DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-5, 8-12, 27-48 are pending and are under examination.
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 1-5, 8-12, 27-48 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.
The scope of the antibodies encompassed in claim 1 is unclear and indefinite. The claim recites a humanized antibody obtained from a mouse antibody, or a mouse antibody, said mouse antibody being selected from a group of particular VH and VL sequences. As an initial matter, it is not clear if “said mouse antibody” modifies both recitations of a mouse antibody in the preamble. For example, do the claims encompass any humanized antibody obtained from any mouse antibody or do the claims only encompass humanized antibody obtained from the mouse antibody having the defined VH/VL regions of the claim. Furthermore, the claim also is indefinite in that it is directed to a mouse antibody, said mouse antibody being selected from the group consisting of “an antibody” comprising a defined VH/VL of certain SEQ ID Nos. This is unclear because the claim recites a mouse antibody (narrow limitation), but then also recites that is selected from “an antibody” (broad recitation). A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For example, would an antibody comprising the VH and VL of SEQ ID NO: 51 and 52 and a human Fc region be within the scope of the claimed mouse antibody or not. On the one hand, it would not be a “mouse antibody”, but on the other hand it is within the scope of “an antibody” comprising VH of SEQ ID NO: 51 and VL of SEQ ID NO: 52. The parenthetical recitation of (2-12B12-F4) is indefinite for the same reasons, i.e. broad limitation of “antibody” and narrow limitation of parenthetical specific antibody. The claim is also indefinite in that it lacks antecedent basis for “the variable region of the heavy chain SEQ ID NO: 51” and “the variable region of the light chain SEQ ID NO: 52”, for example. For the purposes of examination, the claim is being interpreted requiring a. humanized antibody obtained from a mouse antibody having the recited VH/VL SEQ ID Nos or a mouse antibody having the recited VH/VL SEQ ID Nos.
An amendment to recite, for example, a mouse antibody or a humanized antibody obtained from said mouse antibody, said mouse antibody being selected from the group consisting of: a mouse antibody comprising a heavy chain variable region (VH) having the amino acid sequence of SEQ ID N: 51, and a light chain variable region (VL) having the amino acid sequence of SEQI DNO: 52, for example, would clarify the above issues.
However, the claims are indefinite for other reasons that would not be remedied by the above suggestion. For example, the scope of a humanized antibody obtained from a mouse antibody having a VH of SEQ ID NO: 51 and VL of SEQ ID N: 52, is also unclear and indefinite. What portions of the VH/VL are required? Would the CDRS be required? If so what specific residues would constitute the CDRs. Different numbering schemes exist for CDR determination. Although the claim appears to show CDRs in bold, it is not clear if humanized antibody would require said bolded regions or whether other CDR numbering schemes would be encompassed for humanization. The specification does not define the scope of the claim but merely gives examples, such as a humanized antibody that comprises all of the CDRs corresponding to those of a non-human antibody (see page 24). Furthermore, dependent claim 2, recites that the VL region can comprise a first CDR “QNLLYSSNNKNY (SEQ ID NO: 49)”. However, none of the VL regions of claim 1, from which claim 2 depends, have said CDR. Thus, the claims appear to encompass humanized antibodies that include CDR variants, and it is not clear what would be the minimal sequence required for an antibody to be considered a humanized antibody obtained from a mouse antibody with the recited VH and VL sequences.
Claim 3 is indefinite in that it recites a “humanized” antibody that is selected from the group consisting of “an antibody” comprising “the VH region SEQ ID NO: 12” and “the VL region SEQ ID NO: 13” which is indefinite and lacks antecedent basis for the same reasons as set forth above for claim 1. Additionally, the claim recites an antibody (broad recitation) and then in parenthesis (humanized 9-8F2-B11) which narrower. This is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The scope of claim 5 is unclear and indefinite. The claim is directed to a polynucleotide having a nucleic sequence encoding an antibody as defined in claim 1, wherein the nucleotide sequence encoding, for example, SEQ ID NO: 51 is SEQ ID NO: 53. It is not clear if the claimed polynucleotide must comprise SEQ ID NO:53 or not. . Claim 5 does not recite that the polynucleotide has SEQ ID NO: 53, but rather, recites that the nucleic acid sequence encoding SEQ ID NO: 51 is SEQ ID NO: 53. Therefore, it is not clear what portion of SEQ ID NO: 53 (if any) would be required to meet the claim limitations. In other words, the way the claim is worded, the limitation appears to refer to a product by process limitation, i.e. an antibody having a VH encoded by SEQ ID NO: 53, wherein claim 5 would then encompass any nucleotide sequence encoding the antibody. The scope of the claims is unclear and indefinite. Claim 5 also recites multiple “and” statements between the recited SEQ ID Nos., rendering the claim unclear.
Claim 28 and 30 are indefinite for the same reasons set for above for claim 5, i.e. it is unclear whether the claim comprises the nucleotide sequences of the recited SEQ ID Nos. or not.
Regarding claim 9, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 9 is also unclear since it recites that the vector is selected form the group consisting of without an “and” separated the recited species, rendering it unclear what the group actually consists of.
