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
The amendments filed on 9/16/2025 which claims 1, 10, 12 were amended is acknowledged. Claims 4, 7, and 11 were canceled.
Claims 1-3, 5-6, 8-10, 12, and 30-35 are pending in the instant application.
Priority
This application is a 371 of PCT/US2021/025909, filed on 4/6/2021 which claims priority to the provisional application 63140355 filed on 1/22/2021; 63091517 filed on 10/14/2020; 63036016 filed on 6/8/2020; 63018637 filed on 5/1/2020; and 63005788 filed on 4/6/2020.
Withdrawn Objections
The objection to the specification has been withdrawn; applicant removed the references to colors in the drawings where no color drawings were submitted.
The objection to claim 12 is withdrawn, applicant added bullet points to better differentiate the sets of CDRs.
Claim Rejections – 35 USC § 112(a) – Written Description
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, 5-6, 8-10, and 30-35 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.
All except 12
Claims 1-3, 5-6, and 8-9 are drawn to antibodies comprising CDRs with variable residues. The art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody (Kussie 1994 and Chen 1995). Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions. Claim 1 is substantially generic, wherein only 60% of the CDRs need to be preserved, which is further broadened by the generation of any combination of HCDRs and LCDRs pairings between the sets. Claims 2 and 3 merely exclude antibodies comprising 100% sequence identity to the HCDR3 set and the LCDR3 set. Claims 5 and 6 merely exclude antibodies comprising 100% sequence identity to the HCDR1 set and the LCDR1 set. Claims 8 and 9 merely exclude antibodies comprising 100% sequence identity to the HCDR2 set and the LCDR2 set. Thus applicant has failed to meet the written description of antibodies that have only 60% similarity to the CDRs selected from:
HCDR1 set of SEQ ID NO: 73-90;
HCDR2 set of SEQ ID NO: 91-108;
HCDR3 set of SEQ ID NO: 109-126;
LCDR1 set of SEQ ID NO: 127-144;
LCDR2 set of SEQ ID NO: 145-162; and
LCDR3 set of SEQ ID NO: 163-180, wherein the desired binding properties are preserved.
Dependent claims 30-35 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 10-11
Claims 10 is drawn to antibodies comprising mixed and matched VH and VL units. As described in the previous 112(a) rejection above, the art recognizes that a complete set of six CDRs comprise the binding region of antibody (Sela-Culang 2013), and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody (Kussie 1994 and Chen 1995). Due to this unpredictability, applicant does not meet the written description requirement via describing a representative number of species, thus they must provide the core structure responsible for preserving the binding activity. In the instant case, applicant has not provided any examples of mixed and matched VH and VL sets wherein the binding is preserved, nor has applicant provided the core structure responsible for binding (e.g. which complete set of six CDRs is required for binding). Thus applicant has failed to meet the written description of antibodies that have the desired binding properties that comprise mixed and matched HCDRs and LCDRs. See “Allowable Subject Matter” section for how to specify variation in the VH and VL regions.
Claim Rejections – 35 USC § 112(a) – Enablement
Claims 34-35 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 treating covid using antibodies comprising a full set of 6 CDRs in claim 12, it does not reasonably provide enablement for treating covid wherein the CDRs comprise variable amino acid residues. 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.
claim 34-35
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention/Breadth of Claims:
Antibodies that comprise only 60% of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, selected from SEQ ID NOs: 73-90, SEQ ID NOs: 91-108; SEQ ID NOs: 109-126; SEQ ID NOs: 127-144; SEQ ID NOs: 145-162; and SEQ ID NO: 163-180, respectively. Note that any of the CDRs described above can be mixed and matched.
State of the prior art/Predictability or unpredictability of the art:
As described previously in the 112(a) written description rejection: The art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody (Kussie 1994 and Chen 1995). Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions. This is also true of mixing and matching CDRs within a group of antibodies that bind to the same epitope. The binding region of an antibody is highly specific.
Amount of guidance/Existence of working examples:
Applicant has failed to provide any examples that comprise 60% sequence variants of the CDRs described in claim 1 that are effective in binding covid. Applicant has not provided any experimental evidence showing that these CDRS can be mixed and matched without altering the binding properties, necessary for treating Covid.
Quantity of experimentation:
Given the unpredictability of antibody binding upon single amino acid changes to the CDR regions and absent the evidence from Applicant showing that the CDR regions can be mixed and matched without affecting binding to Covid, one of skill in the art, in undertaking the experimentation necessary to determine which of the claimed therapies would be effective, would have no reasonable expectation that the majority of sequence variants would bind covid and/or be successful in treating covid.
Lack of a working example is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP § 2164.
