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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on July 14, 2026 is acknowledged. The traversal is on the ground(s) that claim 67 depends from claim 53 and that claim 67 should be examined together with Group I. This argument is found persuasive, and claims 40-51, 53-62, 67, and new claim 73 are encompassed by Group I.
Applicant’s election without traverse of (A) PMEL17 antibody of heavy chain variable region comprising CDR1-3 of SEQ ID NOs: 1-3 and light chain variable region comprising CDR1-3 of SEQ ID NOs: 14-16 and (B) reducing agent as cysteine HCl in the reply filed on July 14, 2026 is acknowledged. After further consideration, species election B is withdrawn.
Claims 52, 64-66, and 68-72 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 40-51, 53-62, 67, and 73 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The application claims benefit to U.S. Provisional Application 62/783,565, filed December 21, 2018.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on January 3, 2024, May 21, 2024, and July 14, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
Specification Objections
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg 24, 27, and 32). 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.
Claim Objections
Claim 40-41 are objected to because of the following informalities:
Claims 40-41 use acronyms without first defining what they represent in the independent claims (PMEL17 and TCEP). While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym. 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.
Claim 47 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 47 contains the trademark/trade name Sephadex. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a desalting column, and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112(a)
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 40-51, 53-62, 67, and 73 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Claims 40-51, 53-62, 67, and 73 are drawn to method of producing an anti-PMEL17 antibody. In claim 40, the antibody is defined entirely by function; i.e. the ability to bind PMEL17. Regarding claims 51 and 67, the combination of the six specific CDRs necessary to form the antigen binding domain of the anti-PMEL17 antibody is not set forth clearly to indicate which set of heavy chain CDRs and light chain CDRs are to be paired to create a functional PMEL17 binding domain. This leads to a pick and choose situation that leaves it up to the public to determine what the claimed antibody is. Multiple amino acid sequences are recited for each of the six CDRs in claims 51 and 67 subparts (a)-(nn). As such, the claims encompass a vast genus of antibodies that bind PMEL17 comprising numerous combinations of HCDR1-3 and LCDR1-3. It is appreciated that applicant has set forth related alternatives for each CDR, based on different CDR numbering systems. As claimed, however, the antibodies may be comprised of a combination of CDRs that lack the sufficient minimal structure to perform the required function, which is binding to PMEL17.
While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid deletions in the antigen-binding domains.
As detailed below, applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such, applicant’s disclosure does not satisfy the written description requirement of 30 U.S.C. 112(a).
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. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three complementarity determining regions that provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see Almagro et al, Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1; instant PTO-892).
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. See for example Kussie (instant PTO-892), who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-azophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (see abstract).
Furthermore, 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 (pg 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 pg 11).
As specificity of an antibody stems from the interaction of six CDRs, 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 comprises new antibodies, or at the least disclosure of new antibodies that could not have been envisaged from the prior art, which indicates that the prior art was not in possession of all anti-PMEL17 antibodies.
Thus, the prior art cannot provide sufficient written description of this genus of compounds and the specification as filed 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 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.
Regarding the antibody of instant claim 40, 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 of anti-PMEL17 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 (instant PTO-892), 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”).
According to the specification, the applicant has disclosed at least 20 species of anti-PMEL17 antibodies that comprise specific combinations of the claimed HCDR1-3 and LCDR1-3 amino acid sequences. Although applicant has disclosed numerous species within said genus of PMEL17 antibodies, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish most of the members comprised within the genus claimed, specifically which six CDR amino acids sequences from the recited CDRs should be combined to yield an antigen-binding region that is capable of binding PMEL17.
There is no way to determine if these antibodies represent the full breadth of what is claimed. The disclosure of these specific antibodies would not convey to the artisan that applicant was in possession of the full genus of all antibodies which possess the required function nor does it allow the skilled artisan to envisage the specific structure of such antibodies.
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of antibodies that bind PMEL17. 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).
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.
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 of the elements 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.
For claims drawn to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011). An antibody described only by functional characteristic, such as antibody that binds PMEL17, 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).
With the exception of specifically disclosed antibodies with specific CDRs, 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).
Therefore, claims 40-51, 53-62, 67, and 73 do not meet the written description requirement.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 40-42 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 20160130358, published May 12, 2016 (“Bhakta”; instant PTO-892).
Bhakta teaches a method for generating cysteine engineered antibodies comprising free cysteines in the heavy or light chain [0008]. Cysteine adducts are reductively cleaved with a reducing agent such as DTT or TCEP to give a reduced form of the antibody [0570], and the interchain disulfide bonds between paired cysteine residues are reformed under partial oxidation conditions [0569]-[0570], which reads on claims 40-42. In one embodiment, the antibody binds to PMEL17 [0021], which reads on claim 40.
Bhakta anticipates the method of claims 40-42 comprising the steps of (a) providing an anti-PMEL17 antibody, (b) contacting the antibody with a reducing agent DTT or TCEP, and (c) incubating the reduced antibody under oxidation conditions.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 40-50 are rejected under 35 U.S.C. 103 as being unpatentable over US 20160067351, published March 10, 2016 (“Geierstanger”; IDS from 7/14/2026) in view of Chen et al, published July 13, 2012 (IDS from 1/3/2024).
