DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Applicant’s amendment filed on August 29, 2024 is acknowledged.
Claims 1-23 have been canceled.
Claims 24-42 have been added.
Claims 24-42 are pending and currently under consideration.
3. Claim 33 is objected to for following informalities:
Claim 33 recites “(Cancelled)” at the end of the claim and without period at the end of the claim. This appears to be an inadvertent error. Appropriate correction is required.
4. 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.
5. Claims 24, 25, 27, 29, 30, 32, 35, and 36 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.
Independent claims 24 and dependent claims thereof are drawn to an anti-CD19 antibody comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the CDRs comprises the amino acid sequence of SEQ ID NOs: 22, 116, 121, 28, 125, and/or 32, respectively.
The claims do not set forth the amino acid sequences for all six CDRs in view of the recitation of “and/or”.
Independent claim 32 is drawn to a humanized monoclonal anti-CD19 antibody comprising a VH that is at least 95% identical to SEQ ID NO:106 and a VL that is at least 95% identical to SEQ ID NO:111.
The specification discloses antibody VH and VL having the amino acid sequences of SEQ ID NO:106 and SEQ ID NO:111, respectively.
The specification adequately described the anti-CD19 antibody comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the CDRs comprises the amino acid sequence of SEQ ID NOs: 22, 116, 121, 28, 125, and 32, respectively, or VH of SEQ ID NO:106 and VL of SEQ ID NO:111.
However, the claims recite a genus of anti-CD19 antibody comprising six CDRs but only not defining the structure of all six CDRs, or a genus of humanized anti-CD19 antibody comprising VH and VL that are at least 95% identical to SEQ ID NOs:106 and 111 as part of the invention without providing a physical structure or testable functional activity for the variants.
The specification has not disclosed which of the amino acids in SEQ ID NOs: 106 and 111 can be changed to maintain the function of CD19 binding or does the specification discloses an anti-CD19 antibody with less than six defined CDRs.
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 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.
For example, Chiu et al. (Antibodies 2019, 8,55; 1-80) teach that of all of the six CDRs, the VH CDR3 most often has changes in conformation with unbound and bound structures are compared. In addition, differences in the orientation of VL with respect to VH are often seen and the induced-fit mode of binding introduces plasticity into the antigen-binding site, expanding antibody diversity beyond that resulting from amino acid residue changes (e.g. see page 5). Further, Chiu et al. teach that studies conducted with multiple institutes in predicting CDRs structure do not appear to yield reliable results (e.g. see 1.2.6. Antibody Modeling in page 6).
Sela-Culang et al. (Frontiers in Immunology, 2013, Vol. 4, Article 302, pages 1-13) shows that each CDR has its own unique amino acid composition different from the composition of other CDRs (e.g. see right col. in page 5). In addition, Sela-Culang et al. teach that each CDR has a unique set of contact preferences, therefore, favoring certain amino acids over others (see lines spanning pages 5-6). Sela-Culang et al. also teach that many attempts to isolate and design individual antigen-binding CDR or CDR derived peptides have failed and it is possible that a CDR on its own may not fold to the same conformation as in the context of the entire Fab crucial for antigen binding (e.g. see first full paragraph in the left col. in page 7).
Thus it is unpredictable as to what amino acids can be changed in the original intact antibodies disclosed in the specification wherein the antibodies would still function by CD19 binning.
It does not appear based upon the limited disclosure of humanized anti-CD19 antibody having specific VH and VL amino acid sequences or six CDR sequences alone that Applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the limited number of species disclosed and the extensive variation permitted within the genus of the humanized anti-CD19 antibody.
“Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997).
The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406.
In the absence of disclosure of relevant, identifying characteristics of the humanized anti-CD19 antibody, there is insufficient written disclosure under 35 U.S.C. 112, first paragraph.
6. Claims 37-39 and 41 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating an autoimmune disease or a B cell lymphoma by administering an anti-CD19 antibody comprising HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NOs: 22, 116, 121, 28, 125, and 32, respectively, does not reasonably provide enablement for more. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir.1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of the skilled in the art to practice the claimed invention.
The scope of the claims encompasses a method of treating a disease or disorder in a human including cancer by administering the anti-CD19 antibody as recited.
