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 .
Applicants are informed that examination of the instant application will be conducted by Examiner Blumel, see contact information below.
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 5/18/2026 is acknowledged. Upon further consideration, the Lack of Unity between Inventive Group I and Group II has been withdrawn. Claims 1-15 and 18-20 are examined no the merits.
Applicants elected an antibody comprising the light chain CDRs of SEQ ID NO:s 3, 4 and 6 and the heavy chain CDRs of SEQ ID NO:s 10, 12 and 13. The elected Variable Light chain is SEQ ID NO: 14 and the Variable heavy chain is SEQ ID NO: 16. SEQ ID NO:s 12 and 15 are part of a different antibody and are not examined currently. SEQ ID NO:s 5, 7, 8 and 9 will be examined since they include the elected CDRs.
Claims 18 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/18/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/18/2024 and 3/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See pages 2 and 30 possess hyperlinks.
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below. The specification is objected to because pages 20, 30 and 31 do not contain a specific SEQ ID NO: for each amino acid sequence presented. In addition, the figure description for Drawing 1 does not contain a SEQ ID NO: for the presented amino acid sequences. Applicants are reminded that an amino acid sequence of at least 4 residues in length requires a specific SEQ ID NO:.
Applicants must comply with sequence rules in order to be considered a complete response to this Office Action.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 13 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). The claims are drawn to host cells, which include human organisms. If claim 13 is amended to recite “An isolated host cell…”, this rejection can be overcome.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 7, 14, 15 and 18-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013) (hereafter “Myriad”).
Based upon an analysis with respect to the claims as a whole, claim(s) 1, 7, 14, 15 and 18-20 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more (these claims are interpreted in light of the most recent Guidelines (See “https://www.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter-eligibility)).
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes and the Steps cited below (See flowchart at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf), the claims are directed to an ineligible product/process as further detailed below.
In this case, claim(s) 1, 7, 14, 15 and 18-20 recite or are directed to a composition of matter (Step 1) and recite natural phenomenon(s) (in this case, an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19.) that are directed to a judicial exception (in this case, a natural phenomenon)(Step 2A). Claims 1, 7, 14, 15 and 18-20 do not recite any structure of the claimed antibody, but rather what the antibody can bind to or how it can be used.
Thus the claimed product is not markedly different from its naturally occurring counterpart (see Part I.A.3 of the Interim Eligibility Guidance; Example 2, p. 29). Thus the claims also read upon a pharmaceutical composition (claims 14 and 15) or a composition that is part of a kit (claims 18-20), but these claims do not additionally require anything more than just the antibody. The claimed invention is a composition of matter as recited in Step 1 and a natural phenomenon as recited in Step 2A.
The claims thus recite a nature-based product limitation that does not exhibit markedly different characteristics from its naturally occurring counterpart, or is directed to a “product of nature” exception.
In addition, Budkowska et al. (infra) teach the collection of sera from humans infected with HBV. The sera was analyzed for antibodies specific for PreS1. [see page 27 and right column of page 28] This sera is a mixture of monoclonal antibodies (i.e., a polyclonal solution) and some of the samples from the infected humans contained antibodies specific for PreS1 and PreS2. [see Table 1 and first 2 paragraphs of Results section] Therefore, the sera that contains these antibodies includes an antibody that would inherently be specific for the preS1 antigen at a position corresponding to positions 22, 23, and 25 based on SEQ ID NO: 19 and capable of binding a HBV of genotype A, B, C, D, E, F, G or H. Budkowska et al. establish that the antibody of the present claims include antibodies that are naturally occurring in a human infected with HBV.
Further, in view of Step 2B and the “No” pathway, the claims do not recite additional elements that amount to significantly more than the judicial exception. While the claimed invention also requires a pharmaceutically acceptable excipient to be added with the antibody or a kit comprising a container and the antibody, but not requiring that the container house the antibody, these additional limitations do not amount to significantly more than the judicial exception since the carrier does not provide any additional elements to change a property or function of the antibody.
