Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 4 and 14-28 are under consideration in the instant Office Action.
Claim Objections
Claims 16, 18 and 27 are objected to because of the following informalities: the claims contain multiple periods within each claim. For example, "a.". Please change format to "a)". Applicant's attention is directed to MPEP 608.01(m) that deals with claim format. In particular, MPEP 608.01(m) discloses that each claim begins with a capital letter and ends with a period. In addition, it is disclosed that periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 17 is rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 17 is indefinite because it uses the word “preferably”. Such language does not further limit the claim but potentially causes confusion over the claim scope. See MPEP § 2173.05(d) which states that “[d]escription of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim." Therefore, whatever is being claimed with exemplary language should either be explicitly claimed without the exemplary language or removed from the claim altogether.
Thus, the claim is indefinite because it is unclear whether it is limited to those options that follow the words “preferably”, or alternatively whether it includes the stated sequences.
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, 4 and 14-28 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.
The claims encompassed a genus of an anti-Sema3A antibodies to at least one amino acid residue within amino acid regions 37-382 of SEQ ID NO: 22 or wherein the antibody binds to SEQ ID NO: 21. Independent claims 14 and 24 call out specific CDR or heavy and light chain sequences but fail to claim the full antibody of all six specific CDRs or the heavy and light chain combinations. Rather, the claims call for half of the antibody. For example, claim 14 only requires heavy chain variable region or the light chain variable region. However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function the claimed antibodies or of treating a retinal disease, inhibiting the vasorespressive effect of SemaA3, improving revascularization or even the method of producing an anti-Sema3A antibody.
See MPEP §2163(I)(A) which states:
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
In this case, antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody. However, there is no way to a priori look at an antigen sequence (amino acid regions 37-382 of SEQ ID NO: 22 or wherein the antibody binds to SEQ ID NO: 21) and envisage the combination of six CDRs that will bind that antigen. Or only claiming half of a disclosed antibody. First, even highly related CDRs may not bind the same target. See for example Kussie et al., 1994 (IDS, 11/18/2024) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11).
Thus, the art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. As a further example, see Chen et al., 1995 (instant PTO-892) which demonstrates single amino acid changes in the VH CDR2 sequence can increase binding, decrease binding, destroy binding, or have no effect on binding when compared to the wild-type antibody.
See also Koenig et al., 2017 (instant PTO-892), which provides a large mutation analysis study where every amino acid in both variable regions are substituted with every other amino acid. Looking at figure 1 of Koenig, the bottom half of each section (labeled VEGF) relates to the ability of the mutant to bind the original target, with blue meaning a reduced affinity and black meaning a complete loss of binding ability. In VH-CDR2, for example, mutating any given residue to cysteine, which is encompassed by the instant claims, resulted in reduced binding at 12 residues and a complete loss of binding at 5 residues. That is, at 100% of the positions, mutation to cysteine reduced or ablated the antibody’s ability to bind the target. Looking at a specific position, in 100% of the mutations of residue 55, binding was reduced (15/19) or eliminated (4/19). While residues 56-65 appear more tolerant of change, residues 50-55 are generally intolerant of change.
It is appreciated that Koenig is studying one specific antibody and there is no evidence that the instant antibodies would react in the same way. However, this is part of the problem. It is entirely unclear from the specification which residues of Applicant’s CDRs are tolerant or intolerant to change, and whether those tolerant positions are only tolerant to conservative mutations. The fact that some residues might tolerate mutation does not convey to the skilled artisan that Applicant knew which of the claimed residues were tolerant of such, i.e., does not convey that Applicant was in possession of those sequences which are mutated yet preserve the claimed function. In other words, the specification fails to convey possession of an invention commensurate in scope with what is now claimed and therefore fails to meet the written description requirement. Looking at Koenig figure 2A, ~200 mutations in the CDR region of the VH chain completely abrogates any binding. While 2B appears to indicate that the CDRs of VL are more tolerant of change than the heavy chain CDRs, still over half of the mutations reduce binding compared to the parent.
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.
The specification discloses one species of anti-Sema3A antibody, i.e., clone I comprising the CDRs of SEQ ID Nos: 1-6. Table 1 of the specification at [0084 and 00107] disclose four anti-Sema3A variant antibodies (clones I to IV) directed against Sema3A with enhanced properties comprising the CDRs of SEQ ID Nos: 1-6. The specification at [00127] provides an anti-Sema3A antibody for treating retinal disease, wherein said antibody binds at least one amino acid residue within amino acid regions 370-382 of human Sema3A as set forth in SEQ ID NO: 22 or SEQ ID NO: 21. The instant specification provides one species of anti-Sema3A antibody, within the claimed genus of anti-Sema3A antibodies that treat retinal diseases. The specification fails to teach how half of the disclosed antibody, heavy or light chain or three CDRs, is capable of producing the required effects in the instantly claimed methods.
