IgG2) of approximately 20 days seems longer than others (Baserga et al., 2003; Dong et al., 2007). Half-life estimates of 4 days (Atzori et al., 2008), 6 days (Leong et al., 2007), 7–11 days (Tolcher et al., 2007) and 9 days (Higano et al., 2007) were reported, respectively, for MK0646, R1507, AMG-479 and A12 (Table 1). These differences could be explained in part by antibody backbone, but may also reflect target mediated disposition at low doses (Goodin, 2008).”
Data shown for AVE6412 in Table 1 is for “*Estimated half-life and dosing schedule.”
Guelberto teaches the AVE1642 half-life was estimated to be approximately 9 days, however, Guelberto does not qualify/define the meaning of terms “estimate” and “approximately” in its entire disclosure for AVE1642 or MK0646.
“estimate”: the instant specification does not define the term in order to ascertain the breadth and scope as could be applied to the reference.
“approximate”: the specification does not define the term in order to ascertain the breadth and scope as could be applied to the reference.
The POSA cannot reasonably ascertain what the standard deviation for the ½ life is between AVE1642 and MK0646 form the limited disclosure.
ii) No where does Guelberto provide explicit or implicit teaching that AVE1642 is “inferior” in its efficacy. The paragraph dedicated to AVE1642 on p. 3011, Col. 2 is silent of any qualification towards the efficacy of the antibody. Dispositive to Applicants allegations that AVE1642 is inferior in efficacy is that Guelberto does NOT disparage the efficacy of any clinical trials for the IGF-1R antibodies:
“Early clinical trials of IGF-IR-targeting agents have been encouraging enough to justify expanded clinical trial programs. Pharmacodynamic evidence that antiIGF-IR antibodies reduce receptor signaling is strong. Safety profiles, at least for short- and medium-term treatment durations, are favorable. It is too early to reach conclusions on efficacy” (p. 3017, Conclusions, Col. 2).
It is entirely unclear how Applicants have drawn any conclusions from Guelberto that AVE1642 has an “inferior efficacy in cancer treatment” much less for any other clinical applications.
C) Applicants allege Hartmann discourages targeting eye diseases using anti- IGF-IR antibodies with an extended half-life using an Fc region YTE.
Response to Arguments
Despite Applicants allegation of the benefits of the lower ½ life for MK0646 compared with AVE1642, Hartmann teaches the caveats of low ½ life IGF-R1 antibodies such as Fab fragments for use in treating ocular disease at
[0008] Typically for ocular diseases via intravitreal application smaller antibody fragments like Fab or Fab2 are often used as they have a low serum half-life and the risk of systemic toxicities is lower. However, this smaller fragments typically have also lower intravitreal half-lives (e.g. due to the faster diffusion into serum) and have to be dosed typically more often.
Hartmann specifically recommends higher ½ life antibodies for ocular uses at
[0255] In some cases antibodies with reduced half-life in the blood circulation are desired. For example, drugs for intravitreal application should have a long half-live in the eye and a short half-life in the circulation of the patient. Such antibodies also have the advantage of increased exposure to a disease site, e.g. in the eye.
The teaching of Hartmann is unequivocal that longer ½ life for an anti-IGF-R1 antibody is beneficial in treating eye diseases. It is entirely unclear how Applicants have drawn any conclusions from Hartmann that a short ½ life for an IGF-R1 antibody is preferable for ocular disease therapy.
D) Applicants allege no reasonable expectation of success could be envisaged by YTE-modification of AVE1642 that maintains its activity citing Exhibit D (Majumdar) and Exhibit E (Thorpe) because the expectation is that the modified antibody would lose both binding affinity to and inhibitory effect on autophosphorylation of IGF-R1.
Response to Arguments
See Ex parte Murphy and Burford (217 USPQ 479 (BPAI 1982)) stating in part:
"The determination that a reference is from a non-analogous art is therefore two-fold. First, we decide if the reference is within the field of the inventor's endeavor. If it is not, we proceed to determine whether the reference is reasonably pertinent to the particular problem with which the inventor was involved."
AS regards Majumdar, Majumdar does not teach or suggest modifying an IGF-R1 antibody to express a YTE mutation. Majumdar does not teach or suggest the AVE1642 antibody much less the IGF-R1 antibodies mentioned in Guelberto for their “estimated” and/or “approximate” ½ lives. Majumdar does not teach or suggest the use of YTE mutated IgG1 antibody for use in vitreous/ocular/eye treatment(s). The citation of Majumdar begs the question of how the reference relates to generating YTE-modified Fc constant regions for the AVE1642 antibody.