As pursuant to the Office’s interpretation of the Myriad decision, a recitation of a naturally-occurring product that does not have a substantial or marked difference from the natural product is not patent eligible subject matter. Therefore, claims 1, 7, 14, 15 and 18-20 as written, read upon an antibody that was found to have occurred naturally in nature without being subject to the "hand-of-person" and resulting in a substantial or markedly different product from that found in nature. Therefore, claim(s) 1, 7, 14, 15 and 18-20 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter. This rejection is necessitated by expanded 35 USC §101 USPTO training in view of the USPTO’s interpretation of Myriad. Applicant is directed towards the USPTO memos, which support the analysis of the claims (https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf); please review the latest materials regarding 35 USC §101 rejections. It is suggested that applicant cancel the rejected claims, draw the rejected claims to read upon a non-naturally occurring antibody, recite specific steps that are non-routine/non-conventional, and/or recite products/processes which are substantially or markedly different from the judicial exceptions. Applicant is cautioned to amend the claims according to these suggestions utilizing limitations for which the application would have support.
Claim Rejections - 35 USC § 112(a); First Paragraph
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 1-15 and 18-20 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 monoclonal antibody that comprises the variable heavy chain of SEQ ID NO: 2 and the CDRs of SEQ ID NO:s 10, 12 and 13 and the variable light chain of SEQ ID NO: 1 and the CDRs of SEQ ID NO: 3, 4, and 6, wherein the monoclonal antibody binds to a hepatitis B virus preS1 protein and that such an antibody can inhibit HBV infections, does not reasonably provide enablement for an antibody without an identified 6 CDRs found in the variable light and heavy chains or an antibody that has amino acid variations in the CDRs located in specific variable chains and is also capable of binding to a hepatitis B virus preS1 protein and preventing or treating HBV or detecting HBV. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The claimed invention is drawn to an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19. Wherein the antibody specifically binds to one or more genotypes selected from HBV genotype A, B, C, D, E, F, G or H.
the antibody has tyrosine at position 8 in an LCDR3 sequence of SEQ ID NO: 5 and leucine at position 6 in an HCDR3 sequence of SEQ ID NO: 9 as paratopes;
or
the antibody has amino acid at position 1 in an HCDR2 sequence represented by SEQ ID NO: 8 as a paratope and the amino acid residue at position 1 in the HCDR2 sequence represented by SEQ ID NO: 8 is alanine or serine;
or
The antibody comprises: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5, which includes the more specific CDR of SEQ ID NO: 6; and
(b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, which includes the more specific CDR of SEQ ID NO:10, a heavy chain CDR2 of SEQ ID NO: 8, which includes the more specific CDR of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 9, which includes the more specific CDR of SEQ ID NO: 13;
or
the antibody consists of the light chain variable region of SEQ ID NO: 1 (which possess amino acid variations);
or
the antibody consists of the heavy chain variable region of SEQ ID NO: 21 (which possess amino acid variations);
or
the antibody comprises a light chain variable region represented by SEQ ID NO: 14 and a heavy chain variable region represented by SEQ ID NO: 16.
However, no claim specifically identifies the antibody possessing just the sequences associated with antibody AbS0, such as a claim requiring the variable regions of SEQ ID NO:s 14 and 16.
The claimed invention also requires a polynucleotide encoding the antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19, and an expression vector comprising the polynucleotide and a host cell comprising the expression vector. The antibody can also be part of a pharmaceutical composition for prevention or treatment of HBV infection, or a composition for detecting/diagnosis of HBV, or a kit for detection of HBV.
Applicants have tested the ability of antibody AbS0 to bind to and inhibit HBV from infecting cells in vitro. [see Example 4] However, applicants have not testing this antibody for treating or preventing HBV. Furthermore, since the claimed invention of claims 14 and 15 are using an antibody defined by only what it can bind (the preS1 antigen as positions 22, 23 and 25 corresponding to SEQ ID NO: 19 of a HBV), one of ordinary skill in the art would be exposed to undue experimentation to determine if such an undefined antibody can treat or prevent HBV. This is also true for the ability of such an antibody to be able to detect HBV (claims 18-20).
Thus, the claim is are directed to a broad class of antibodies, only defined by its function and amino acid sequences that might be required or might be fragments thereof or variants thereof. However, relative to the claimed openness to fragments of the CDRs, the specification does not give one of ordinary skilled in the art enough information to choose candidate antigen binding structures from the vast number of options that fall within the fragments of the claimed CDRs, and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. This decision reaffirmed the prior decision made by the Federal District Court in Amgen Inc. v. Sanofi, Aventisub LLC., 987 F.3d 1080 (Fed. Cir. 2021).
