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 .
Status of Claims
Claims 3, 5, 6, 8-16, 18, 19, 21, 22 and 26-30 are currently pending.
Claims 3, 5, 8, 10-12, 14, 15, 16, 18, 21, 22, 26 and 27 are amended.
Claims 28-30 are new.
Claims 3, 5, 6, 8-16, 18, 19, 21, 22 and 26-30 are currently 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. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The U.S. effective filing date of all claims under examination is set at 08/02/2021 based on the CN202110881474.1 application (filed on 08/02/2021).
Information Disclosure Statement
The information disclosure statements (IDS) submitted are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 18 and 19: http://www.gcg.com
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 10, 11 and 12 are objected to because of the following informalities:
Claim 10 recites the term “(Fab’)2” in line 8. It is suggested that the term be amended to “(Fab’)2” wherein the numeral 2 is in subscript format.
Claims 11 and 12 appear to contain typographical errors. It is suggested that the phrase “an antigenic site binding to CD79b” in lines 4 of both claims be amended to “an antigen-binding site binding to CD79b”.
Appropriate correction is required.
Claims 13-15, 27 and 28 are objected to as being dependent on an objected base claim (claim 11).
Claim Rejections - 35 USC § 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.
Claims 10, 19, 22, 26, 29 and 30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites the phrases “a single-chain antibody (e.g., scFv)” and “a camelid antibody (a heavy chain antibody)”. The metes-and-bounds of the claim are unclear because it is unclear how, or if, limitations (i) “a heavy chain antibody” within an open and close parentheses; and (ii) following the term “e.g.”, limit the claims. To obviate this rejection, it is suggested that:
“a single-chain antibody (e.g., scFv)” be amended to “a single-chain antibody (
“a camelid antibody (a heavy chain antibody)” be amended to “a camelid antibody,
Claim 19 recites the term “preferably” twice (line 2 and line 3). The metes-and-bounds of the claims are unclear because it is unclear how, or if, possible limitations following “preferably” limit the claims. Description of preferences should be properly set forth in the specification rather than the claims. If stated in the claims, preferences may lead to confusion over the intended scope of a claim.
Claim 22 recites the phrase "… the immunoconjugate thereof” in lines 2-3. There is insufficient antecedent basis for “the immunoconjugate thereof” in the claim.
Claim 26 recites the phrase "… the pharmaceutical composition comprising the antibody or antigen-binding fragment thereof” in lines 4-5. There is insufficient antecedent basis for “the pharmaceutical composition” in the claim.
Claim 29 recites the phrase "… the immunoconjugate thereof” in line 2. There is insufficient antecedent basis for “the immunoconjugate thereof” in the claim. This rejection can be obviated if the claim were amended to recite “….an immunoconjugate thereof”.
Claim 30 recites the phrase "… the pharmaceutical composition comprising the antibody or antigen-binding fragment thereof” in lines 3-4. There is insufficient antecedent basis for “the pharmaceutical composition” in the claim. This rejection can be obviated if the claim were amended to recite “….a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof”.
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 26 and 30 are 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 for killing CD79b expressing cells in a subject comprising administering a bispecific antibody that binds to CD79b and CD3, does not reasonably provide enablement for a method for preventing and/or treating just any disease or disorder related to either CD79b or CD3 alone. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The nature of the invention
Instant claim 26 is drawn to a method for preventing and/or treating a disease or a disorder related to CD79b and/or CD3, which includes a disorder related to only CD79b, or a disorder related to only CD3, or a disorder related to both CD79b and CD3, comprising administering to a subject an effective amount of the CD79b “monospecific” antibody or the antigen-binding fragment thereof recited in instant claim 3.
Instant claim 30 is drawn to a method for preventing and/or treating a disease or a disorder related to CD79b and/or CD3 in a subject, which includes a disorder related to only CD79b, or a disorder related to only CD3, or a disorder related to both CD79b and CD3, comprising administering to a subject an effective amount of the CD79b/CD3 “bispecific” antibody or the antigen-binding fragment thereof recited in instant claim 13.
The breadth of the claims
Instant claim 26 is broad in that it encompasses prevention and treatment of any disease related to either CD79b or CD3, and any disease related to both CD79b and CD3, using a CD79b monospecific antibody.
Further, instant claim 30 is broad in that it encompasses prevention and treatment of any disease related to either CD79b or CD3, and any disease related to both CD79b and CD3, using a CD79b/CD3 bispecific antibody.
The amount of direction provided by the inventor/the existence of working examples
The specification discloses that humanized monospecific CD79b antibodies were able to bind to CD79b on the surface of Ramos and BJAB cells which are B-cell non-Hodgkin's lymphoma cells lines (Example 7, Pg 28 and FIG. 3 and 4). The specification also discloses that humanized CD79b antibodies can effectively activate NF-AT signaling pathway downstream of ADCC in Jurkat-ADCC NF-AT luciferase effector cells when incubated with 293T-hCD79b target cells and said effector cells (Example 8, Pg 28-29 and FIG. 5). However, the specification does not disclose ADCC effects of CD79b antibodies on any diseased cells.