AS regards Thorpe, Thorpe does not teach or suggest modifying an IGF-R1 antibody to express a YTE mutation. Thorpe does not teach or suggest the AVE1642 antibody much less the IGF-R1 antibodies mentioned in Guelberto for their “estimated” and/or “approximate” ½ lives. Thorpe does not teach or suggest the use of YTE mutated IgG1 antibody for use in vitreous/ocular/eye treatment(s). The citation of Thorpe begs the question of how the reference relates to generating YTE-modified Fc constant regions for the AVE1642 antibody.
Taken together and in view of the foregoing arguments and observations, the rejection of the claims is maintained.
12. The rejection of Claim(s) 1-5 rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al (Clin Cancer Res. 2009 April 15; 15(8): 2840–2849) in view of Guelberto et al (Oncogene28(34):3008-3021(8/27/2009)) and Hartmann et al (US US20160159894-A1) as evidenced by Burak (US 20220088231) is maintained.
A) Applicants allege there is no motivation to use much less extend the ½ life of the AVE1642 antibody citing Exhibit A (Chen teaches AVE1642 was a clinical trial discontinued for lack of efficacy shown in Table 1), Exhibit B (TCD10631 Synopsis teaches no significant efficacy) and Exhibit C (TED6421 teaches the main reason to discontinue the study was disease progression (study part 1)).
Response to Arguments
Clinical trials may be discontinued for several reasons, including safety concerns, futility, or the demonstration of early benefit or harm. Other common reasons include insufficient patient enrollment, lack of funding, business decisions by the sponsor, or significant problems with the trial's protocol or procedures.
Ethical and scientific reasons
Safety: The intervention causes unexpected or serious adverse events that put participants at risk.
Efficacy/Benefit: A trial may end early if a treatment is found to be significantly more effective than the control, making it unethical to withhold the treatment from the control group.
Futility: The trial may be stopped if early analysis shows the treatment is unlikely to prove effective, or if there is no hope of achieving a significant difference between groups.
Operational and logistical reasons
Recruitment failure: A common reason is difficulty in enrolling enough participants to meet the trial's goals.
Funding issues: Insufficient funding is a major cause of trial discontinuation.
Sponsor-related reasons: A company might discontinue a trial for business reasons, such as prioritizing a different drug, changing its strategy, or facing financial difficulties.
Protocol or procedural issues: Substantial changes to the study protocol or problems with trial procedures can also cause a trial to be halted.
AS regards Chen, the publication is dispositive to Applicants assertion because there is no disclosure for the rationale(s)/reason(s) for the AVE1642 trial being discontinued in the reference. There is no mention of efficiency in the Chen reference.
AS regards the TCD10631 Synopsis, the report is dispositive to Applicants assertion and states on p. 1 that efficiency was NOT a determining factor in the discontinuation of the trial:
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, and on p. 9 that the conclusion of the study is “Not disclosed.”
As regards TED6421, the report is dispositive to Applicants assertion and states on p. 1 that efficiency was NOT a determining factor in the discontinuation of the trial:
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, and on p. 12 that the conclusion of the study is “Not disclosed.”
No where in Exhibits A-C, and that Applicants rely on as authority for their case-in-chief, is there an explicit or implicit disclosure that the trial(s) for AVE1642 was ineffective and therefore discontinued. The POSA could reasonably conclude the references would NOT deter the motivation to re-examine AVE1642 under any other context much less having a modified Fc region. It is entirely unclear how Applicants have drawn their conclusions from Exhibits A-C.
B) Applicants allege there is no motivation in Zeng to indicate that a longer ½ life would improve AVE1642’s activity because Zeng does not use a monotherapy and “before it became well understood in the art that AVE1642 was an ineffective therapeutic antibody” (citing Chen, TED6421 synopsis).
Response to Arguments
AS discussed herein above under section (A) for Chen and the TED6421 synopsis, the disclosures are dispositive to Applicants allegation of the inefficacy for the AVE1642 antibody. The Chen and the TED6421 synopsis do not teach or suggest that an AVE1642 monotherapy is inefficacious. Applicants are reminded that neither of Chen and the TED6421 synopsis offer any conclusions on the efficacy of the AVE1642 clinical trial.