The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality … running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, the Supreme Court found that Amgen failed to enable all that it claimed, even if allowing for a reasonable degree of experimentation. Id. at 613; see also Baxalta Inc. v Genentech, Inc., 81 F.4th 1362, 1367, 2023 USPQ2d 1103 (Fed. Cir. 2023) ("[t]he facts of this case are more analogous to—and are, in fact, indistinguishable from—those in Amgen. We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."). Moreover, "[w]e see no meaningful difference between Wands' ‘undue experimentation’ and Amgen's ‘[un]reasonable experimentation’ standards. Id. at footnote 4. See also Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024), which explains that regardless of the technology the Wands factors should be used when assessing enablement.
However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613.
In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
This case is akin to the issue in Amgen Inc. v. Sanofi, Aventisub LLC, in which the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Sanofi-Aventisub at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a ‘vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure.
The instant claims are directed to a class of antibodies that include “a ‘vast’ number of antibodies comprising an undefined structure (claims 1, 7, 11-15 and 18-20), an antibody having one or 3 defined CDRs (claims 2-4 and 8 and 9) or variants of CDRs (claims 5 and 6) and still be able to bind the claimed preS1 epitope and treat, prevent, diagnose and detect HBV, in view of teachings for the specification. It would be necessary to first generate and then screen each candidate antibody and fragments thereof, with the recited function to determine whether it met the functional limitations of “able to binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19”. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
With regard to the antibody AbS0, the instant specification does not disclose any common structural feature delineating which of the claimed variants of AbS0 will have the function of “able to binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19”, or how to distinguish structures with this function from structures without.
The instant claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the antigen binding CDRs they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
The Supreme Court’s 2023 decision in Amgen v. Sanofi, which mainly involves the enablement requirement, states that “where a patentee purports to invent an entire genus, it must enable the entire genus”; “disclosing how to produce some antibodies that perform a specified function is not equivalent to disclosing how to produce all such antibodies – and it is the latter that petitioners claim as their invention”; S. Ct.
The specification does not reasonably provide enablement to make the invention of claims 1-15 and 18-20 as it is currently written. The specification does reasonably provide enablement to make and use the invention of antibody AbS0 as discussed above.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary, the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
In addition, any CDR mutation, which can happen when you recombine all these CDRs into different species is not predictable. This is evidenced by the fact that even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff (Proc Natl Acad Sci USA 1982 Vol 79 page 1979). Rudikoff teaches that the alteration of a single amino acid in a single CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (entire article, Abstract).)
Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies not having all of the relevant functional complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Claims 11-13 are rejected under 35 U.S.C. 112, first paragraph, as containing 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.
Applicant broadly claims a host cell or expression vector or nucleic acid containing the nucleic acids of claims 11-13. The claims read on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the host cell, polynucleotide, or expression vector.
With respect to the unisolated host cells and transgenes as “polynucleotide” or “expression vectors” of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the antibody and antibody fragments of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 183-191). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming arguendo a person having ordinary skill in the art could make a host organism with functional transgene that encodes the instantly recited SEQ ID NO: 1, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by expressing proteins, such as therapeutic antibodies. In a transgenic cell or animal that expresses the same, the antibody will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nature Reviews Drug Discovery, Vol. 9, Pg. 325-337, 2010) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. The instantly encoded antibody binds a mammalian protein and so may very well target related or unrelated proteins in the transgenic host, leading to such side effects. For all these reasons, previously raised and new, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "host cell" and by amending the vector and polynucleotide claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use transgenic animals possessing the claimed host cells, nucleic acid, or expression vector, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed host cell, nucleic acid, or expression vector, commensurate in scope with the claimed invention. The same can be said for the transgenes and transgenic animals encompassed by the instant claims. Thus, the claims are rejected here.
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 1-15 and 18-20 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 1-11, 14 and 18 recite the limitation "antibody". Claims 12, 13, 15, 19 and 20 are also rejected because they depend from these claims above, but do not remedy this deficiency.
