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 1-20 are pending and examined on the merits.
Claim Objections
Claims 5, and 6 are objected to because of the following informalities: the word processing error of “amino acid sequences have at least” rather than “amino acid sequences having at least”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 7, 8, 13 and 14 are 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.
(A)Claims 7 and 8 state that the antibody or antigen-binding fragment thereof of claims 1 and 2 is a monoclonal antibody. Claims 1 and 2 require an antibody which binds to HPV6 L1 protein, said antibody defined by CDR regions in the light and heavy chains. The specification defines “monoclonal” as
“…an antibody obtained from a substantially homogeneous antibody population, i.e., the population comprising a single antibody is identical except for possible mutations (e.g., natural mutations) that may be present in minimal amounts. Thus, the term “monoclonal” indicates the nature of the antibody, i.e., not a mixture of unrelated antibodies. In contrast to polyclonal antibody formulations that typically include different antibodies directed to different determinants (epitopes), each monoclonal antibody of a monoclonal antibody formulation is directed to a separate determinant on the antigen. In addition to their specificity, monoclonal antibody preparations have the advantage that they are generally not contaminated with other antibodies. The term “monoclonal” cannot be understood as requiring the production of the antibody by any particular method. The term monoclonal antibody specifically includes chimeric antibodies, humanized antibody and human antibody.
The requirement for a specific antibody paratope comprising the CDRs of the heavy and/or light chains in claims 1 and 2 exclude polyclonal antibodies. The instant antibodies must be made by recombinant means involving expression of a nucleic acid encoding the light and/or heavy chains of an antibody having the required CDR sequences. As such the antibodies and antigen-binding fragments of claims 1 and 2 are monoclonal. Thus, claims 7 and 8 fail to further limit the subject matter of the claims upon which they depends.
(B)Claims 13 and 14 require that the antibody or antigen-binding fragments of claims 1 and 2, respectively, include Fd fragment, Fd’ fragment, or a single domain antibody. An Fd fragment is a heavy chain portion of a Fab, VH-CH1, obtained by papain digestion of the Fab and has no light chain component. A Fd’ fragment is a heavy chain component of Fab’ derived from pepsin digestion of F(ab’)2 and has no light chain component.
A single domain antibody is known in the art as a camelid VhH, shark V-NAR or mouse Vh domains (Hollinger and Hudson, Nature Biotechnology, 2005, Vol. 23, pp. 1126-1136, see page 1127, line 7 under the heading “Fab, Fv and single-V-type domains” to column 2, line 17). The CDR sequence of SEQ ID NO: 5-7 and SEQ ID NO: 8-10 were raised in a rabbit by immunization with the HPV6 L1 protein. Thus, the CDR sequences of the heavy chain of the claim 1 would not be present in camelid VhH, shark V-NAR or mouse Vh domain. Thus, claims 13 and 14 fail to include all the limitations of claim 1 upon which they depend.
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 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 5 and 6 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.
Claims 5 and 6 are vague and indefinite in the recitation of wherein the light chain constant region is an amino acid sequence of at least 90%, 92%, 95%, 98% or 100% sequence identity to SEQ ID NO: 24 of the light chain constant region of an anti-HPV L1 protein or an amino acid sequence of at least 90%, 92%, 95%, 98% or 100% sequence identity to SEQ ID NO: 26 of the heavy chain constant region of an anti-HPV L1 protein. Claim 1 specifies the light chain variable region in alternative form from the heavy chain variable region. It is unclear if the amino acid sequence of at least 90%, 92%, 95%, 98% or 100% sequence identity to SEQ ID NO: 24 of the light chain variable region pertains to the antibody of claim 1 wherein only the heavy chain CDR sequences are defined. It is unclear if the amino acid sequence of at least 90%, 92%, 95%, 98% or 100% sequence identity to SEQ ID NO: 16 of the heavy chain variable region pertains to the antibody of claim 1 wherein only the light chain CDR sequences are defined. It is noted that claims 3 and 4 on which claims 5 and 6 depend, fail to specify that the light chain constant region is attached to the light chain variable region of claim 1, and that the heavy chain constant region is attached to the heavy chain variable region of claim 1, thus failing to establish the presence of both the light chain variable region and the heavy chain variable region of claim 1 are part of the antibodies of claims 3 and 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.
Claims 13, 14 and 18-20 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 factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
(A)Claim 18 is drawn to a method for detecting the presence of HPV6L1 protein in a sample comprising a) coating the antibody or antigen-binding fragment thereof of claim 1 onto an assay surface; b) contacting the coated assay surface with the sample to be tested for a length of time to allow binding of the L1 protein in the sample , and then washing the assay surface; and c) contacting the assay surface with the antibody of claim 1 or antigen binding fragment thereof conjugated to a reporter group for a length of time sufficient to allow binding of the conjugated antibody and then washing the assay surface; and d) detecting the signal of the reporter group.
Claim 1 is drawn in part to the anti-HPV6 L1 antibody or an antigen-binding fragment thereof having a light chain variable region comprising the CDR sequences of SEQ ID NO: 5-7, and a heavy chain variable region comprising the CDR sequences of SEQ ID NO: 8-10. Thus, the paratope of the anti-HPV6 L1 antibody is defined by both the light chain CDRS of SEQ ID NO: 5-7 and the heavy chain CDRs of SEQ ID NO: 8-10.