AS regards Zeng’s alleged teaching lower doses for AVE1642 and no motivation for extending the ½ life, Zeng teaches EM164, a full antagonistic anti-IGF1R antibody, did not stimulate IGF1R autophosphorylation (in other words inhibits), but down-regulated IGF1R in vitro and in vivo.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, 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, Zeng teaches “Because antibodies have a very long half-life in vivo, we next explored whether low doses of antibody would allow IGF1R to recover over the course of a week. Mice bearing two xenograft tumors implanted in the mammary fat pad of opposite sides were studied. When xenograft tumors were formed, mice were treated with varying doses of AVE1642by i.p. injection. Tumors were removed from mice at 2 and 7 days after AVE1642 treatments. Figure 6A shows that all doses of AVE1642 suppressed IGF1R levels at 2 days after treatment. Low doses of antibody (25 and 50 Ag/mouse) allowed IGF1R to recover to pretreatment levels at 7 days.” Accordingly, Zeng recognized that recovery of IGF1R function was recurrent after a short exposure to the AVE1642 despite the longer ½ life associated with antibodies in general. Zeng does not teach, per se, what the ½ life is AVE1642, but a short exposure to the antibody results in a rapid recovery of IGF-R1 activity.
In addition, Zeng is cited in combination with Guelberto. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
C) Applicants allege Hartmann discourages targeting eye diseases using anti- IGF-IR antibodies with an extended half-life using an Fc region YTE.
Response to Arguments
Despite Applicants allegation of the benefits of the lower ½ life for MK0646 compared with AVE1642, Hartmann teaches the caveats of low ½ life IGF-R1 antibodies such as Fab fragments for use in treating ocular disease at
[0008] Typically for ocular diseases via intravitreal application smaller antibody fragments like Fab or Fab2 are often used as they have a low serum half-life and the risk of systemic toxicities is lower. However, this smaller fragments typically have also lower intravitreal half-lives (e.g. due to the faster diffusion into serum) and have to be dosed typically more often.
Hartmann specifically recommends higher ½ life IGF-R1 antibodies for ocular uses at
[0255] In some cases antibodies with reduced half-life in the blood circulation are desired. For example, drugs for intravitreal application should have a long half-live in the eye and a short half-life in the circulation of the patient. Such antibodies also have the advantage of increased exposure to a disease site, e.g. in the eye.
The teaching of Hartmann is unequivocal that longer ½ life for an anti-IGF-R1 antibody is beneficial in treating eye diseases. It is entirely unclear how Applicants have drawn any conclusions from Hartmann that a short ½ life for an IGF-R1 antibody is preferable for ocular disease therapy.
D) Applicants allege no reasonable expectation of success could be envisaged by YTE-modification of AVE1642 that maintains its activity citing Exhibit D (Majumdar) and Exhibit E (Thorpe) because the expectation is that the modified antibody would lose both binding affinity to and inhibitory effect on autophosphorylation of IGF-R1.
Response to Arguments
See Ex parte Murphy and Burford (217 USPQ 479 (BPAI 1982)) stating in part:
"The determination that a reference is from a non-analogous art is therefore two-fold. First, we decide if the reference is within the field of the inventor's endeavor. If it is not, we proceed to determine whether the reference is reasonably pertinent to the particular problem with which the inventor was involved."
AS regards Majumdar, Majumdar does not teach or suggest modifying an IGF-R1 antibody to express a YTE mutation. Majumdar does not teach or suggest the AVE1642 antibody much less the IGF-R1 antibodies mentioned in Guelberto for their “estimated” and/or “approximate” ½ lives. Majumdar does not teach or suggest the use of YTE mutated IgG1 antibody for use in vitreous/ocular/eye treatment(s). The citation of Majumdar begs the question of how the reference relates to generating YTE-modified Fc constant regions for the AVE1642 antibody.
AS regards Thorpe, Thorpe does not teach or suggest modifying an IGF-R1 antibody to express a YTE mutation. Thorpe does not teach or suggest the AVE1642 antibody much less the IGF-R1 antibodies mentioned in Guelberto for their “estimated” and/or “approximate” ½ lives. Thorpe does not teach or suggest the use of YTE mutated IgG1 antibody for use in vitreous/ocular/eye treatment(s). The citation of Thorpe begs the question of how the reference relates to generating YTE-modified Fc constant regions for the AVE1642 antibody.
Taken together and in view of the foregoing arguments and observations, the rejection of the claims is maintained.