This limitation is unclear because "antibody" is defined as: "In the present invention, the term "antibody" refers to a protein molecule acting as a receptor that specifically recognizes an antigen, including immunoglobulin molecules that are immunologically reactive with a specific antigen, and includes polyclonal antibodies, monoclonal antibodies, whole antibodies, and antibody fragments." [see page 7 of specification] Therefore, the word "antibody" includes monoclonal (mAb) and polyclonal antibodies (pAb) or fragments thereof. Therefore, the claim encompasses polyclonal antibodies with the six CDRs. However, polyclonal antibodies have many and different antibody species. The CDRs or variable regions could be found on one molecule in the pAb or two. The claim can be clarified by the following claim amendments: adding "monoclonal" to the limitation.
Appropriate correction is required. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI
2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim
is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the
applicant to more precisely define the metes and bounds of the claimed invention by holding the
claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claims 5 and 6 recite, “The antibody according to claim 1, comprising: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5; and (b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, a heavy chain CDR2 of SEQ ID NO: 8, and a heavy chain CDR3 of SEQ ID NO: 9.” and “The antibody according to claim 1, comprising: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 6; and (b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 10, a heavy chain CDR2 of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 13.”, respectively.
Claim 10 recites, “comprising a light chain variable region represented by SEQ ID NO: 14; and a heavy chain variable region represented by SEQ ID NO: 16”.
However, the recitation of “including a light chain CDR 1 of SEQ ID NO: 3” is indefinite because the recitation of “including a…” includes CDRs comprising fragments of the disclosed SEQ ID NO:” Therefore, it is unclear if this limitation is exclusively drawn to the CDR of SEQ ID NO: 3 or a fragment thereof. This issue also applies to the other claimed CDRs in claims 5 and 6 and the variable region limitations of claim 10 are also unclear for these reasons.
The claims can be made clearer if they are amended to recite, [claim 5] “The antibody according to claim 1, comprising: (a) a light chain variable region including the light chain CDR1 of SEQ ID NO: 3, the light chain CDR2 of SEQ ID NO: 4, and the light chain CDR3 of SEQ ID NO: 5; and (b) a heavy chain variable region including the heavy chain CDR1 of SEQ ID NO: 7, the heavy chain CDR2 of SEQ ID NO: 8, and the heavy chain CDR3 of SEQ ID NO: 9.” and [claim 6] “The antibody according to claim 1, comprising: (a) a light chain variable region including the light chain CDR1 of SEQ ID NO: 3, the light chain CDR2 of SEQ ID NO: 4, and the light chain CDR3 of SEQ ID NO: 6; and (b) a heavy chain variable region including the heavy chain CDR1 of SEQ ID NO: 10, the heavy chain CDR2 of SEQ ID NO: 12, and the heavy chain CDR3 of SEQ ID NO: 13.”, and [claim 10] “comprising the light chain variable region represented by SEQ ID NO: 14; and the heavy chain variable region represented by SEQ ID NO: 16”.
Claims 5 and 6 recite, “The antibody according to claim 1, comprising: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5; and (b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, a heavy chain CDR2 of SEQ ID NO: 8, and a heavy chain CDR3 of SEQ ID NO: 9.” and “The antibody according to claim 1, comprising: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 6; and (b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 10, a heavy chain CDR2 of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 13.”, respectively. Claims 2-4 also recite CDRs that are indefinite for reasons set forth below.
However, the CDR identification is indefinite because the numbering system used to identity the
For instance, Figure 6 of Dondelinger et. al. (Dondelinger M, et. al. Front Immunol. 2018 Oct 16;9:2278.) illustrates the issue. If a sequence of SEQ ID NO: 1 is provided for the VH chain, the CDRs would be different depending on what numbering system is used. Say the claims are drawn to an antibody that consists of a CDR1 of SEQ ID NO: 3(SGSAMH) (CDR identified with Martin numbering and Contact definition schema), wherein the longer antibody sequence is that of SEQ ID NO:1. Using a program or online tool such as AbRSA (http://cao.labshare.cn/AbRSA/abrsa.php) or NovoPro (https://www.novoprolabs.com/tools/cdr), a skilled artisan can identify the CDR regions in a longer antibody sequence that at least consists of a variable heavy (VH) or variable light (VL) chain complete sequence.
