Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
Claims 1-20 are pending.
Priority
The instant application claims priority to provisional application 63/511,711. Priority is given with the earliest effective filing date of 07/03/2023.
Drawings
The drawings are objected to because Figure 3 comprises color. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/19/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Objections
Claims 3 and 6 are objected to because of the following informalities: The claims recite an acronym (i.e. Fab, F(ab’)2, scFv, CD3) The first time an acronym is used, it must be accompanied by the definition of the abbreviation. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 3-4, 8-10, 13, 17, and 19-20 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation “an Fab fragment, an F(ab')2 fragment, an ScFv fragment.” A Fab, F(ab’)2, and scFv are fragments in and of themselves. Therefore, it is unclear if the claim intends to claim “a Fab, a F(ab’)2 an scFv” or intends to claim fragments of a Fab, a F(ab’)2 an scFv. Therefore, the scope of this claim is indefinite.
Claims 4 and 8-10 recite the limitation “at least about”. Applicant does not provide an explicit definition for “about”. Thus, the metes and bounds for “about” are dependent on the interpretation of others for determining what is an acceptable range.
Given a single value, one person of ordinary skill in the art could determine that the
value is acceptably in the range. Yet, another person of ordinary skill in the art
could determine that it is unacceptable, leading to two different interpretations on if the
claim infringes with “about.” Therefore, the scope of these claims is indefinite.
Claim 13 recites the limitation “a vector encoding the isolated antibody or antigen-binding fragment thereof.” A vector itself does not encode. Rather, a vector comprises a polynucleotide that encodes. Therefore, it is unclear how a vector without a polynucleotide can encode the antibody or antigen-binding fragment thereof. Thus, the scope of this claim is indefinite.
Claim 17 recites the limitation “a disease and/or disorder caused by or related to GRP78 activity or signaling.” The metes and bounds of “caused by or related to” are unclear. “Caused by” could be a direct causation or a downstream effect. “Related” is a relative term and therefore one could determine that a disease/disorder is related to GRP78, while another could determine that it is not related. Therefore, the scope of this claim is indefinite.
Claim 19 recites the limitation “a method for detecting expression of GRP78 or a cancer, comprising contacting the sample with the isolated antibody or antigen-binding fragment thereof of claim 1.” However, the claim does not require any detection steps or a process for making the antibody detectable and it is unclear how one would perform a method for detecting simply by contacting a sample with the antibody. Therefore, the scope of this claim is indefinite. Further, claim 19 lacks antecedent basis. The lack of antecedent basis arises from claim 19’s recitation of “the sample” and claim 19’s dependence from claim 1 where there is no mention of a “sample”.
Claim 20 recites the limitation “a kit for detecting GRP78 or a cancer in a sample, comprising the isolated antibody or antigen-binding fragment thereof of any of claim 1.” However, the claim does not require any other components in the kit for making the antibody detectable and it is unclear how one would be able to “detect” with only the antibody. Therefore, the scope of this claim is indefinite.
Claim Rejections - 35 USC § 112(a)
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-20 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.
Claim 1 is drawn to an isolated antibody or antigen-binding fragment thereof that is specific for an epitope in glucose regulated protein 78 (GRP78); wherein the isolated antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs) of a heavy chain variable region or CDRs of a light chain variable region, wherein the CDRs of the heavy chain variable region comprise: CDRH1 having the amino acid sequence of SEQ ID NO: 1, CDRH2 having the amino acid sequence of SEQ ID NO: 2, and CDRH3 having the amino acid sequence of SEQ ID NO: 3; and wherein the CDRs of the light chain variable region comprise: CDRL1 having the amino acid sequence of SEQ ID NO: 4, CDRL2 having the amino acid sequence of SEQ ID NO: 5, and CDRL3 having the amino acid sequence of SEQ ID NO: 6.
The instant specification teaches an antibody termed G2D03 that comprises SEQ ID NOs: 1-3 for the CDRH1-3, respectively, and SEQ ID NOs: 4-6 for the CDRL1-3, respectively [0081]. However, the specification does not teach a functional antibody containing only the three CDRs of the light chain variable region or only the three CDRs of heavy chain variable region.