The specification discloses that the anti-CD19 antibody can kill human lymphoma cells such as Daudi target cells in vitro and in vivo (e.g. see [00714]) and [00726]).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The specification does not provide a sufficient enabling description of the claimed invention. The disclosure appears to show that the anti-CD19 antibody can kill human lymphoma cells in vitro and in vivo. For example, the specification discloses that the anti-CD19 antibody mediate ADCC against B cell lymphomas such as Daudi cells (e.g. see [00714]).
Further, the specification discloses that the anti-CD19 antibody also mediates depletion of B cells in vivo (e.g. see [00727]) which may correlate to use in human to treat B cell malignancies and autoimmune disease.
The instant claims encompass in their breadth any a method of treating any disease or disorder in a human including any cancer.
However, there does not appear to be sufficient guidance in the specification as field for the claimed method.
It is known that CD19 function is poorly characterized. For example, Schurmans et al. (Advances in Biological Regulation 2026 99;101116:1-6) teach that while CD19 is a validated therapeutic target for B cell malignancy and some autoimmune diseases, CD19 function is still poorly characterized and better understanding could help to mitigate pathologies associated with B cell alteration (e.g. see page 4).
In view of the lack of predictability of the art to which the invention pertains, the lack working examples, the stateof the art teachings, undue experimentation would be required to practice the claimed method of treating a disease or disorder in a human including any cancer by administering the recited anti-CD19 antibody.
7. 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.
8. The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
9. Claim 32 is rejected under pre-AIA 35 U.S.C. 102(e) as being anticipated by Tedder et al. (US 2006/0233791).
Claim 32 is drawn to a humanized monoclonal anti-CD19 antibody comprising a VH that is at least 95% identical to SEQ ID NO:106 and VL that is at least 95% identical to SEQ ID NO:111.
The specification discloses that that one embodiment is an anti-CD19 antibody comprises the CDRs from antibody clone HB12B deposited in ATCC as PTA-6581 (e.g. see [0014] of PGPUB US 2021/0061906). The specification further discloses that the VH of HB12B is SEQ ID NO:34 and VL is SEQ ID NO:52 (e.g. see [0019]).
The instant SEQ ID NO:106 is 97.8% identical to the VH of HB12B of SEQ ID NO:34 and the instant SEQ ID NO:111 is 96.9% identical to the VL of HB12B of SEQ ID NO:52 (see sequence alignments below).
Instant SEQ ID NO:106 alignment to SEQ ID NO:34 of the prior art VH of HB12B:
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322
644
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Greyscale
Instant SEQ ID NO:111 alignment to SEQ ID NO:52 of the prior art VL of HB12B:
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292
610
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Greyscale
Tedder et al. teach monoclonal anti-CD19 antibody HB12B and teach a humanized anti-CD19 antibody comprising VH and VL that are about 95% identical to the VH and VL from HB12B (e.g. see [0090]).
Therefore, the reference teachings anticipate the instant claim.
10. 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.
11. Claims 24-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-9 of US 8,323,653 (drawn to an isolated purified chimeric, humanized, or human mAb comprises VH of SEQ ID NO:106 and VL of SEQ ID NO:111;
Claims 1-9 of US 8,883,992 (drawn to a nucleic acid encoding an anti-CD19 antibody VH of SEQ ID NO:106 and VL of SEQ ID NO:111, an expression vector, a host cell, and a method of producing the antibody); and
Claims 1-8, of US 9,896,505 (drawn to a method of treating a B cell disease by administering a humanized, chimeric, or human anti-CD19 antibody comprising VH of SEQ ID NO:106 and VL of SEQ ID NO:111).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the claims in the US Patents listed above encompass a humanized anti-CD19 antibody comprising the same VH of SEQ ID NO:106 and the same VL of SEQ ID NO:111. As such the claims in the US Patents would anticipate the instant invention. The rejections are necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008) and Amgen, Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
12. The anti-CD19 antibody comprising VH CDRs 1-3 of SEQ ID NOs: 22-116-121 and VL CDRs of SEQ ID Nos: 28-125-32 and an anti-CD19 antibody comprising VH of SEQ ID NO:106 and VL of SEQ ID NO:111 are free of the prior art.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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