The rejection is maintained.
New Grounds for Rejection
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
7. Claim(s) 1-2, 4-5, 7-10, 14-20, and 26-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sherman et al. (US 20210253719, published 19 August 2021, filed 3 March 2021 and corresponding to Sherman et al. (WO 2021/041773, published 04 March 2021, filed 28 August 2020; IDS 10/6/2025) as evidenced by Burak et al. (U.S. Patent No. 10,093,741; IDS 10/6/2025) and in view of HARTMANN et al (AU 2019200635; published 2019-02-21) as evidenced by Viridian (News Release VRDN-003, pp. 1-4 (6/11/2024)).
Claim interpretation
VRDN-1100, VRDN-001 and AVE1642 correspond to the same anti- IGF-1R inhibitor antibody.
The claimed method invention is prima facie obvious over Sherman as evidenced by Burak in view of Hartmann as evidenced by Viridian.
As regards claims 1 and 5, Sherman discloses an IGF-1R inhibitor such as the antibody AVE1642 ([0057; 0062; 0098; 0099; 0201; 0229; Example 4) in a pharmaceutical composition to treat TED ([0165-166].
Sherman teaches a VH of SEQ ID NO: 78 that corresponds to instant SEQ ID NO: 14:
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Sherman teaches a VL of SEQ ID NO: 80 that corresponds to instant claimed SEQ ID NO: 13:
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Instant claim 2 and 17 recites the VRDN-1100 VL domain (SEQ ID NO: 13) that is identical to the AVE1642 VL domain (SEQ ID NO: 14) as taught in Burak:
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Instant claim 2 and 17 recite the VRDN-1100 VH domain (SEQ ID NO: 14) that is identical to the AVE1642 VH domain (SEQ ID NO: 8) as taught in Burak:
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The disclosure of the AVE1642 clone in the WO PCT application that shares identity with the instant claimed VDRN-1100 CDR1-3 sequences, renders those sequences inherent to the filing date of the WO PCT reference. Sherman WO PCT is effective prior art.
As regards claim 5, Sherman teaches the use the AVE1642 antibody in TED therapies as a pharmaceutical composition. See, for example, the specific citation and reference to the AVE1642 antibody taught throughout Sherman PCT.
Embodiment 57. The method of Embodiment 42 wherein the antibody is AVE1642.
[078] Embodiment 58. The method of Embodiment 57 wherein the AVE1642 is dosed at: a) 1-60 mg/kg or 75-4500 mg IV every 3 weeks; or b) 0.6-40 mg/kg or 45-3000 mg IV every 2 weeks; or c) 0.3-20 mg/kg or 22-1500 mg IV weekly.
[0122] Embodiment 100. The pharmaceutical composition of Embodiment 92, wherein the IGF-1R inhibitor is AVE1642, formulated for administration: a) 1-60 mg/kg or 75-4500 mg IV every 3 weeks; or b) 0.6-40 mg/kg or 45-3000 mg IV every 2 weeks; or c) 0.3-20 mg/kg or 22-1500 mg IV weekly.
[062] Embodiment 42. The method of Embodiment 40 wherein said antibody is chosen from ganitumab, figitumumab, MEDI-573, cixutumumab, dalotuzumab, robatumumab, AVE1642, BIIB022, xentuzumab, and istiratumab-----.
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As regards clams 1 and 5 and as evidenced by Viridian (News Release VRDN-003, pp. 1-4 (6/11/2024)) teaches VRDN-001 is a full antagonist of IGF-1R, which would necessarily encompass inhibiting autophosphorylation.
AS regards claim 1 and 5, Hartmann teaches specific mutations for Fc extending half-life of anti-IGF1-R antibodies through modification of the Fc domain to promote FcRn interaction by M252Y, S245Y and T256E (YTE). Figure 20 bolus application of 10 mg/kg into huFcRn transgenic male C57BL/6J mice +/- 276: AUC data for wild-type IgG as well as YTE and IHH-AAA Fc-modified IgGs; b) BIAcore sensorgram; c) FcRn affinity column elution; wild-type anti-IGF-lR antibody (reference), YTE-mutant of anti-IGF1R antibody, IHH-AAA-mutant of anti-IGF-lR antibody. Change of retention time in an FcRn affinity chromatography depending on the number of mutations introduced into the Fc-Region.