In this case, claim 1 is drawn to a variable number of CDRs, e.g. either the three CDRs of light chain variable region or the three CDRs of the heavy chain variable region. The art recognizes that a complete set of six CDRs comprise the binding region of an antibody (see Sela-Culang et al., 2013; instant PTO-892), and that even a single amino acid change to these regions can completely abrogate the binding specificity of an antibody (see Kussie et al., 1994; instant PTO-892 and Chen et al., 1995; instant PTO-892). Thus, making changes to the CDR sequence of an antibody is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions. Thus, Applicant has failed to meet the written description of an isolated anti-GRP78 antibody that is able to bind GRP78 that comprises less than the full set of six CDRs of SEQ ID NOs: 4, 5, and 6 for the light chain variable region and SEQ ID NOs: 1, 2, and 3 for the heavy chain variable region.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held
that:
...To fulfill the written description requirement, a patent specification must
describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the
inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if
the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A
patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Thus, based on the teachings of the instant specification and the art, Applicant has failed to meet the written description of antibodies that are able to bind GRP78 that comprise less than the full set of six CDRs of SEQ ID NOs: 1-3 for the heavy chain variable region and SEQ ID NOs: 4-6 for the light chain variable region. Therefore, one of skill in the art would not conclude that Applicant was in possession of the antibodies that are able to bind GRP78 that comprise less than the full set of six CDRs.
Claims 2-20, which depend from claim 1, are therefore deficient for the same reasons above and do not meet the written description requirement.
Claim 3 is 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.
Claim 3 recites the “isolated antibody or antigen-binding fragment thereof of claim 1, which is…a humanized antibody or a human antibody.” Claim 3 depends from claim 1 which recites “an isolated antibody or antigen-binding fragment thereof that is specific for an epitope in glucose regulated protein 78 (GRP78); wherein the isolated antibody or antigen-binding fragment thereof comprises complementarity determining regions (CDRs) of a heavy chain variable region or CDRs of a light chain variable region, wherein the CDRs of the heavy chain variable region comprise: CDRH1 having the amino acid sequence of SEQ ID NO: 1, CDRH2 having the amino acid sequence
of SEQ ID NO: 2, and CDRH3 having the amino acid sequence of SEQ ID NO: 3; and
wherein the CDRs of the light chain variable region comprise: CDRL1 having the amino acid sequence of SEQ ID NO: 4, CDRL2 having the amino acid sequence of SEQ ID NO: 5, and CDRL3 having the amino acid sequence of SEQ ID NO: 6.
The specification states that the antibody comprising these specific CDRs is termed G2D03 [0081; Table 1] and that the G2D03 antibody is produced from a fully synthetic human scFv phage display [0116-0118]. Thus, it appears that the CDRs as claimed in claim 1, since they are produced from a fully human scFv phage display, would be human and the specification does not provide any other informative information. Because the disclosure in the specification is therefore describing the CDRs as claimed in claim 1 as human, then the antibody could not be humanized as claimed in instant claim 3. Therefore, claim 3 lacks written description for a “humanized” antibody as there is no disclosure how to humanize an antibody which is already human.
Note: if the CDRs recited in the claims are not from a human antibody, claim 3 would still lack written description for a “human” antibody because an antibody comprising CDRs from a species other than human cannot be “a human antibody”. This would not be considered a new ground of rejection as the issue is being raised currently. However, based on the instant specification, the source of the CDR sequences appears to be human.
Enablement
Claims 17-18 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 method of treating a GRP78 expressing cancer, does not reasonably provide enablement for treating any disease or disorder or prophylactically treating or preventing any disease or disorder caused by or related to GRP78 activity or signaling. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and
Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
The claims are drawn to a method for treating, prophylactic treating and/or preventing a disease and/or disorder caused by or related to GRP78 activity or signaling in a subject in need thereof, comprising administering a pharmaceutical composition to the subject in need thereof, wherein the pharmaceutical composition comprises an effective amount of the isolated antibody or antigen-binding fragment thereof of claim 1 and optionally a pharmaceutically acceptable carrier. Claim 18 adds the limitation wherein the disease is a cancer selected from the group consisting of lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, renal cell carcinoma, testicular cancer, melanoma, leukemia, and papillary thyroid cancer.