Claim 12 is unclear in the recitation that the one or more antibodies “consist of the following alternative combinations”. Do the claims require all the combinations? One of the combinations? Furthermore, the metes and bounds of, for example, a “humanized antibody 3-12B12-F4” that is obtained from a mouse antibody having VH of SEQ ID NO: 51 and VL of SEQ ID NO; 52 is indefinite for the same reasons set forth above. For example, which residues of the SEQ ID Nos are required? What is the significance on claim scope of “3-12B12-F4”. The scope of the claim is unclear.
Claim 33 is indefinite since it is unclear what “one or more” nucleotide sequences as defined in claim 4 encompasses. Claim 4 is directed to “a polynucleotide having a nucleotide sequence” encoding an antibody as defined in claim 1. Claim 4 only recites “a nucleotide sequence”, and it is unclear what the one or of claim 33 is meant to refer to. One or more of the nucleotide sequence of claim 4, i.e. multiple copies of the same nucleotide sequence. Or are the claims meant to encompass combinations of nucleotide sequence encoding one or more antibodies from claim 1? Claims 34-35 are indefinite for the same reasons.
Regarding claim 35, the claim is also indefinite in the recitation that the composition comprise “one or more together with one or more or one or more nucleotide sequences”, which is unclear and indefinite.
Claim 36 is indefinite for the same reasons set forth above for claims 33-35, i.e. claim 36 recites one or more vectors as defined in claim 8, while claim 8 is drawn to a vector.
The scope of the preamble recited in claims 37-47 is unclear and indefinite. For example, it appears that the word “reducing” could modify both elements of the claimed preamble, i.e. a method for reducing likelihood of or reducing treatment of SARS Co-V. Or does the claim meant to be read as a method for reducing likelihood of or for reducing treatment of SARS-CoV2?
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 is recites a vector having a nucleotide sequence according to claim 4, however, claim 4 is directed to a polynucleotide having a nucleotide sequence, and therefore claim 8 does not require all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-2, 4-5, 8-12, 27-28, 31, 33-34, 36-38, 40-41, 43-46, 48 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The instant claims encompass a genus of humanized antibodies obtained from a mouse antibody, said mouse antibody being selected from the group consisting of an antibody comprising VH and VL of SEQ ID NO; 51 and 52, SEQ ID NO: 1 and 2, SEQ ID NO: 3 and 4, and SEQ ID NO; 5 and 6, respectively. The claims do not require the 6 CDRs from said VH/VL. For example, see dependent claim 2, which recites that the VL region can comprise a first CDR “QNLLYSSNNKNY (SEQ ID NO: 49)”. However, none of the VL regions of claim 1, from which claim 2 depends, have said CDR. Thus, the claims appear to encompass humanized antibodies that include CDR variants. For example, the claims would encompass humanized antibodies derived from each SEQ ID NO pair, wherein they contain numerous different mutations in each CDR as compared to the parent mouse VH/VL. The claims do not require any functionality of the claimed antibodies. In other words, the claims would encompass an extremely large genus of different humanized antibodies that could be derived from, for example, a VH and VL of SEQ ID NO: 51 and 52, including those with mutations that effect antigen binding specificity. Claim 2, even though it recites CDRs, still encompass a genus of antibodies of any specificity since the VH and VL framework sequence can be varied, which as noted below, can be critical to antigen binding. The present claims would encompass a genus of structurally distinct antibody sequences wherein the binding specificity is of an unknown nature.
The state of the art is such that the 6 CDRs of an antibody are critically involved in antigen binding, that even single amino acid changes can alter antigen specificity of binding, and that CDR mutations are unpredictable in terms of affinity, specificity, and solubility, and are also context dependent (see Hall, 1992, and Rabia, 2018). See also Chen which teaches that a single amino acid change in a CDR2 can abolish antigen binding, and that increasing the number of mutations dramatically influences loss of binding (See page 858, in particular). Furthermore, in addition to CDRs, antibody framework sequences in the VH and VL are critical to antigen binding (See Dondelinger, 2018). Thus, the state of the art is such that while a particular VH/VL sequence would define antigen binding specificity, antibodies derived therefrom wherein changes are made in the CDRs or VH/VL framework would alter antigen binding function or antigen binding specificity of any given antibody. Therefore, the present claims would encompass a genus of structurally and functionally distinct antibodies that could bind a genus of different (unknown) antigens. Making and using said antibodies would be highly unpredictable. Claims 37-38, 40-41, 43-46, 48 encompass using the genus of said antibodies having CDR mutations and VH/VL framework mutations, thus having a genus of antigen specificities, to treat or detect SARS-CoV-2 infection, which would also be highly unpredictable.
Thus, based on the breadth of the claims and the unpredictability of the art, the instant specification must provide a sufficient and enabling disclosure, commensurate in scope with the instant claims. The instant specification discloses humanized antibodies having 3 specific VH CDRs and three VL CDRs as defined in claim 2. However, the only discloses use of said antibodies is to bind to a receptor binding domain (RBD) of the spike protein of SARS-CoV-2. This is not commensurate in scope with the instant claims, which encompass a genus of different humanized antibodies, including those with numerous CDR or VH/VL framework mutations, wherein they could be used to bind to any antigen. Thus, based on the breadth of the claims, the unpredictability of the art, and the lack of guidance provided by the instant specification, it would require undue experimentation to make and use the antibodies as broadly claimed.
It is noted that amendment to claim 2 to recite that the humanized antibody binds to a receptor binding domain (RBD) of SARS-CoV-2 spike protein, would overcome the enablement rejection for that claim.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 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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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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