The claims are drawn to a method of producing a re-oxidized antibody that binds PMEL17.
Geierstanger teaches a method of modifying antibodies for the preparation of antibody-drug conjugates (ADCs) [0001], the method comprising contacting an antibody containing engineered cysteines with a reducing agent and then incubating the reduced antibody under oxidation conditions ([0006], [0012], [0469]-[0470]), as in instant claim 40. In the method of Geierstanger, all native disulfide bonds and the disulfide bonds between the cysteine adducts of the engineered cysteine residues of the antibody are reduced [0469], as in claims 40 and 50. To reduce cysteine, DTT was added to the antibody at a final concentration of 20 mM at 37° C for 1 hour [0469], as in claims 41-43. The mixtures were thendialyzed at 4° C against PBS for three days with daily buffer exchange to remove DTT and re-oxidize the native disulfide bonds [0469], as in claims 44-45. In another embodiment, the reducing reagents may be removed through a desalting column, Sephadex G-25 [0469], as in claims 46-47. Once the protein is fully reduced, 1 mM oxidized ascorbate (dehydro-ascorbic acid) is added to the desalted samples and the re-oxidation incubations are carried out for 20 hours [0469], as in claims 48-49.
Geierstanger does not teach a method for the re-oxidation of an anti-PMEL17 antibody, as required by the claims.
Chen et al teaches that PMEL17 is a pigment-forming protein (pg 24083-24084) that is highly expressed in skin and melanoma cell lines relative to other human tissues and human cancer cell lines (figure 1). PMEL17 is presented transiently at the cell surface prior to its entry into stage I melanosomes, and Chen finds that internalization and routing of cell-surface PMEL17 make it amenable to targeting with an antibody drug conjugate (pg 24083). Indeed, Chen et al demonstrates that PMEL17 antibody drug conjugates exhibit target-dependent killing of tumor cells in vitro and in vivo (abstract).
Given that Geierstanger teaches the method for producing a re-oxidized antibody and further given that Chen et al teaches the utility of anti-PMEL17 antibody drug conjugates for the treatment of melanoma, it would have been obvious to one of ordinary skill in the art to incorporate the anti-PMEL17 antibody of Chen et al in the Geierstanger method of producing a re-oxidized antibody. The motivation to do so comes from Chen et al, who teaches that PMEL17 expression is primarily limited to skin/melanoma cells and that an anti-PMEL17 antibody-drug conjugate for targeted delivery is less likely to impact antibody pharmacokinetics, which can be perturbed by dense target antigen sinks present in normal tissues (pg 24090). The modification of the method of Geierstanger to include an anti-PMEL17 antibody would have been a predictable use of a known targeting domain for its known purpose of improving specificity of the cytotoxic agent in the treatment of cancer. Such would amount to combining prior art elements according to known methods to yield predictable results, see MPEP 2143.
Claims 40-50, 53, and 56-62, are rejected under 35 U.S.C. 103 as being unpatentable over US 20160067351, published March 10, 2016 (“Geierstanger”; IDS from 7/14/2026) in view of Chen et al, published July 13, 2012 (IDS from 1/3/2024), as applied to claims 40-50 above, and further in view of WO 2018116178, published June 28, 2018 (“Wen”; instant PTO-892).
As discussed above, Geierstanger in view of Chen et al teach a method of producing a re-oxidized anti-PMEL17 antibody. These references do not teach the step wherein the reducing agent comprises reduced cysteines, as required by claims 53-62. Also, Geierstanger in view of Chen et al does not teach the limitation wherein the antibody is bound to a resin, as required by claims 53-62.
Wen teaches methods for making antibody drug conjugates, wherein the antibody is linked to a drug moiety [0006]. Antibodies with engineered cysteines were reduced and re-oxidized using an on-resin method, wherein the resin is Protein A [00362], as in claims 53 and 62. Protein A Sepharose beads were mixed with the antibody, and 20 mM cysteine was added to the mixture at room temperature for 30-60 min [00362], as in instant claims 53 and 57. The beads were washed with PBS for 30 min [00362], as in claim 56. Optionally, copper chloride at 50 nM to 1 mM was added to modulate the rate of re-oxidation [00362], as in the accelerant of claims 58-60. Since the addition of copper chloride is optional, Wen also teaches the limitation of claim 61 wherein step (c) does not comprise copper chloride.
Given that Geierstanger in view of Chen et al teach a method for producing re-oxidized anti-PMEL17 antibodies and Wen teaches a method for making antibody drug conjugate using a resin, it would have been obvious to one of ordinary skill in the art to apply the additional steps of binding the antibody to a resin and using reduced cysteine as the reducing agent, because these steps were known in the antibody drug conjugate art at the time the application was filed. One would use the method of Wen and have a reasonable expectation of successfully making a re-oxidized anti-PMEL17 antibody. Such amounts to application of a known technique (i.e. the method of Wen) to a known method ready for improvement (i.e. the method of Geierstanger in view of Chen et al) to yield predictable results, see MPEP2143.