AS regards claims 4, 7, 14-16, and 26-30 and ss evidenced by Viridian, the extension of the half-life for an Fc-modified anti-IGF-1R comprising the antigen binding domains of VRDN-001 for TED is motivated “to preserve the compelling IGF-1R clinical response we have seen in our earlier proof-of-concept studies of VRDN-001.” The increase in half life being increased compared to teprotumumab is relative and not defined by how the activity is measured much less a metric for an increase.
AS regards claim 8-10, Sherman discloses the antibody AVE1642, which as evidenced by Burak corresponds to instant SEQ ID NO: 93 for a light chain, respectively, and that are inherent to AVE1642. Burak discloses SEQ ID NO: 9 for the anti-IGF-1R antibody AVE1642. See column 28. This antibody is formed by fusing instant SEQ ID NO: 13 (amino acids 1-219 of SEQ ID NO: 9) to instant SEQ ID NO: 14 (amino acids 220-673 of SEQ ID NO: 9). See at least column 28 and SEQ ID NOS: 1-9.
AS regards claim 1, 5, 10 and 20, Hartmann as evidenced by Viridian teaches and suggests the introduction of M252Y, S245Y and T256E (YTE) into the Fc region of the VRDN-001 antibody heavy chain of SEQ ID NO: 94 (comparison of SEQ ID NO: 92 (native) vs SEQ ID NO: 94 (Fc half-life extension mutations):
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The combined reference teachings provide explicit use of the VRDN-1100 or VRDN-001 or AVE1642 anti- IGF-1R inhibitor antibody comprising a mutated Fc region to extend the half-life for the anti-IGF-R1 that comprises M252Y, S254T, and T256E (YTE) substitutions. Because the antibody is established for use in TED therapy, and the sequence and functional properties for the claimed antibody are well established in the art, the POSA could predict with a reasonable degree of success that the mutation of a limited number of Fc domain residues taught as candidates by two separate references with limited number of amino acid substitutions for each of those residues could yield an extended half-life for the antibody.
The claims are prime facie obvious where the distinction in the making and the using of the method invention is based on the same antibody clone of the reference art but under a different assumed name.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
8. Claims 3, 6, 11-13, and 21-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 3, 6, 11-13, and 21-25 depend from generic claims defined by LCDR1-3, HCCDR1-3, a Fc mutated domain comprising YTE, inhibition of autophosphorylation of IGF-1R, and being unlimited and silent as to what antigen the antibody actually binds, e.g., see Chen et al. (PTO 892) teaching antibodies that prevent IGF ligands from activating the receptor). Moreover, each of the claims is required to have an IC50 of < to 0.4 nM without limitation as to what the antibody is inhibitory to or for. Still further, the range “< to 0.4 nM” is infinite in scope.
The specification does not support the infinite genus of antibodies that meet the full scope of the claims. (MPEP 706.03(m) states in part "New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.”)
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.
9. Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19/242,725 (reference application US 20250382374).
As regards claims 1-30: the ref species of SEQ ID NOs: 93 and 94 the light chain and the heavy chain, respectively, of the VRDN-1100 (anti-IGF-IR) clone anticipate and/or render obvious the instant claimed sequences of SEQ ID NO: 13 and 14 comprising identical corresponding VLVH domains; the ref species of SEQ ID NOs: 93 and 94 the light chain and the heavy chain, respectively, of the VRDN-1100 (anti-IGF-IR) clone anticipate and/or render obvious the instant claimed sequences of SEQ ID NO: 93 and 94 comprising identical light and heavy chains.
the ref teaches and claims an Fc of for the sequence of SEQ ID NO: 94 comprising the substitutions M252Y, S254T, and T256E (within the sequence of SEQ ID NO: 92):
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. US 12404337. Although the claims at issue are not identical, they are not patentably distinct from each other because the claim sets encompass the VH/VL CDR1-3 and VH/VL domains for the anti-IFR-R1 antibody clone (VRDN-1100 or VRND-001 (or AVE1642 or EM164)) that comprises: a light chain variable region having the amino acid sequence of SEQ ID NO: 13 that corresponds to ref SEQ ID NO: 2; a heavy chain variable region having the amino acid sequence of SEQ ID NO: 14 that corresponds to ref SEQ ID NO: 3; a heavy chain of SEQ ID NO: 92 that corresponds to ref SEQ ID NO: 10; a light chain of SEQ ID NO: 93 that corresponds to ref SEQ ID NO: 11.
Conclusion
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643