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
Applicant’s election without traverse of Group I, claims 1-3, 9, 10, 22, 23, 42, and 60 in the reply filed on 09/15/2025 is acknowledged. Applicant further elected an anti-CD33 antibody comprising the HCDRs 1-3 of SEQ ID NO(s): 14, 7, and 8, respectively, and the LCDRs 1-3 of SEQ ID NO(s): 22-24, respectively. The elected CDRs are comprised within the heavy chain variable region (VH) of SEQ ID NO: 13 and the light chain variable region (VL) of SEQ ID NO(s): 21, 25, and 29 (claim 2). The elected CDRs are also comprised within 1) the heavy and light chains of SEQ ID NO(s): 39 and 37 (claims 9 and 10) and 2) the amino acid sequences of SEQ ID NO(s): 97-108 (claim 42).
Claims 1-3, 9, 10, 19, 21-23, 28, 31, 33, 36, 37, 42, 43, 45, 46, 48, and 60 are pending.
Claims 19, 21, 28, 31, 33, 36, 37, 43, 45, 46, and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/15/2025.
Claims 1-3, 9, 10, 22, 23, 42, and 60 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-3, 9, 10, 19, 21-23, 28, 31, 33, 36, 37, 42, 43, 45, 46, 48, and 60 have an effective filing date of 06/26/2019, corresponding to PRO 62/867,032.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/22/2021, 03/30/2023, 06/21/2023, and 04/08/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Notes on the Prior Art
As indicated above Applicant has elected an anti-CD33 antibody comprising the HCDRs 1-3 of SEQ ID NO(s): 14, 7, and 8, respectively, and the LCDRs 1-3 of SEQ ID NO(s): 22-24, respectively. At the effective filing date of the invention, anti-CD33 antibodies were known in the art. For example Rosenblum (US PAT 6,599,505, issue date: 07/29/2003) teach the treatment of CD33-expressing tumor cells using immunotoxins that comprise a cell growth modulator and an anti-CD33 targeting antibody. See Abstract. Furthermore Bachmann et al. (US PG PUB 2012/0251554, publication date: 10/04/2012) teach antibodies specific for the tumor antigen CD33, as well as the use of anti-CD33 antibodies for the immunotargeting of CD33-expressing cancer cells. Following a sequence search, it has been determined that the prior art does not teach or suggest an anti-CD33 antibody comprising the HCDRs 1-3 of SEQ ID NO(s): 14, 7, and 8, respectively, and the LCDRs 1-3 of SEQ ID NO(s): 22-24, respectively. The instantly claimed anti-CD33 antibody is also not an obvious variant of any art-known anti-CD33 antibodies. Therefore the elected anti-CD33 antibody comprising the HCDRs 1-3 of SEQ ID NO(s): 14, 7, and 8, respectively, and the LCDRs 1-3 of SEQ ID NO(s): 22-24, respectively, is free of the prior art.
Claim Rejections
35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Regarding claims 1-3, 9, 22, 23, and 60, the term “optionally” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 10 and 42 are included in this rejection, because these claims depend from claim 9.
Claim Rejections
35 U.S.C. 112(a)
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.
Claims 1, 3, 9, 22, 23, and 42 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1(a) is drawn to an anti-CD33 antibody comprising one of four different HCDR combinations. Three of said HCDR combinations results in a VH that is capable of binding CD33 when paired with the LCDRs of claim 1(b), according the Table at p. 33 of the specification. One of the potential anti-CD33 antibody HCDR combinations, however, is the HCDR1 of SEQ ID NO: 14, the HCDR2 of SEQ ID NO: 11, and the HCDR3 of SEQ ID NO: 8 (identical to SEQ ID NO(s): 12 and 16), and there is no evidence in the specification that this HCDR combination results in a VH that is capable of binding CD33 when paired with the LCDRs of claim 1(b). This HCDR combination does not satisfy the written description requirement, because absent empirical determination one skilled in the art would be unable to determine whether the HCDR combinations that comprises the HCDR1 of SEQ ID NO: 14, the HCDR2 of SEQ ID NO: 11, and the HCDR3 of SEQ ID NO: 8 (identical to SEQ ID NO(s): 12 and 16) is capable of binding CD33 when paired with the LCDRs of claim 1(b).
Claims 3 and 22 are included in this rejection, because these claims depend from claim 1 but do not cure the deficiencies of claim 1 with respect to 35 U.S.C. 112(a).
Claim 9 recites a genus of anti-CD33 heavy and light chain combinations. Following a review of the specification, it appears that 15 species within said genus have been described, see the heavy and light chain pairs recited in claim 10. Even though Applicant has disclosed 15 species within the claimed genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which heavy and light chain combinations give rise to antibody molecules capable of binding CD33. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed 15 species within the genus claimed; however given the substantial antibody structure variation within the genus as well as the high level of unpredictability in the art, the disclosure of said 15 species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences that confer upon an antibody the ability to bind CD33, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind CD33. Absent a description of the at least minimal structural features correlating with a functional ability to bind CD33 which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences may be combined such that the resultant heavy and light chains comprise six CDRs that confer the ability to bind CD33.
It is further noted that claim 9 recites heavy and light chain variants comprising one or more conservative amino acid substitutions, which allows for variability within the heavy and light chain CDRs. While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example in a series of experiments involving a monoclonal antibody to Legionella pneumophilia serotype 1, McCarthy et al. (J. Immunol. Methods, 251(1-2): 137-149, 2001) demonstrated that a single VH CDR3 substitution of tyrosine to serine at position 95 resulted in the total loss of antigen recognition in an ELISA. Lin et al. (African Journal of Biotechnology, 10(79):18294-18302, 2011) teach that a single amino acid substitution in the VL CDR3 of an anti-avian infectious bronchitis virus (IBV) single-chain antibody (ZL.80) may abrogate binding. For example at Figure 3, Lin et al. demonstrate that replacing either the Cys105 or Asp106 residue in the VL CDR3 of ZL.80 with an alanine residue reduces binding to near negative control levels. Lin et al. also teach that some single amino acid substitutions in the VL CDR3 of ZL.80 may significantly improve binding. For example replacing the Val108 residue in the VL CDR3 of ZL.80 with a tyrosine residue results in a 12.9-fold increase in affinity compared to parental ZL.80. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues of the heavy and light chains of claim 9 could be changed such that the resultant variant CDR residues form an antigen-binding site capable of binding CD33. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general, guidance is needed. Since the disclosure fails to describe relevant, identifying structural characteristics, in the form of heavy and light chain CDR amino acid sequences, that correlate with the ability to bind CD33, and because the 15 disclosed species detailed above are not sufficient to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Although screening techniques can be used to isolate CDR variant heavy and light chains that possess the ability to bind CD33, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Claims 23 and 42 are included in this rejection, because these claims depend from claim 9 but do not cure the deficiencies of claim 9 with respect to 35 U.S.C. 112(a).
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed anti-CD33 antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642