Claims 40-50, 53-62, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over US 20160067351 (“Geierstanger”) in view of Chen et al and WO 2018116178 (“Wen”), as applied to claims 40-50, 53, and 56-62 above, and further in view of US 20170369567, published December 28, 2017 (“Heitzmann”; instant PTO-892).
As discussed above, Geierstanger in view of Chen et al and Wen teach a method of producing a re-oxidized anti-PMEL17 antibody. These references do not teach the limitation wherein the reducing agent is cysteine-HCl, as required by claims 54-55 and 73.
Heitzmann teaches methods for selectively reducing specific cysteine residues in an antibody (abstract). In the method of Heitzmann, the reducing agent for reducing cysteine residues in antibodies is “cysteine”, which includes cysteine and cysteine-HCl [0073], as in instant claims 54 and 73. The concentration of cysteine is 1.0-20 mM [0081], as in instant claims 54-55 and 73.
As Geierstanger in view of Chen et al and Wen teach the method of producing an oxidized anti-PMEL17 antibody and Heitzmann teaches a similar method comprising cysteine-HCl as the reducing agent, it would have been obvious to one of ordinary skill in the art to substitute the reducing agent of Geierstanger with the reducing agent and have a reasonable expectation of success. Such would amount to the simple substitution of one known element for another to obtain predictable results, see MPEP 2143.
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 40-51, 53-62, 67, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-55 of U.S. Patent No. 11,779,649 in view of US 20160067351 (“Geierstanger”), WO 2018116178 (“Wen”), and US 20170369567, published December 28, 2017 (“Heitzmann”; instant PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to the same anti-PMEL17 antibody (same SEQ ID NOs for instant claims 51 and 67) in a method of producing an antibody-drug conjugate.
Claims 1-3 of ‘649 teach the anti-PMEL17 antibody and claim 4 is drawn to the antibody comprising one or more cysteine substitutions, as in the providing an anti-PMEL17 antibody comprising cysteine step of instant claim 40. Claim 55 of ‘649 teaches a process for producing an anti-PMEL17 antibody drug conjugate, the steps comprising conjugating a linker-drug moiety to the anti-PMEL17 antibody.
The claims of ‘649 do not teach a method of producing a re-oxidized antibody, which is the step preceding the conjugation step.
Geierstanger teaches a method of modifying antibodies for the preparation of antibody-drug conjugates (ADCs) [0001], the method comprising contacting an antibody containing engineered cysteines with a reducing agent and then incubating the reduced antibody under oxidation conditions ([0006], [0012], [0469]-[0470]), as in instant claim 40. In the method of Geierstanger, all native disulfide bonds and the disulfide bound between the cysteine adducts of the engineered cysteine residues of the antibody are reduced [0469], as in claims 40 and 50. To reduce cysteine, DTT was added to the antibody at a final concentration of 20 mM at 37° C for 1 hour [0469], as in claims 41-43. Next, the mixtures were dialyzed at 4° C against PBS for three days with daily buffer exchange to remove DTT and re-oxidize the native disulfide bonds [0469], as in claims 44-45. Alternatively, the reducing reagents may be removed through a desalting column, Sephadex G-25 [0469], as in claims 46-47. Once the protein is fully reduced, 1 mM oxidized ascorbate (dehydro-ascorbic acid) is added to the desalted samples and the re-oxidation incubations are carried out for 20 hours [0469], as in claims 48-49.
Wen teaches methods for providing antibody drug conjugates, wherein the antibody is linked to a drug moiety [0006]. Antibodies with engineered cysteines were reduced and re-oxidized using an on-resin methods, wherein the resin is Protein A [00362], as in claims 53 and 62. Protein A Sepharose beads were mixed with the antibody, and 20 mM cysteine was added to the mixture at room temperature for 30-60 min [00362], as in instant claims 53 and 57. The beads were washed with PBS for 30 min [00362], as in claim 56. Optionally, copper chloride at 50 nM to 1 mM was added to modulate the rate of re-oxidation [00362], as in the accelerant of claims 58-60. Since the addition of copper chloride is optional, Wen also teaches the limitation of claim 61 wherein step (c) does not comprise copper chloride.
Given that the claims of ‘649 teach an anti-PMEL17 antibody drug conjugate and further given that Geierstanger, Wen, and Heitzmann teach methods for producing re-oxidized antibodies, it would have been obvious to one of ordinary skill in the art to apply the method of Geierstanger with the additional steps of Wen of binding the antibody to a resin and using the reducing agent cysteine HCl of Heitzman, because these steps and reducing agents were know in the antibody drug conjugate art at the time the application was filed. One would use and modify these methods and have a reasonable expectation of successfully re-oxidizing the anti-PMEL17 antibody of ‘649. Such amounts to application of a known techniques to known methods ready for improvement to yield predictable results, see MPEP2143.
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
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