Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED CORRESPONDENCE
Election/Restrictions
2. Applicant’s election without traverse of Group I, claims 1-4 and 7, in the reply filed on 24 November 2025 is acknowledged. Applicant’s election of antibody 1B7, having a variable light chain of SEQ ID NO: 92 (CDRs of SEQ ID NOs: 93, 94 and 95) and a variable heavy chain of SEQ ID NO: 97 (CDRs: SEQ ID NOs: 98, 99 and 100), as the species of antibody that binds CD123 in the reply filed on 24 November 2025 is also acknowledged. Claims 9, 11, 14-17 and 20-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07 August 2025.
Status of Application, Amendments, and/or Claims
3. The Response filed on 24 November 2025 has been entered in full. Claims 9, 11, 14-17 and 20-28 have been withdrawn as discussed supra. Therefore, claims 1-4, 7, 9, 11, 14-17 and 20-28 are pending, and claims 1-4 and 7 are the subject of this Office Action.
Improper Markush
4. Claims 1-2 are rejected (and dependent claims 3-4 and 7 are also rejected) on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
5. In the instant case, the Markush grouping of antibodies which bind CD123 recited in claims 1-2 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the various antibodies have different amino acid sequences and/or different chemical structures, and thus share no structural similarity. Therefore, there is no substantial common structural feature and a common use that flows from the substantial structural feature.
6. To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112 (Written Description)
7. 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.
8. Claims 1-4 and 7 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.
9. The claims are drawn quite broadly to an antibody or antigen binding derivative thereof that binds to an extracellular domain of interleukin-3 (IL-3) receptor a-chain (CD 123), and comprises a light chain variable (VL) domain and a heavy chain variable (VH) domain, wherein: the VL domain comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:93, a VL-CDR2 having a sequence set forth in SEQ ID NO:94, and a VL-CDR3 having a sequence set forth in SEQ ID NO:95; and the VH domain comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:98, a VH-CDR2 having a sequence set forth in SEQ ID NO:99, and a VH-CDR3 having a sequence set forth in SEQ ID NO: 100. The claims also recite wherein the antibody or antigen binding derivative thereof comprises: (i) a VL domain comprising an amino acid sequence with at least about 80% identity to the sequence set forth in one of SEQ ID NOS: 2, 12, 22, 32, 42, 52, 62, 72, 82, 92, 102, 112, 122, 132, 142, 171, and 179; and (ii) a VH domain comprising an amino acid sequence with at least about 80% identity to the sequence set forth in one of SEQ ID NOS: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, 127, 137, 147, 175, and 183. It is noted that the recitation “a sequence set forth in SEQ ID NO:93”, for example, can be interpreted to mean a partial sequence comprising as few as 2 amino acids of SEQ ID NO: 93. Thus the claims are drawn to a large genus of antibodies or antigen binding derivatives that binds to an extracellular domain of CD123 that are only defined by a very limited partial structure and the antigen to which they bind.
10. The Specification discloses a number of CD123 antibodies that are defined by particular amino acid sequences for the heavy and light chain variable regions and CDRs thereof. The specification also discloses 1 antibody (1B7) that is defined by particular amino acid sequences for the heavy and light chain variable regions. This antibody, having a variable light chain having the amino acid sequence SEQ ID NO: 92 (CDR1, CDR2, CDR3 comprising the amino acid sequences of SEQ ID NO: 93, SEQ ID NO: 94 and SEQ ID NO: 95, respectively) and a variable heavy chain having the amino acid sequence SEQ ID NO: 97 (CDR1, CDR3, CDR3 comprising the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99 and SEQ ID NO: 100, respectively), is disclosed as binding to the extracellular domain of CD123 (See Example 3 at pp. 75-80, for example). However, the specification does not provide sufficient written description as to the structural features of the claimed genus of antibodies having variations or deletions with the 6 CDRs from this antibody that have the same binding specificity and functional activity.
11. 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
12. It is well known that minor structural differences even among structurally related compounds can result in substantially different biology, expression and activities. Based on the instant disclosure, one skilled in the art would not know which residues in the CDRs are critical for binding. There is insufficient guidance to direct a person of skill in the art to select or to predict particular residues in the CDRs as essential for binding to the extracellular domain of CD123.
13. It is well established in the art that the amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff, et al. (PNAS, 1982. Vol. 79, page 1979; cited by Applicant). Rudikoff et al. teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum, et al. (J. Mol. Biol., 262:732-745) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left column). De Pascalis, et al. (Journal of Immunology, 2002. 169:3076-3084) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right column). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left column). Wu, et al. (Journal of Molecular Biology, 1999. 294:151-162) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left column) but certain residues have been identified as important for maintaining conformation.
14. In the absence of sufficient direction and guidance, the disclosure of an antibody having a variable light chain having the amino acid sequence SEQ ID NO: 92 (CDR1, CDR2, CDR3 comprising the amino acid sequences of SEQ ID NO: 93, SEQ ID NO: 94 and SEQ ID NO: 95, respectively) and a variable heavy chain having the amino acid sequence SEQ ID NO: 97 (CDR1, CDR3, CDR3 comprising the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99 and SEQ ID NO: 100, respectively) does not provide sufficient written description for the entire genus of antibodies encompassed by the claims, which encompass variations within the CDRs, in view of the evidence cited supra.
15. For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species, cannot be achieved by disclosing only one or two species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
16. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must 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.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structure of the encompassed genus of antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
17. One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
18. Therefore, only an antibody comprising (1) a light chain variable domain having the amino acid sequence SEQ ID NO: 92 and a heavy chain variable domain having the amino acid sequence SEQ ID NO: 97, (2) antibodies comprising the full complement of 6 CDRs from said variable domains in their proper order (i.e., light chain CDR1, CDR2, CDR3 comprising amino acid sequences SEQ ID NO: 93, SEQ ID NO: 94 and SEQ ID NO:L 95, respectively, and heavy chain CDR1, CDR3, CDR3 comprising amino acid sequences SEQ ID NO: 98, SEQ ID NO: 99 and SEQ ID NO: 100, respectively), but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Summary
19. No claim is allowed.
Advisory Information
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/JON M LOCKARD/
Examiner, Art Unit 1647
January 5, 2026