Also, see MPEP 2163 II(A)(3)(a))(ii): 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. 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
It is well known in the art that the epitope binding site of an antibody is usually defined by no more than six to eight amino acids. Neither the instant specification nor the art of record shows that the majority of antibodies that bind to any one of the multitude of epitopes present in a protein having amino acid 370-382 of human Sema3A are capable of treating thrombotic diseases, as is required for the operability of the claimed product. The required genus is not adequately described because neither the specification nor the art of record describes a representative number of species of antibody within the required genus.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Vas-Cath, Inc., v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. An antibody described only by functional characteristic, such as antibody that binds Sema3A or one of the claimed epitopes, without any known or disclosed correlation between that function and the structure of the sequence, is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995). In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody to demonstrate possession of the breadth of the genus Sema3 antibodies encompassed by the instant claims, especially in view of the unpredictability of such an endeavor. The prior art as evidenced by Edwards et al., 2003 (IDS 11/18/2024) teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Without this guidance or direction the skilled artisan would not consider applicant to be in possession of the claimed genus of antibodies because the skilled artisan recognizes that even seemingly minor changes made without guidance or direction as to the relationship between the particular amino acid sequence of the instantly claimed antibody and its ability to bind antigen, can dramatically affect antigen-antibody binding.
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of an antibody that binds human Sema3A. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 69 USPQ2d 1886 (Fed. Cir. 2004).
Further note the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. This decision has precipitated guidance to the Office instructing that the portion of MPEP 2163 regarding the “newly characterized antigen test” (indicating a well-characterized antigen is sufficient to satisfy written description for antibodies which bind that antigen) should no longer be used and that contrary materials should not be relied upon as reflecting the current state of the law. The method claims share the same issues as instant claims 1, 14, 22 and 24-26.. Further, the anti-Sema3A antibodies are required to practice the invention. The specification also fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of Sema3A as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
With respect to product claims, it is recognized that information which is well known in the art need not be described in detail in the specification (MPEP §2163(II)(A)(2)). See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed. MPEP §2163(II)(A)(3)(a) also discusses Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004), where a method of using a PGHS-2 inhibitor did not meet the written description as the inhibitor itself was not sufficiently described, clearly indicating that written description of the compound is still required in a method of using that compound. In this case, it is clear from the specification that the invention is in a new antibody, or at the least disclosure of a new antibody that could not have been envisaged from the prior art indicates that the prior art was not in possession of all “Sema3A antibodies”. Thus, the prior art cannot provide sufficient written description of this genus of compounds and the specification as filed, disclosing one antibody, does not sufficiently describe the genus either as there is an unknown amount of structurally distinct antibodies in this genus (see Amgen and Centocor decisions discussed above).
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of one generic, broad genus that encompassed a diverse and huge number of possible antibodies that bind the disclosed epitope. The specification does not provide a consistent structure for all of the possible antibodies and fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states 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 they invented what is claimed.” (See Vas-Cath at page 1116).
With the exception of specifically disclosed antibodies with the six specific CDRs or the light and heavy chain sequences encompassing the CDRS. in the instant specification, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claims 1, 4, 14-23 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 full antibody against Sema3A antibody with all six CDRs to treat specific retinal diseases associated with Sema3A, inhibiting the vasorepressive effect of SemaA3, improving revascularization of the retina, reducing the incidence of or ameliorating an eye or a retinal disease, does not reasonably provide enablement for the prevention of any eye or retinal disease with any anti-Sema3A antibody or any partially disclosed antibody (only three of the six required CDRs or light or heavy chains). 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 and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The instant claim 2 calls for a method of treating or preventing an eye or retinal disease by administering an anti-Sema3A antibody or an antigen-binding fragment
thereof that binds to at least one amino acid residue within amino acid regions 370-382 of human Sema3A, while instant claims 19-21 call for methods inhibiting the vasorepressive effect of SemaA3, improving revascularization of the retina and reducing the incidence of or ameliorating an eye or a retinal disease with an anti-Sema3A antibody that only requires half of the antibody; three CDRs or light chain variable region or heavy chain variable region. These methods as claimed do not require any specific antibodies except a general genus and at most discloses part of the structured antibody required in the treatment method to achieve the required function and results. The dependent claims call for undisclosed CDRs and light or heavy chains in any of the VH and VL and CDRs of the claimed antibody. The patient population is never narrowed in the instant claims 2, 19-21. The instant claims are broad and generic while what is enabled is narrow and specific. The instant specification only provides examples of upregulated levels of Sema3A in diabetic retinopathy (see [0205] Example 1). The specification provides a reasonable expectation of treating certain retinal degenerative disease with the disclosed antibody in Table 1, [0085]. The claimed treatments are targeted towards a general population with eye or retinal disease which is a very broad subject pool. While the treatment with the specifically disclosed antibody of Table 1, shows positive results in cell cultures, it still fails to show prevention in any eye or retinal treatment with the specifically disclosed antibody or even prevention with non-specific antibodies as set forth in the instant claims. The instant specification does not provide any examples or evidence that this type of treatment would provide a benefit with unknown and undisclosed antibodies. Further, the instant specification fails to teach any other possible antibodies that have the instantly claimed function and able to prevent any eye or retinal disease in a patient population. There is no support provided in the instant specification or in the prior or instant art that teaches or supports the ability prevent any disease.