*Under Chothia numbering, an antibody with a VH of SEQ ID NO:2 would have its CDRs identified as the following:
EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYXMSWVRQAPGKGLEWVSXISQSGGYTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVIYASLDYWGQGTLVTVSS
*CDRs identified by applicant (SEQ ID NO:s 10, 12 and 13, respectively):
EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYXMSWVRQAPGKGLEWVSXISQSGGYTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVIYASLDYWGQGTLVTVSS
*Under Kabat numbering, an antibody with a VH of SEQ ID NO:1 would have its CDRs identified as the following:
EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYXMSWVRQAPGKGLEWVSXISQSGGYTNYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVIYASLDYWGQGTLVTVSS
As one can see, the antibody with a VH of SEQ ID NO:2 under Kabat numbering has a CDR1 which consists of TYXMSW, while the CDR1 using Chothia numbering consists of GFTFSTY. Neither therefore would be infringing upon the antibody with a CDR1 that consists of TYXMS, even though all three of these sequences were found within the same VH region of the same antibody. Therefore, providing the CDR sequences without providing the numbering system used to identify said sequences within the claim is insufficient, as one of skill in the art is not clear as to the metes and bounds of the claimed invention.
Claim 15 recites the limitation "composition" in line 2 twice. There is insufficient antecedent basis for this limitation in the claim. Amending the claim to recite, “pharmaceutical composition” in place of “composition” will overcome this rejection.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 7, 14, 15 and 18-20 are rejected under 35 U.S.C. 102a1 as being anticipated by Budkowska et al. (Hepatology, 1992, Vol. 15, Pages 26-31).
The claimed invention is drawn to an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19. Wherein the antibody specifically binds to one or more genotypes selected from HBV genotype A, B, C, D, E, F, G or H.
MPEP § 2112 (II) recites, “INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE RELEVANT TIME There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference”
Therefore, if the prior art teaches a mixture of antibodies that are capable of binding to the PreS1 protein of HBV, then the prior art would anticipate the antibody of claim 1 and the additional ability to binding to a HBV of genotype A, B, C, D, E, F, G or H (claim 7).
MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.”
The antibody is also part of a pharmaceutical composition for treatment or prevention of HBV infection; or the antibody is part of a composition comprising the antibody, which is for detection or diagnosis of HBV or is part of a kit for detection of HBV. In view of the guidance from MPEP 2111.02 II, the limitations of “for prevention or treatment of HBV infection”, “for detection of HBV”, “for diagnosis of hepatitis B” are interpreted as intended use limitations. Additionally, the recitation of a “kit” does not also require an additional component, therefore, the antibody is the kit.
Budkowska et al. teach the collection of sera from humans infected with HBV. The sera was analyzed for antibodies specific for PreS1. [see page 27 and right column of page 28] This sera is a mixture of monoclonal antibodies (i.e., a polyclonal solution) and some of the samples from the infected humans contained antibodies specific for PreS1 and PreS2. [see Table 1 and first 2 paragraphs of Results section] Therefore, the sera that contains these antibodies includes an antibody that would inherently be specific for the preS1 antigen at a position corresponding to positions 22, 23, and 25 based on SEQ ID NO: 19 and capable of binding a HBV of genotype A, B, C, D, E, F, G or H.
Therefore, Budkowska et al. anticipate the instant invention.
Claim(s) 1, 7, 11-15 and 18-20 are rejected under 35 U.S.C. 102a1 as being anticipated by Jo et al. (Journal of Microbiology and Biotechnology, Vol. 28, No. 8, pages 1376-1383).
The claimed invention is drawn to an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19. Wherein the antibody specifically binds to one or more genotypes selected from HBV genotype A, B, C, D, E, F, G or H.
MPEP § 2112 (II) recites, “INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE RELEVANT TIME There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference”
Therefore, if the prior art teaches a mixture of antibodies that are capable of binding to the PreS1 protein of HBV, then the prior art would anticipate the antibody of claim 1 and the additional ability to binding to a HBV of genotype A, B, C, D, E, F, G or H (claim 7).
MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.”
