Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07-10-2025 has been entered.
Claims 154-159, 162, 164-166, and 169-174 are pending. Claims 173-174 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 154-159, 162, 164-166, and 169-172 are pending and under consideration.
All rejections and or objections in the final rejection mailed 01/14/2025 are withdrawn in view of applicant’s arguments and amendments there to.
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 166 is 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 166 recites the limitation "the mutations" in claim 154. There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 158 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 158 refers back to the polypeptide of claim 154 wherein the polypeptide comprises the amino acid sequence set forth in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:158, SEQ ID NO:160, SEQ ID NO:162, or SEQ ID NO:164. However, SEQ ID Nos: 78, 80, 82, 84, 158, 160, 162, and 164 fail to further limit the polypeptide of Claim 154 because these sequences do not consist of the amino acids set forth in residues 1-245 of SEQ ID NO:47. Residue 6 of SEQ ID NO:47 is the amino acid glutamine as shown below:
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In contrast, SEQ ID Nos: 78, 80, 82, 84, 158, 160, 162, and 164 all contain glutamic acid or E at the same position. See for example SEQ ID NO: 78 and 160:
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Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of 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 169, and 171-172 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. This is a written description rejection.
Claim 169 is drawn to the heterodimeric PSMA-binding protein of claim 154 and a second polypeptide. The specification does not provide a definition or the metes and bounds of what this “second polypeptide” encompasses. For example, the specification teaches [0029] that the heterodimeric PSMA binding protein comprises a first polypeptide chain that comprises a “first binding” domain that specifically binds PSMA and a second single chain
polypeptide comprising, in order from amino-terminus to carboxyl-terminus, a second
hinge region, a second immunoglobulin sub-region, and a second immunoglobulin
heterodimerization domain that is different from the first immunoglobulin heterodimerization
domain of the first polypeptide chain, wherein the first and second immunoglobulin
heterodimerization domains associate with each other to form a heterodimer. The specification further teaches [0034] that in certain variations, a heterodimeric PSMA-binding protein as disclosed herein can be monospecific (i.e., monospecific for PSMA). Alternatively, in other embodiments, the heterodimeric PSMA-binding protein is multispecific. For instance, each polypeptide chain of the heterodimer can comprise different binding domains, e.g., the first polypeptide chain comprising the PSMA-binding domain and the second polypeptide chain comprising a second binding (e.g., amino-terminal to the second hinge region) that is specific for a second target antigen that is different from PSMA. Thus, the specification only appears to discuss a second polypeptide in the context of being physically associated with the heterodimeric PSMA-binding protein wherein the second polypeptide preferably binds PSMA or any other target antigen known or unknown. Hence, the second polypeptide is broadly drawn to an extremely large genus of proteins with binding or non-binding characteristics.
A description of a genus of may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus. However, the instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of “second polypeptides” that would distinguish the claimed proteins from other molecules that do not have the claimed biological properties. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the disclosure of a second protein with a domain that binds PSMA is insufficient to describe the large genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) clearly states “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). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of second polypeptides, 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 compound itself is required.
The written description in this case only sets forth a subgenus of second polypeptides; namely, those that bind PSMA as claimed in Claim 170. Thus, the written description is not commensurate in scope with the claims drawn to a genus of second proteins. In particular, the genus of the world of any “second protein” would be very large and highly diverse. The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., . An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
At present, the disclosure fails to describe the common attributes or characteristics that identify members of the genus. Thus, because the genus is highly variant, the contemplation of a world of “second proteins” is insufficient to describe the genus and one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
With the exception of a “second polypeptide that specifically binds PSMA”, the skilled artisan cannot envision the detailed structure of the encompassed proteins 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 a reference to a potential method of isolating it.
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 154-159, 162, and 164-166 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 7-11, and 16-17 of U.S. Patent No. 9782478 (Blankenship et al., Applicant’s IDS of 12-22-2020). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 154 is drawn to PSMA binding proteins with 6 CDRs comprising SEQ ID Nos 15, 16, 17 and 9, 10, and 11, a hinge region, a constant region, and a second binding domain that specifically binds CD3. Patented claim 1, although not identical, also claims a prostate-specific membrane antigen (PSMA)-binding polypeptide comprising a humanized PSMA-binding domain, a first hinge region, an immunoglobulin constant region and a second binding domain, wherein the PSMA binding domain comprises: (i) an immunoglobulin light chain variable region comprising LCDR1, LCDR2, and LCDR3, and (ii) an immunoglobulin heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein the LCDR1, LCDR2 and LCDR3 have the amino acid sequences set forth in SEQ ID NOs: 15, 16 and 17, respectively, and the HCDR1, HCDR2, and HCDR3 have the amino acid sequences set forth in SEQ ID NOs: 9, 10 and 11, respectively; wherein the second binding domain specifically binds a T cell receptor (TCR) complex or a component thereof. However, instant claim 158 further limits the polypeptide of instant claim 154 by distinctly defining the structures according to sequence identifiers:
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Likewise, patented Claim 8 (below) anticipates the identical sequences currently claimed in claim 158.
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Thus, both the invention of patented Claim 1 and the currently claimed bispecific (binds PSMA and CD3) polypeptide of claim 154 can have identical structures, including constant regions comprising immunoglobulin CH2 and CH3 domains of IgG1, IgG2, IgG3, or IgG4 (Compare instant claims 164-165) with patented claim 3. Also, patented claim 6 is drawn to first and second hinge regions which can be derived from a stalk region of a type II C lectin or an immunoglobulin hinge region. Instant claim 154 defines a hinge region comprising SEQ ID NO:99. Absent evidence to the contrary, SEQ ID NO:99 is derived from a stalk region of a type II C lectin or an immunoglobulin hinge region. As to claims 155 and 156, patented claims 16 and 17 encompass the same sequence identifiers. Regarding claim 159, it would have been obvious to one of ordinary skill in the art at the time the invention was made to swap the claimed domains that bound CD3 with other well-known CD3 binding domains such as SEQ ID NO:153 and 154 as these are well-known and exemplary anti-CD3 antibodies. See specification at [0062] and [0124]. As to claim 166, wherein the polypeptide of claim 154 has alterations in the first constant region that “decrease or eliminate” the ADCC cytotoxicity activity or Fc receptor-binding capability; such an activity is an inherent biological feature absent evidence to the contrary.
Claim Objections
Claim 170 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643