The specification also discloses the binding kinetics of anti-CD79b/CD3 antibodies for human CD79b, human CD3, and cynomolgus monkey CD3 using surface plasmon resonance (Example 10, Pg 37-38 and Tables 5 and 6). The specification discloses killing of B-cell non-Hodgkin’s lymphoma cell lines by anti-CD79b/CD3 antibodies (Example 13, Pg 39-40 and FIG. 9) and levels of T cell activation and cytokine release during killing of B-cell Non-Hodgkin’s lymphoma cell lines by anti-CD79b/CD3 antibodies (Example 14, Pg 40-42 and FIG. 11). The specification further discloses the anti-tumor efficacy of anti-CD79b/CD3 antibodies in NOG mice inoculated with human B-cell non-Hodgkin's lymphoma cell line that are WSU-DLCl2 and Ramos cells (Example 17, Pg 43-45). Tumor growth curves of FIG. 16 showed that the anti-CD79b/CD3 antibodies 38D9B3.11/sp34.87, 38D9B3.11/sp34.24, and 11G10.9.pl/sp34.24 could significantly inhibit the growth of WSU-DLCL2 cells. Similarly, tumor growth curves of FIG. 17 showed that the anti-CD79b/CD3 antibodies 38D9B3.11/sp34.87, 38D9B3.11/sp34.24, and 11G10.9.pl/sp34.24 could significantly inhibit the growth of Ramos cells.
However, these teachings do not enable the full breadth of the claims because the specification has not shown that:
the monospecific CD79b antibody, i.e. the antibody that lacks CD3 binding functionality, is effective in preventing or treating any disease;
the bispecific CD79b/CD3 antibody is effective in preventing any disease or specifically any disease related to CD79b; and
the bispecific CD79b/CD3 antibody is effective in preventing or treating any disease or specifically any disease related to CD3.
The state of the art/the level of predictability in the art
The state of the art teaches that cancer treatment is highly unpredictable. For example, even though EGFR, a cell surface receptor, was identified in some cancers as a drug target, the in vitro effectiveness of a drug in inhibiting EGFR turned out to be a poor proxy for how effective that drug actually was in treating cancer in vivo during clinical trials. See OSI Pharmaceuticals , LLc, v. Apotex Inc, 939 F.3d 1375, 2019.
Also, the state of the art at the time of filing was such that the functionality of an anti-tumor antibody was dependent on both its action on the intended target and whether or not the modulation of said target had an effect on any particular cancer cell (Baxevanis. Expert Opinion: Drug Discovery, Vol. 3, No. 4, Pg. 441-452, 2008). To illustrate this point, the therapeutic antibody trastuzumab targets the receptor HER-2 (HER-2/neu) which is overexpressed in some breast cancers and so is a viable treatment for said breast cancers (Baxevanis Pg. 444, column 2, lines 19-24). Trastuzumab disrupt HER-2 catalytic activity and since HER-2 activity support growth of cancer cells in which they are overexpressed, inhibition of HER-2 by trastuzumab has been therapeutic when administered to breast cancer patients (Baxevanis Pg. 443, column 1, paragraph 1; Table 1, column 3 and Pg. 444, column 2, lines 19-22). Further, rituximab is an antibody against CD20 antigen which is expressed on most B cells including B-cell lymphomas (Baxevanis Pg. 445, Column 1, Lines 36-38). Rituximab causes tumor cell lysis by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) and so its therapeutic benefit is provided by specifically inducing cancer cell death (Baxevanis Pg. 445, Column 1, Lines 38-39). Therefore, it has been used to treat B-cell lymphomas and relapsed or refractory low-grade non-Hodgkin's lymphoma (a type of B-cell lymphoma) (Baxevanis Pg. 444, Table 1 and Pg. 445, Column 1, lines 41-50).
Further, it is well known in the art that the prevention of any disease including cancer, in general, is highly unpredictable. Reasonable guidance with respect to preventing any disease relies on quantitative analysis from defined populations; some of which have been successfully pre-screened and are predisposed to particular types of disease or disorder such as cancer. This type of data might be derived from widespread genetic analysis, cancer clusters, family histories, or randomized controlled trials. For example, Byers, T. (CA Cancer Journal for Clinicians, Vol. 49, No. 6, Nov/Dec. 1999) teaches that randomized controlled trials are commonly regarded as the definitive study for proving causality (1st col., p.358), and that in controlled trials the random assignment of subjects to the intervention eliminates the problems of dietary recalls and controls the effects of both known and unknown confounding factors. Further, Byers suggests that chemo-preventative trials be designed “long-term” such that testing occurs over many years (2nd col., p. 359). Further, the essential element towards the validation of any preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical cancer. This would require monitoring a large population with the claimed agents and linking such results with subsequent histological confirmation of the presence or absence of disease.
Based on the instant disclosure and prior art, there is no known method through which one of ordinary skill in the art would have been able to reliably predict or otherwise envisage whether:
the monospecific CD79b antibody, i.e. the antibody that lacks CD3 binding functionality, can be effective in preventing or treating any disease or specifically any disease related to CD79b and/or CD3;
the bispecific CD79b/CD3 antibody can be effective in preventing any disease or specifically any disease related to CD79b; and
the bispecific CD79b/CD3 antibody can be effective in preventing or treating any disease and specifically any disease related to CD3.
The Examiner confirms that Applicant is enabled for a method for killing CD79b expressing cells in a subject comprising administering the claimed CD79b/CD3 bispecific antibodies.
Conclusion
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to methods for preventing and/or treating just any disease or just any disorder related to both CD79b and CD3, or related to either CD79b or CD3 in a subject, by administering a CD79b monospecific antibody, or by administering a CD79b/CD3 bispecific antibody, and Applicant is not enabled because it has not been shown that the CD79b monospecific antibody can be used for the said method, or that the CD79b/CD3 bispecific antibody can be used in preventing a disease related to CD79b and/or CD3, or that the CD79b/CD3 bispecific antibody can be used in treating a disease related to CD3.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require an unreasonable amount of experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
Allowable Subject Matter
The following antibody or an antigen-binding fragment thereof that binds to CD79b are free of prior art:
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Conclusion
Claims 3, 5, 6, 8, 9, 16, 18 and 21 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 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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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642
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