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 .
Claims Status
Claim(s) 1-20 is/are currently pending and presented for examination on the merits.
Drawings
The drawings are objected to because:
Figs. 5A-B, 6, 9, 12-15, 22D, and 30A-D are not clearly legible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., CellMosaic Inc., Dynabeads, ThermoFisher Scientific, BioLegend, Invitrogen, Difco Laboratories, ATCC, Jackson Laboratory), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim(s) 3 is objected to because of the following informalities:
Vincristine is repeated (twice) in lines 2-3.
Paclitaxel is repeated (twice) in lines 2-3.
Etoposide is repeated (thrice) in lines 3-4.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 7-8 and 18-19 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 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-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim(s) 7-8, 18-19, are rejected for making reference to tables within the specification and/or figure(s). Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.” See MPEP 2173.05(s).
Claim Rejections - 35 USC § 112(a)
Claim(s) 1-20 is/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.
Claimed Invention
Claim(s) 1-20, are drawn to an anti-CD6 ADC that binds CD6 antigen.
Breadth of Claims
Further the invention as disclosed in claim(s) 1-6, 9-17, 20 recite(s) “…an anti-CD6 antibody, or CD6 binding portion thereof…” in claims 1(a), 14(a), and 20(a)(i). One of ordinary skill in the art would understand that the 6 CDRs of an antibody are responsible for antigen binding characteristics, including antigen recognition and specificity. The claim does not disclose the structure associated with the claimed function. The instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision all of the possible light and heavy chain sequences, particularly in the CDR regions, such that the obtained structure would result in the claimed functions (e.g. CD6 antigen binding).
The invention as disclosed in claim(s) 7-8 and 18-19 are readable to 3 or fewer LCDRs, which is effectively half or less than half of an antibody binding site, as being sufficient for a functional antibody binding region. Specifically, the claim limitations as written require “one or more CDRs from Table 1” (claims 7, 18) or “comprises one or more variable regions shown in…” (claims 8, 19), which is readable to one light chain variable region (VL) sequence comprising 1-3 CDRs (e.g., LCDR1-3, LCDR1-2), which is effectively half ore less than half of an antibody binding site missing the remaining LCDR(s) (e.g., LCDR3) and/or the heavy chain variable (VH) complement (with 3 HCDRs) that would create the full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use half or less than half of an antibody binding domain (e.g., LCDR1-3, or LCDR1-2) and reasonably expect to maintain CD6 antigen binding function.
Further, the invention as disclosed in claim(s) 7-8 and 18-19 are readable to 3 or fewer HCDRs, which is effectively half or less than half of an antibody binding site, as being sufficient for a functional antibody binding region. Specifically, the claim limitations as written require “one or more CDRs from Table 1” (claims 7, 18) or “comprises one or more variable regions shown in…” (claims 8, 19), which is readable to one VH sequence comprising 1-3 CDRs (e.g., HCDR1-3, HCDR1-2), which is effectively half or less than half of an antibody binding site missing the remaining HCDRs (e.g., HCDR3), and/or the VL complement (with 3 LCDRs) to create a full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use half or less than half of an antibody binding domain (e.g., HCDR1-3, or HCDR1-2) and reasonably expect to maintain CD6 antigen binding function.
Scope of Disclosed Species
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The anti-CD6 antibodies in the Applicant disclosure (see Table 1, a summary is provided above for ease of review) with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the anti-CD6 antibodies that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that differences in the 6 CDR sequence(s) is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, US 2017/0362331 A1 (hereinafter “US331”) taught anti-CD6 antibodies were recognized in the art as a promising therapeutic for T cell mediated diseases [e.g., title, abstract]. US331 taught various separate species of anti-CD6 antibodies [e.g., ¶ 0007, 0025-0028, 0059-0062]. Therefore, the prior art demonstrates that the binding of CD6 antigen is possible by various anti-CD6 antibodies. The prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in anti-CD6 antibody that would allow prediction of all of the possible combinations of CDR residues that specifically bind to CD6 antigen.
Thus, the CDR sequence(s) of an antibody sequence that bind a specific antigen are highly unpredictable and one skilled in the art could not a priori make any predications nor envisage the breadth of all of the possible structurally unrelated CDR combinations that would still possess the required function(s) of binding CD6 antigen.
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict all of the possible combinations of CDR residues that would result in an antibody that binds CD6. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 1, 14, and 20 would need to recite (1) the 6 CDR set(s) (e.g., HCDR1-3 and LCDR1-3) in each of the antibody/antibodies that bind CD6 antigen, without variability in the sequences thereof; or (2) the VH and VL pair(s) (e.g., comprising HCDR1-3 and LCDR1-3, respectively) in each of the antibody/antibodies that bind CD6 antigen, without variability in the sequences thereof (e.g., because variability in the VH or VL would constitute variability in the CDRs, which would not meet written description). Dependent claims 2-13 and 15-19 can overcome this rejection by amending claims 1 and 14 as described above. Applicant is further advised that claims 7-8 and 18-19 will no longer be further limiting after amending claims 1 and 14 as described above.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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