The antibody is also part of a pharmaceutical composition for treatment or prevention of HBV infection; or the antibody is part of a composition comprising the antibody, which is for detection or diagnosis of HBV or is part of a kit for detection of HBV. In view of the guidance from MPEP 2111.02 II, the limitations of “for prevention or treatment of HBV infection”, “for detection of HBV”, “for diagnosis of hepatitis B” are interpreted as intended use limitations. Additionally, the recitation of a “kit” does not also require an additional component, therefore, the antibody is the kit.
The claimed invention also requires a polynucleotide encoding the antibody, an expression vector that comprises the polynucleotide and a host cell that comprises the expression vector.
Jo et al. teach generation of an antibody Fab by using a Fab phage library and panned it against HBV preS1 proteins (GST-pres1(1-119), GST-preS1(1-56), Bio-preS1-L peptide, and preS1 (1-119) of genotype C HBV. [see Materials and Method] Selected Fab were converted into IgG1 using PCR and subcloned into expression plasmids, which were introduced into HEK 293F cells. [Thereby anticipating claims 11-13] A monoclonal antibody produced was named 1A8 and tested for its ability to bind to different PreS1 proteins of different HBV genotypes [see Figure 3B]
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In addition, Figure 4 [below] establishes the binding specificity of 1A8 for the preS1 (1-56) peptide.
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Jo et al. also teach “amino acids 20–26 of preS1 play an essential role in the interaction with the cellular receptor sodium taurocholate cotransporting polypeptide (NTCP) and mediate HBV infection [5, 6]. This essential region is highly conserved among HBV genotypes (Fig. 1-below), making it a potential target for the prevention and treatment of HBV infection.” [see Introduction section]
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Jo et al. also teach that their research “suggest that 1A8 recognizes amino acids 20–25 in the receptor-binding motif and, thus, neutralizes HBV infection by blocking the preS1-NTCP interaction.” [see Discussion section] The highlighted amino acid sequence in figure 1 “NPLGFFP” is the same highlighted sequence found in Figure 1 of the instant application.
Therefore, Jo et al. anticipate the instant invention.
Claim(s) 1-15 and 18-20 are rejected under 35 U.S.C. 102a1 as being anticipated by Jo et al. (supra), as evidenced by Hong et al. (Vaccines, 2021, Vol. 8, pages 1-12).
The claimed invention is drawn to an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19. Wherein the antibody specifically binds to one or more genotypes selected from HBV genotype A, B, C, D, E, F, G or H.
The antibody has tyrosine at position 8 in an LCDR3 sequence of SEQ ID NO: 5 and leucine at position 6 in an HCDR3 sequence of SEQ ID NO: 9 as paratopes;
or
the antibody has amino acid at position 1 in an HCDR2 sequence represented by SEQ ID NO: 8 as a paratope and the amino acid residue at position 1 in the HCDR2 sequence represented by SEQ ID NO: 8 is alanine or serine;
or
the antibody comprises: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5, which includes the more specific CDR of SEQ ID NO: 6; and
(b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, which includes the more specific CDR of SEQ ID NO:10, a heavy chain CDR2 of SEQ ID NO: 8, which includes the more specific CDR of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 9, which includes the more specific CDR of SEQ ID NO: 13;
or
the antibody consists of the light chain variable region of SEQ ID NO: 1;
or
the antibody consists of the heavy chain variable region of SEQ ID NO: 2;
or
the antibody comprises a light chain variable region represented by SEQ ID NO: 14 and a heavy chain variable region represented by SEQ ID NO: 16.
The claimed invention also requires a polynucleotide encoding the antibody, an expression vector that comprises the polynucleotide and a host cell that comprises the expression vector.
MPEP § 2112 (II) recites, “INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE RELEVANT TIME There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference”
Therefore, if the prior art teaches a mixture of antibodies that are capable of binding to the PreS1 protein of HBV, then the prior art would anticipate the antibody of claim 1 and the additional ability to binding to a HBV of genotype A, B, C, D, E, F, G or H (claim 7).
MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.”
The antibody is also part of a pharmaceutical composition for treatment or prevention of HBV infection; or the antibody is part of a composition comprising the antibody, which is for detection or diagnosis of HBV or is part of a kit for detection of HBV. In view of the guidance from MPEP 2111.02 II, the limitations of “for prevention or treatment of HBV infection”, “for detection of HBV”, “for diagnosis of hepatitis B” are interpreted as intended use limitations. Additionally, the recitation of a “kit” does not also require an additional component, therefore, the antibody is the kit.