See the decision in Rasmusson v. SmithKline 413 F.3d 1318, 1325 (Fed. Cir. 2005) which stated: “Thus, at the end of the day, the specification, even read in the light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient. [Citation omitted.] ‘If mere plausibility were the test for enablement under §112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the “inventor” would be rewarded the spoils instead of the party who demonstrated that the method actually worked.’”
Therefore, in view of the Wands factors as discussed above, e.g., the amount of guidance provided, the predictability of the art and the lack of working examples, to practice the full scope of the claimed invention herein, a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Allowable Subject Matter
Claim 12 is objected to for being dependent upon a rejected base claim; but would be allowable if rewritten in independent form, including all of the limitations of the base claim and any intervening claims.
Claim 12
Claim 12 is drawn to anti-coronavirus antibodies comprising a specific set of six CDRs. These specific sets CDRs were not found in the prior art. The VH and VL domains described in claims 10 and 11, respectively, containing the CDRs of claim 12 were also not found in the prior art. No references were found that met the limitations of claim 1.
The closest prior art to the VH is that of the anti-CD3 antibody VH taught by Apgar (US20190382486, SEQ ID NO: 42), shown below with the CDR regions underlined. Notably, Apgar fails to teach HCDR3 as comprising at least 60% sequence homology to instant SEQ ID NO: 122 as required by claim 1. Hence no 103 rejection was made.
instant_50 GVQLVESGGGLVQPGGSLRLSCSASGFTFSSYAMHWVRQAPGKGLEYVSGINVNGYDTYY 60
Apgar_42 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVSAISGGGRSTYY 60
***:*****************:***********:***********:**.*. .* .***
instant_50 ADSVKGRFTISRDNSKNTLFLQMISLTAEDTALYYCVKEDTP------LVFDSWGQGTLV 114
Apgar_42 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSPSDVGWGYGFDIWGQGTLV 120
*******************:*** ** *****:***.:: :* ** *******
instant_50 TVSS 118
Apgar_42 TVSS 124
****
The closest prior art to the VL is that of the anti-CD3 antibody VL taught by Lippincott (US20190292258, SEQ ID NO: 92), shown below with the CDR regions underlined.
instant_68 DIQMTQSPSTLSASVGDRVTITCRASQFINSWLAWYQQKPGKAPKLLIYAASSLQSGVPS 60
Lippincott_92 DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASSLESGVPS 60
*************************** *.******************* ****:*****
instant_68 RFSGSGSGTEFTLTINSLQPDDFATYYCQQYDSYSTFGQGTKVEIK 106
Lippincott_92 RFSGSGSGTEFTLTISSLQPDDFATYYCQQYNSYSTFGQGTKVEIK 106
***************.***************:**************
It is understood in the art that changes to CDRs are unpredictable, thus there was no guidance to arrive at the specific CDR’s recited, given the art of record.
Examiner recommends canceling claims 1-3, 5-6, and 8-9 that are drawn to variable CDRs with unknown binding functions.
Examiner recommends canceling claim 10 and splitting it into two dependent claims that are dependent on claim 12, such that one of the new dependent claims is drawn to comprising 60% sequence identity to the VH sequences of SEQ ID NOs: 37-54, and the other new dependent claim is drawn to comprising 60% sequence identity to the VL sequences of SEQ ID NO: 55-72.
Response to Arguments
Applicant’s arguments filed on 9/16/2025 have been fully considered but they are not persuasive.
112(a) Written Description; pg 11, para 1
Applicant argues they have met the written description by describing partial sequence information for all six CDRs in claim 1 and by combining the selection of VH and VL units into claim 10.
The amendments to claim 1 fail to satisfy the written description requirement because they are still drawn to variations in the CDR region, wherein said variants are highly unpredictable. This is also true for claim 10, wherein applicant’s amendments are drawn to mixing and matching sets of VH and VL units, wherein these combinations of VH and VL units were not verified for their binding properties. Because in the case of antibody variable regions, applicant cannot describe the invention using a representative number of species, applicant must then instead specific the core structure required to preserve the function of the antibody binding Covid.
112(a) Enablement; pg 11, para 3
Applicant argues that their amendments describing sequence identifiers into claim 1 have overcome the enablement rejection.
Applicant’s amendments have improved the status of the claims in regards to enablement, but because claim 1 is still drawn to variations in the CDR regions of the antibodies, one of skill in the art would have to carry out undue experimentation in order to determine which of the claimed variants bound covid and which do not. Applicant has described several working sets of CDRs in claim 12, but has not described what variants of the CDRs in claim 1 have the desired function. One of skill in the art cannot a priori predict which of the claimed antibodies would have the desired function of treating Covid, thus applicant has failed to satisfy the scope of enablement requirement.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675