The term “preventing” is generally understood in the art to encompass a total protection form 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 demonstrating any therapy using the claimed antibody, nor any examples directed to the palliative, preventative, or curative treatment of any inflammatory disease. 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 prevent of any eye or retinal disease.
Both at the time of filing and now, effective therapy for the prevention of any eye disease have eluded researchers. The instant specification itself does not teach any method of prevention of any eye or retina disease. The prior art Shirvan et al., 2002 (IDS, 11/18/2024) teaches that the use of polyclonal anti-Sema3A-derived peptides (Pep1A, corresponding to amino acids 363– 380 from chick Sema3A, and the control peptide Pep3A) antibodies, to rescue retinal ganglion cells (RGC) from cell death following optical nerve axotomy (see abstract and Antibody preparation). Shirvan teaches that the intravitreal administration of anti-Sema3A antibodies provided dramatic protection of retinal ganglion cells from axotomy-induced (injury) degeneration in the retina (see page 49805, top of 2nd column) but does not support the scope of preventing any eye disease or how half of an antibody is capable of producing the required method effects. Thus, the relevant art recognizes the unpredictability of methods directed to preventing any eye disease. The disclosure is not considered fully enabling for the claimed invention of prevention, since the state of the art teaches that prevention of any eye or retinal disease with any agent is not currently possible.
Claim 14 encompasses an antibody with unknown modifications, since it only requires part of the antibody to treat, improve or inhibit any of the possible diseases. The nature of the invention is clinical medicine comprising physiological modulation with an antibody for a medical disorder of the CNS, and is therefore of the highest complexity due to the complex nature of the central nervous system. The art does not provide compensatory teachings. The art teaches a limited amount of possible treatments to produce the limited result of effecting these types of diseases but does not teach the prevention of these types of diseases. Therefore, the prior art does not compensate for the failing of the instant specification. This speaks to the fact that while the art has observed possible antibodies that match the functional criteria of instant claims 2 and 19-21 that they have not yet identified all of the possible antibodies that read on the instant claims. There is still a lot of unknown in the art of what are all the possible antibodies that are functionally capable of meeting the functional imitations of the instant claims and would still require undue experimentation to determine what these antibodies are to prevent any eye or retinal disease. One of ordinary skill would also have to take into account what type of eye or retinal disease this antibody is being administered to, to be able to determine if the antibody meets the required function of the instantly claimed antibody and prevent these diseases. One of ordinary skill would also have to determine the full structure of the antibody since all of the claims only require part of the antibody and not the full six CDRs or the heavy or light chains required to make up a functioning antibody. This would require undue experimentation. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, the changes which can be made and still maintain activity/utility is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986).
As set forth above, inadequate guidance is presented in the specification to overcome the obstacles in practicing the claimed invention in its full scope. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. Given the tremendous breath of scope involving the instant claims, it would require undue experimentation for one of skill in the art to practice the claimed invention in its full scope. Therefore, the specification fails to provide enough guidance for one skilled in the art on how to practice the full scope of the instantly claimed method, thereby requiring trial and error experimentation to identify compounds meeting the functional limitations of the claims. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. One of skill in the art would neither expect nor predict the appropriate methods of treating all eye and retinal diseases in the manner claimed. Therefore, in view of the lack of guidance in the specification and in view of the discussion above, undue experimentation would indeed be required to make and use the invention commensurate with the scope of the claims.
The scope of the claims must bear a reasonable correlation with the scope of enablement. In re Fisher, 166 USPQ 18(CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Undue experimentation would be required to produce the invention commensurate with the breadth of the claims based on the disclosure of the instant specification and the knowledge in the art. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. In view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims, it would take undue trial and error to practice full scope of the claimed invention.