Jo et al. teach generation of an antibody Fab by using a Fab phage library and panned it against HBV preS1 proteins (GST-pres1(1-119), GST-preS1(1-56), Bio-preS1-L peptide, and preS1 (1-119) of genotype C HBV. [see Materials and Method] Selected Fab were converted into IgG1 using PCR and subcloned into expression plasmids, which were introduced into HEK 293F cells. [Thereby anticipating claims 11-13] A monoclonal antibody produced was named 1A8 and tested for its ability to bind to different PreS1 proteins of different HBV genotypes [see Figure 3B]
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In addition, Figure 4 [below] establishes the binding specificity of 1A8 for the preS1 (1-56) peptide.
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Jo et al. also teach “amino acids 20–26 of preS1 play an essential role in the interaction with the cellular receptor sodium taurocholate cotransporting polypeptide (NTCP) and mediate HBV infection [5, 6]. This essential region is highly conserved among HBV genotypes (Fig. 1-below), making it a potential target for the prevention and treatment of HBV infection.” [see Introduction section]
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Jo et al. also teach that their research “suggest that 1A8 recognizes amino acids 20–25 in the receptor-binding motif and, thus, neutralizes HBV infection by blocking the preS1-NTCP interaction.” [see Discussion section] The highlighted amino acid sequence in figure 1 “NPLGFFP” is the same highlighted sequence found in Figure 1 of the instant application.
As evidenced by Hong et al., the monoclonal antibody 1A8 of Jo et al. is the same antibody presently claimed that possesses the claimed CDR sequences of SEQ ID NO:s 3, 5, 6, 10, 12 and 13 and the variable chain regions of SEQ ID NO:s 14 and 16, which is capable of binding the preS1 at an epitope comprising a Leucine at position 22, a Glycine at position 23 and a Phenylalanine at position 25, corresponding to SEQ ID NO: 19.
Hong et al. teach the same monoclonal antibody 1A8 of Jo et al. and tested the ability of this antibody to bind to preS1 peptides of HBV that possessed amino acid mutations at residues within positions 20-26 [see figure 2 below]. Specifically, Hong et al. states “Regarding the results, 1A8 recognized the three residues (Leu22, Gly23, and Phe25) within the receptor-binding motif (NPLGFFP), while four CDR residues of 1A8 were critical in antigen binding.” [see introduction] Hong et al. also teach that 1A8 has a “…Leu100 in the HCDR3 and Tyr96 in the LCDR3 are in the paratope of 1A8, which directly contact the epitope.” [see section 3.2] and “Since we identified the fine epitope (Leu22, Gly23, and Phe25 of preS1) and paratope (Leu100 in the HCDR3, Tyr96 in the LCDR3, Ala33 in the HCDR1, and Ser50 in the HCDR2)of 1A8…” [see section 3.5] [which are requirements of claims 2-4].
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In comparison to the instant invention, figure 6 (see below) presents binding affinity of the antibody AbS0. However, this binding affinity appears to be the same as Figure 2 of Hong et al.
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In addition, the experimental method used by applicant (see working examples 2 and 3 of the specification appear to be the same as those carried out by Jo et al. Therefore, the monoclonal antibody 1A8 of Jo et al. appears to be the same antibody as AbS0 based on the methods used by Jo et al. to generation the 1A8, the CDR information of 1A8 confirmed by Hong et al. and the binding specificity of residues Leu22, Gly23 and Phe25 of the PreS1 peptide which is also bound by antibody AbS0. While Jo et al. and Hong et al. do not provide the amino acid sequences of the CDRs or variable chain regions, since the monoclonal antibody 1A8 is the same as AbS0, these amino acid sequences are inherent to the antibody of 1A8.
Therefore, Jo et al., as evidenced by Hong et al. anticipate the instant invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-15 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Jo et al. (supra), as evidenced by Hong et al. (supra), and further in view of Bogdanoff et al. (ACS Infect. Dis. 2016, Vol. 2, pages 313-321).