The claims are broad and inclusive of any type of disease or disorder that may be caused by or related to GRP78 activity or signaling. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The claims are extremely broad due to the vast number of possible diseases or disorders. The instant specification does not provide any evidence that the administration of the anti-GRP78 antibody or antigen-binding fragment thereof would treat and/or prevent any disease or disorder caused by or related to GRP78 activity or signaling.
Additionally, the terms “prophylactically treating” and “preventing” are generally understood in the art to encompass a total protection from disease or injury. Thus, given the high level of required effect, a high level of evidence showing prevention is also required. As noted above, however, there are no working examples in the instant specification directed to the palliative, preventative, or curative treatment of any disease or disorder. Therefore, the instant specification does not provide evidence or substantial guidance commensurate in scope with the broadly claimed method in how to use the method to prophylactically treat or prevent any disease or disorder.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
While the state of the art is relatively high with regard to treatment of specific diseases or disorders, such as specific cancer types encompassed by the instant claims, the state of the art with regard to treating or preventing any disease or disorder is underdeveloped. The instant specification itself does not teach any method or treatment that would treat or prevent any disease or disorder. One such disease encompassed by the broad claims is cancer. The cancer treatment art involves a very high level of unpredictability. While the state of the art is relatively high with regard to the treatment of specific cancers with specific agents, it has long been underdeveloped with regard to the treatment of cancers broadly. The lack of significant guidance from the present specification or prior art with regard to the actual treatment of all cancers with the claimed antibody makes practicing the claimed invention unpredictable.
With regard to cancer treatment, Bally et al. (US 5,595,756) stated, “Despite enormous investments of financial and human resources, no cure exists for a variety of diseases. For example, cancer remains one of the major causes of death. A number of bioactive agents have been found, to varying degrees, to be effective against tumor cells. However, the clinical use of such antitumor agents has been highly compromised because of treatment-limiting toxicities” [column 1, lines 17-24].
Furthermore, the art indicates the difficulties in going from in vitro to in vivo for drug development for treatment of cancers. Auerbach et al., 2000 (instant PTO-892) indicates that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response. For example, the 96 well rapid screening assay for cytokinesis was developed in order to
permit screening of hybridoma supernatants, and in vitro tests in general have been limited by the availability of suitable sources for endothelial cells, while in vivo assays have proven difficult to quantitate, limited in feasibility, and the test sites are not typical of the in vivo reality [page 167, left column, 1st paragraph].
Additionally, as taught by HogenEsch et al., 2012 (instant PTO-892), there is no single cell culture or in vivo cancer model that faithfully predicts the efficacy of anticancer drugs in human clinical trials. Cell culture approaches offer the advantage of human-derived cell lines or tissue fragments from primary tumors but cannot mimic the complexity of the reciprocal interaction between the growing tumor and the co-evolving microenvironment. Xenografts in immunodeficient mice have limited added value over cell culture models as the lack of an intact immune system and insufficient interactions between the human tumor cells and mouse stromal cells do not recapitulate human cancers [page 6; see Conclusion]. Thus, the art recognizes that going from in vitro studies to in vivo studies for cancer drug developments are difficult to achieve.