Claim 19 specifies that the antibodies of claim 1 in steps “(a)” and “(c)” are the same or different.
Both of steps a) and c) require the antibody or antigen binding fragment thereof of claim 1. Said antibody binds to the L1 protein of HPV6 and has a paratope defined by the heavy chain CDRs of SEQ ID NO: 8, 9 and 10 and the light chain CDRs of SEQ ID NO: 5, 6 and 7. The antibody paratope controls the epitope of L1 to which the antibody will bind. Thus, both antibodies of part (a) and (c) of claim 18 will bind to the same epitope of L1. Part b) of claim 18 will result in binding of any HPV6 L1 protein in the sample to the immobilized antibody coated on the assay surface through the formation of a complex of the specific epitope of the L1 protein and the antibody paratope of claim 1. Part (c) will not result in the formation of a complex between the bound L1 protein and the conjugated antibody of claim 1 because the epitope recognized by the conjugated antibody of claim 1 will be blocked by the antibody used to capture the L1 protein in step (b). It is noted that the specification provides no objective evidence, nor any art of record, to indicate that the epitope of L1 bound by the R0003 antibody is a repeated epitope such that one molecule of L1 can be bound by more than one R003 antibody. Thus, claims 18-20 will not function as claimed and one of skill in the art would be subject to undue experimentation without reasonable expectation of success in order to practice the claimed method.
(B)Claim 13 and 14 require, in part, that the antibody fragment that binds to the HPV6-L1 protein is an Fd fragment or a Fd’ fragment. A Fd fragment is a heavy chain portion of a Fab, VH-CH1, obtained by papain digestion of the Fab and has no light chain component. A Fd’ fragment is a heavy chain component of Fab’ derived from pepsin digestion of F(ab’)2 and has no light chain component. Neither the specification nor any art of record provides objective evidence that Fd or Fd’ fragments can specifically bind to HPV6 L1 protein in the absence of any light chain variable region. Given the lack of teachings and guidance in the specification, one of skill in the art would be subject to undue experimentation without reasonable expectation of success in order to use the Fd or Fd’ fragments to specifically bind to HPV6 L1 protein.
Claims 1-20 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.
When given the broadest reasonable interpretation, claim 1 encompasses a genus of anti-HPV6 L1 protein antibodies that are defined only by the ability to bind to HPV6 L1 protein and the presence of a light chain comprising .the CDR sequences of SEQ ID NO: 5-7, or the presence of a heavy chain comprising SEQ ID NO: 8-10.
Section 2163 of the M.P.E.P. states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
In the instant case, the genus of antibodies encompasses anti-HPV6 L1 protein antibodies that have structurally undefined heavy chains paired with a structurally defined light chain, and structurally undefined light chains paired with structurally defined heavy chains. The antibody paratope is responsible for the recognition of an epitope. The antibody paratope is made up of the CDRs from both the light and heavy chains. The specification teaches a correlation between the R003 antibody comprising both of the light and heavy chains of claim 1 and the selective binding of the HPV6 L1 protein (paragraphs [0025] and [0071]). The specification fails to provide a written description of any anti-HPV6 L1 protein antibody having only a variable heavy chain from the R003 antibody paired with an undefined light chain, or having only a variable light chain from the R003 antibody paired with an undefined heavy chain. The instant claims do not rely upon the specific CDRs from R003 forming the antibody paratope and the specific binding to HPV6 L1 protein because the claims require only the CDRs from one chain or the another which in isolation do not make up the antibody paratope as in R003.
Claims 3 and 4 are included in this rejection because claims 3 and 4 fail to specify that the light chain constant region is attached to the light chain variable region of claim 1, and that the heavy chain constant region is attached to the heavy chain variable region of claim 1, thus failing to insure the presence of both the light chain variable region and the heavy chain variable region of claim 1 are part of the antibodies of claims 3 and 4.
One of skill in the art could not envisage the structures of members of the anti-HPV6 L1 antibody genus outside of the antibodies possessing the required CDRs from both the light and heavy chains of claim 1
Claim 2 requires that the anti-HPV6L1 protein comprises a light chain variable region having at least 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 20, or a heavy chain variable region having at least 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 12. Claims 5 and 6 require a light chain variable region of an anti-HPV6 L1 antibody which is an amino acid sequence of at least 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 24; or a heavy chain variable region of an anti-HPV6 L1 antibody which is an amino acid sequence of at least 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 26. The specification fails to provide any anti-HPV6 L1 antibodies that have 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 24 or anti-HPV6 L1 antibodies that have 90%, 92%, 95%, or 98% sequence identity to SEQ ID NO: 26. Without the requirement for retaining the CDR regions from both the heavy chain variable region and light chain variable regions in the claims upon which the instant claims depend, the antibody variants above can be substituted at any position within SEQ ID NO: 20, 12, 24, 26. One of skill in the art cannot envisage the members of the genus of claims 2, 5 and 6 as one could do with a well-described genus.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
Prosecution Insights