In conclusion, the instant claims encompass an invention of tremendous breadth, and essentially call for trial and error by the skilled artisan to begin discovering how to make the claimed invention without assisting the skilled artisan in such an endeavor, which amounts to undue experimentation and is therefore insufficient to constitute adequate enablement.
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.
Claims 1 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shirvan et al., 2002 (IDS, 11/18/2024).
Shirvan teaches that the use of polyclonal anti-Sema3A-derived peptides (Pep1A, corresponding to amino acids 363– 380 from chick Sema3A, and the control peptide Pep3A) antibodies, wherein the sequence of this peptide is identical in chick Sema3A, human semaphorin III, and rat and mouse semaphorin D to rescue retinal ganglion cells (RGC) from cell death following optical nerve axotomy (see abstract and Antibody preparation) and reads on instant claims 1 and 4. Shirvan teaches Sema3A antibodies at single doses for administration (see page 49804, top of 2nd column). Shirvan teaches that the intravitreal administration of anti-Sema3A antibodies provided dramatic protection of retinal ganglion cells from axotomy-induced (injury) degeneration in the retina (see page 49805, top of 2nd column) and reads on instant claim 4. Shirvan also teaches that their Sema3A antibodies would also treat glaucoma, retinal vein occlusion, occlusion of the central retinal artery and ischemic optic neuropathy (see abstract and page 49806, 2nd column, 2nd paragraph).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4 and 14-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,267,880. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘880 patent claims methods for inhibiting the vasorepressive effect of SemaA3 or methods for improving revascularization of the retina, comprising administering a pharmaceutically effective amount of the antibody or the antigen-binding fragment comprising: a heavy chain variable region comprising 100% sequence identity of the amino acid sequence of referenced and claimed SEQ ID NO: 1 (H-CDR1); the amino acid sequence of SEQ ID NO: 2 (H-CDR2); and the amino acid sequence of SEQ ID NO: 3 (H-CDR3); and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 (L-CDR1); the amino acid sequence of SEQ ID NO: 5 (L-CDR2); and the amino acid sequence of SEQ ID NO: 6 (L-CDR3) to a patient in need thereof, wherein said disease is selected from the group consisting of retinopathy, ischemic retinopathy, proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, diabetic macular edema, diabetic macular ischemia, age-related macular degeneration, retinitis pigmentosa, inherited retinal dystrophy, myopic degeneration, retinal artery occlusions (RVO), endophthalmitis, uveitis, cystoid macular edema, optic neuropathies, glaucoma, retinal detachment, toxic retinopathy, radiation retinopathy, traumatic retinopathy, drug-induced retinal vasculopathy, retinal neovascularization, polypoidal choroidal vasculopathy, retinal vasculitis, retinal microaneurysm, Fuch's dystrophy, macular telangiectasia, usher syndrome, and Stargardt disease, wherein said disease is selected from the group consisting of proliferative diabetic retinopathy, non-proliferative diabetic retinopathy, ischemic retinopathy, diabetic macular edema, diabetic macular ischemia, age-related macular degeneration, retinal neovascularization, glaucoma and choroidal neovascularization, wherein said disease is diabetic macular edema and/or diabetic macular ischemia, wherein: said disease is diabetic macular ischemia, and said antibody or an antigen-binding fragment promotes vascular regeneration within the ischemic retina (revascularization) and prevents pathological neovascularization of the vitreous region of the eye, wherein: said disease is diabetic macular edema, and said antibody or an antigen-binding fragment reduces permeability of blood retinal barrier, wherein said antibody or an antigen-binding fragment inhibits Sema3A-induced permeability of the blood retinal barrier.
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Claims 1, 4 and 14-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-25, 27-34,36-37 of copending Application No. 19/312,723. Although the claims at issue are not identical, they are not patentably distinct from each other because '723 claims methods for treating or preventing an eye or a retinal disease comprising administering a pharmaceutically effective amount of an anti-Sema3A antibody or the antigen-binding fragment wherein the anti-Sema3A antibody or an antigen-binding fragment thereof comprising: - a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1 (H-CDR1); the amino acid sequence of SEQ ID NO: 2 (H-CDR2); and the amino acid sequence of SEQ ID NO: 3 (H-CDR3); and - a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 (L-CDR1); the amino acid sequence of SEQ ID NO: 5 (L-CDR2); and the amino acid sequence of SEQ ID NO: 6 (L-CDR3) to a patient in need thereof , wherein said disease is a thrombotic disease of the retina that includes diabetic macular ischemia or diabetic macular edema and retinal vein occlusion. These antibodies and methods read on the instant claims that require the same Sema3A antibody and the same methods of treating retinal diseases of diabetic macular ischemia or diabetic macular edema and retinal vein occlusion through the same route of administration. Therefore, the claims of ‘723 anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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