Finally, the art teaches the unpredictability of antibody-based cancer immunotherapy. Christiansen et al., 2004 (instant PTO-892) teaches numerous factors that inhibit successful therapeutic application of antibodies including low or heterogeneous expression of target antigens by tumor cells, high background expression of target antigen on normal cells, host antibody immune responses to the antibodies themselves, insufficient antitumor response after antibody binding, as well as significant physical barriers preventing antibody binding or delivery to a solid tumor mass, including the vascular endothelium, stromal barriers, high interstitial pressure, and epithelial barriers [see Abstract, page 1493, column 2, page 1496, column 1, last paragraph through page 1498, column 2]. Topp et al., 1998 (instant PTO-892) also teaches the complications and unpredictability involved with treating tumors using antibody therapy. Topp teaches that there are several barriers to successful delivery of antibody drugs to extravascular sites of action within target tissues: the antibody drugs must be absorbed into the blood stream, carried by the circulatory system to the capillaries in the target tissue, cross the capillary endothelial cells and the underlying basement membrane that supports the capillary structure and penetrate through the matrix of cells and extracellular components that comprises the tissue itself, bind to the cell surface receptor, initiate endocytosis, encounter possible drug degradation and drug release. Additional connective tissue barriers may also be encountered [page 15, both columns, and Figure 1]. While some antibody drugs have been shown to be effective in vitro the results of clinical trials have been disappointing. The inability of the antibodies to penetrate the tumor mass could be a cause of this lack of clinical efficacy. Topp cautions against extrapolating in vitro results to in vivo therapy stating that the cell culture system has some limitations including a lack of well-developed extracellular matrix (“stroma”) that is present in many tumors. Normal components of tumor stroma include collagen, fibronectin and glycosaminoglycans [page 21, column 2]. Given the unpredictable art of treating tumors in vivo using antibody therapy, one of skill in the art could not predictably treat cancer in vivo comprising administering any antibody without undue experimentation.
Given Bally’s teaching of treatment-limiting toxicities in clinical use, Auerbach’s teaching that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response, HogenEsch’s teaching that there is no single cell culture or in vivo cancer model that faithfully predicts the efficacy of anticancer drugs in human clinical trial, and Christiansen’s and Topp’s teachings of the unpredictability of antibody-based cancer immunotherapy, these teachings collectively demonstrate that the treatment of cancer is highly unpredictable.
(6) the amount of direction or guidance presented; (7) the presence or absence of working examples:
There is a lack of working examples in the specification for treating all diseases and disorders or prophylactically treating or preventing any disease or disorder caused by or related to GRP78 activity or signaling. Applicant has provided evidence that ovarian cancer, pancreatic cancer, melanoma, lung cancer, multiple myeloma, triple negative breast cancer, and liver bile duct carcinoma express GRP78 expression and the G2D03 antibody bound to the surface of the cancers [0137-0141]. However, Applicant has not provided any substantive evidence of treating any disease or disorder with the claimed antibody nor has Applicant provided any evidence of prophylactically treating or preventing any disease or disorder. Because the diseases and disorders encompassed by the instant claims are so disparate and no single example can be representative of all other diseases and disorders, a support of a given condition does not provide support for the breadth of the claims.
In conclusion, the claimed invention does not provide enablement for treating all diseases and disorders or prophylactically treating or preventing any disease or disorder. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Claims 19 is 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 method for detecting expression of GRP78 or detecting expression of GRP78 on a cancer, does not reasonably provide enablement for a method for detecting any cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and
Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
The claims are drawn to a method for detecting expression of GRP78 or a cancer, comprising contacting the sample with the isolated antibody or antigen-binding fragment thereof of claim 1.
The claims are broad and inclusive of detecting any cancer with the antibody or antigen-binding fragment that binds GRP78. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The claims are extremely broad due to the vast number of possible cancer types and tumor cell growth mechanisms represented by “a cancer”. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands.
(6) the amount of direction or guidance presented; (7) the presence or absence of working examples:
There is a lack of working examples in the specification for a method for detecting any cancer. Applicant has provided evidence that ovarian cancer, pancreatic cancer, melanoma, lung cancer, multiple myeloma, triple negative breast cancer, and liver bile duct carcinoma express GRP78 expression and the G2D03 antibody bound to the surface of the cancers [0137-0141]. Applicant has not provided any substantive evidence or detecting any cancer (e.g. those that do not express GRP78) with the claimed antibody. Because the cancers encompassed by the instant claims are so disparate and no single cancer example can be representative of all the other encompassed cancers, support of a specific example does not provide support for the breadth of the claims.
In conclusion, the claimed invention does not provide enablement for detecting all types of cancer encompassed by the instant claims. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, and the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
The art does not teach an anti-GRP78 antibody comprising the SEQ ID NOs: of 1, 2, and 3 for the CRRH1-3 of the heavy chain variable region and SEQ ID NOs: 4, 5, and 6 for the CDRL1-3 of the light chain variable region.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
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, Jeffrey Stucker can be reached at (571) 272-0911. 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.
/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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