The claimed invention is drawn to an antibody that binds to an amino acid at a specific position in a preS1 antigen of HBV (hepatitis B virus), wherein the specific position in the preS1 antigen corresponds to positions 22, 23, and 25 based on SEQ ID NO: 19. Wherein the antibody specifically binds to one or more genotypes selected from HBV genotype A, B, C, D, E, F, G or H.
The antibody has tyrosine at position 8 in an LCDR3 sequence of SEQ ID NO: 5 and leucine at position 6 in an HCDR3 sequence of SEQ ID NO: 9 as paratopes;
or
the antibody has amino acid at position 1 in an HCDR2 sequence represented by SEQ ID NO: 8 as a paratope and the amino acid residue at position 1 in the HCDR2 sequence represented by SEQ ID NO: 8 is alanine or serine;
or
the antibody comprises: (a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5, which includes the more specific CDR of SEQ ID NO: 6; and
(b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, which includes the more specific CDR of SEQ ID NO:10, a heavy chain CDR2 of SEQ ID NO: 8, which includes the more specific CDR of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 9, which includes the more specific CDR of SEQ ID NO: 13;
or
the antibody consists of the light chain variable region of SEQ ID NO: 1;
or
the antibody consists of the heavy chain variable region of SEQ ID NO: 2;
or
the antibody comprises a light chain variable region represented by SEQ ID NO: 14 and a heavy chain variable region represented by SEQ ID NO: 16.
The claimed invention also requires a polynucleotide encoding the antibody, an expression vector that comprises the polynucleotide and a host cell that comprises the expression vector.
MPEP § 2112 (II) recites, “INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE RELEVANT TIME There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference”
Therefore, if the prior art teaches a mixture of antibodies that are capable of binding to the PreS1 protein of HBV, then the prior art would anticipate the antibody of claim 1 and the additional ability to binding to a HBV of genotype A, B, C, D, E, F, G or H (claim 7).
MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.”
The antibody is also part of a pharmaceutical composition for treatment or prevention of HBV infection; or the antibody is part of a composition comprising the antibody, which is for detection or diagnosis of HBV or is part of a kit for detection of HBV. In view of the guidance from MPEP 2111.02 II, the limitations of “for prevention or treatment of HBV infection”, “for detection of HBV”, “for diagnosis of hepatitis B” are interpreted as intended use limitations. Additionally, the recitation of a “kit” does not also require an additional component, therefore, the antibody is the kit.
The teachings of Jo et al. and Hong et al. are summarized above, however, they do not explicitly provide the amino acid sequences of the:the antibody comprises:
(a) a light chain variable region including a light chain CDR1 of SEQ ID NO: 3, a light chain CDR2 of SEQ ID NO: 4, and a light chain CDR3 of SEQ ID NO: 5, which includes the more specific CDR of SEQ ID NO: 6; and
(b) a heavy chain variable region including a heavy chain CDR1 of SEQ ID NO: 7, which includes the more specific CDR of SEQ ID NO:10, a heavy chain CDR2 of SEQ ID NO: 8, which includes the more specific CDR of SEQ ID NO: 12, and a heavy chain CDR3 of SEQ ID NO: 9, which includes the more specific CDR of SEQ ID NO: 13;
and variable chain regions:the antibody consists of the light chain variable region of SEQ ID NO: 1;
or
the antibody consists of the heavy chain variable region of SEQ ID NO: 2;
or
the antibody comprises a light chain variable region represented by SEQ ID NO: 14 and a heavy chain variable region represented by SEQ ID NO: 16.
Bogdanoff et al. teach an analytical method for determining the amino acid sequence of a known monoclonal antibody (PL-2). [see abstract and page 315] By using protease digestions and high resolution tandem mass spectrometry, the full sequence of PL-2 was determined. [see pages 315 and Figure 4]
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Jo et al., as evidenced by Hong et al., in order to determine the amino acid sequences of the CDRs and variable chain regions of monoclonal antibody 1A8 are the same as those presently claimed. One would have been motivated to do so, given the suggestion by Jo et al. that the 1A8 can be created through phage library screening and recombinant biotechnology procedures involving the nucleic acid sequences necessary to generate the monoclonal antibody 1A8. There would have been a reasonable expectation of success, given the knowledge that obtaining the amino acid sequence from a known antibody can be achieved through de novo sequencing by mass spectometry, as taught by Bogdanoff et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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