DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/4/2026 has been entered.
Notice of Pre-AIA or AIA Status
2. The present application is being examined under the pre-AIA first to invent provisions.
3. Claims 2-4, 6-12 and 14-22 are pending. Claims 21-22 are new. Claims 1, 5 and 13 are canceled. Claims 2-4, 12, 14-15 and 18 have been amended.
4. Claims 2-4, 6-12 and 14-22 are under examination.
5. The status of claims 4 and 15 (withdrawn) is incorrect as the claims have been examined in the previous office actions.
Priority
6. In view of applicant’s amendments to the claims to delete bladder cancer, the effective filing date of the claims is the filing date of Application No. 61,266,134, i.e. 12/2/2009.
Rejections Withdrawn
7. The rejection of claims 2, 6-12, 14-15 and 17-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of applicant’s persuasive arguments.
Rejections Maintained
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 2, 6-12, 14-15, 17-20 and new claims 21-22 remain/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 new matter rejection.
The new limitations “a glycine for a residue corresponding to position 253 as numbered according to SEQ ID NO: 10”, “a glycine for a residue corresponding to position 240 as numbered according to SEQ ID NO: 12”, “a glycine for a residue corresponding to position 243 as numbered according to SEQ ID NO:13”, “a glycine for a residue corresponding to position 120 as numbered according to SEQ ID NO: 14”, and “a glycine for a residue corresponding to position 120 as numbered according to SEQ ID NO:15” are considered new matter since the specification, drawings and claims as filed do not provide clear support for these limitations.
Applicant pointed to the following paragraphs [0001], [0007], [0022], [0023], [0024], [0049], [0052]-[0053], [0055], [0077], [0093], [0095], [0096], and Figs. 3, 4, 6-9 for support.
Paragraphs which are related to “a glycine for a residue corresponding to position…” have been carefully reviewed.
Paragraph [0022] is a description of Fig. 2. Fig 2 is a comparison between the amino acid sequences of deimmunized (SEQ ID NO:5; SEQ ID NO:19), murine (SEQ ID NO:4; SEQ ID NO:18) and human Composite (SEQ ID NO:3; SEQ ID NO:17) J591 V regions. In Fig. 2, SEQ ID NO:5 and SEQ ID NO:19 are the VH and VL amino acid sequences of a deimmunized J591 antibody, respectively. The two stars designate the two Prolines introduced by the deimmunization. SEQ ID NOs: 3 and 17 are the VH and VL amino acid sequences of a human composite J591. Compared to SEQ ID NO: 19, SEQ ID NO:17 comprise P to K and P to G substitutions.
Paragraph [0023] is description of Fig. 3. Fig. 3 is the J591 human Composite VHVL minibody nucleotide and protein sequence (SEQ ID NOs: 1 and 10, respectively). The position 253 in SEQ ID NO:10 is glycine.
Paragraph [0024] is description of Fig. 4. Fig. 4 is the J591 2P VH/VL minibody nucleotide and protein sequence (SEQ ID NOs: 2 and 11, respectively).
Figs. 6-9 disclose SEQ ID NOs: 12-15. The position 240 in SEQ ID NO:12, 243 in SEQ ID NO:13, 120 in SEQ ID NO:14 and 120 in SEQ ID NO:15 are glycine.
Paragraph [0093] and [0095] describes generation of the J591 minibody construct.
Paragraph [0096] discloses that sequence alignment between the deimmunized J591 (SEQ ID NO:5; SEQ ID NO:19) and the original murine J591 (SEQ ID NO:4; SEQ ID NO:18) revealed that the deimmunization process introduced additional Proline residues (see Figure 2). After sequence and protein modeling analysis, two changes to the protein were made to improve the flexibility and folding ability. First, two Proline residues were changed in the variable light domain (P42Q and P100A) to the residues found in the murine sequence (see Figure 2, here forth referred to as 2P). Second, substitutions were calculated for both variable regions using Human Composite (HC) Antibody technology (Antitope) that deimmunizes the sequence by avoiding potential epitopes instead of destroying epitopes (see Figure 2, here forth referred to as HC).
It appears that the specification, drawings and claims as filed only provide support for “a glycine for a residue corresponding to position…” in the context of a deimmunized J591 antibody comprising SEQ ID NO: 5 and SEQ ID NO: 19. The 2nd P to G substitution is made in SEQ ID NO:19.
Although the application as filed provides support for a minibody or cis-diabody which comprises the recited 6 CDRs and a VL of SEQ ID NO: 10, 12, 13, 14 or 15, the claims are not limited to such antibodies. The claims encompass a genus of minibodies or cis-diabodies defined by comprising 6 CDR sequences of any one of SEQ ID NO: 10 and 12-15, and a glycine for a residue corresponding to position 253, 240, 243, 120, or 120 of SEQ ID NO: 10, 12, 13, 14, or 15, respectively. The claimed antibodies may comprise framework regions which are completely different from any one of SEQ ID NO: 10 and 12-15, e.g. from different species, based on a completely unrelated germline, having different framework lengths, or having large insertions/deletions. The specification does not disclose/contemplate a glycine at specified positions of different framework regions. The amendments broaden the scope of the invention, thus introduce new matter.
Regarding new claims 21 and 22, the instant specification only discloses one specific deimmunized huJ591 antibody which comprises a VH of SEQ ID NO:5 and a VL of SEQ ID NO:19 (see [0022], [0096] and Fig. 2). However, the term “a deimmunized J591 antibody” encompasses any antibodies which are variants of huJ591 antibody and have a reduced immune property compared to huJ591 antibody. Therefore, new claims 21 and 22 broaden the scope of the invention as originally disclosed, and introduce new matter.
If applicant believes that support for the above-mentioned phrases or terms is present in the specification, claims or drawing as originally filed, applicant must, in responding to this action, point out with particularity, where such support may be found.
Applicant is required to cancel the new matter in the reply to this Office Action.
Applicant’s Arguments
The response states that claim 2 is amended to recite, among other features, "...the composition comprising a humanized anti-prostate specific membrane antigen (PSMA) minibody or a humanized anti- PSMA cys-diabody, wherein..."
The present Application discloses working examples of humanized anti-PSMA minibodies and cys-diabodies that have a glycine at the recited position in the VL. See, e.g., Specification at Example 1, FIGs. 2, 3, 6-9. Further, one of ordinary skill in the art would readily appreciate that the glycine is within the framework region of the light chain variable region, and is in the context of the 6 CDRs of J591. See, e.g., Specification at [0096], FIG. 2. The present Application also specifically identifies the position in the VL corresponding to the recited glycine residue as being relevant for de-immunizing by avoiding potential epitopes. See, e.g., Specification at [0096]. Thus, in view of the present Application, one of ordinary skill in the art can readily recognize a humanized anti-PSMA minibody or cys-diabody having the recited CDR sequences and the glycine residue at the recited residue within the VL.
Applicant reminds the Examiner that description of a representative number of species for a claimed genus "does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces." M.P.E.P. j 2163 JJ.A.3.(a)ii). Rather, 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," 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." Id. Here, the-9-
Specification discloses multiple humanized anti-PSMA constructs, detailed sequence modifications, and the rationale underlying the positional glycine, as discussed above. These disclosures collectively exemplify the common structural features and functional attributes of the genus of humanized anti-PSMA minibodies and cys-diabodies as recited in the claim. At least for these reasons, Applicant submits that one of ordinary skill in the art can reasonably conclude based on the present Application that the inventors had possession of the claimed methods, including the recited minibodies and cys-diabodies, at the time of filing of the Application.
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive. The instant rejection is a new matter rejection. As discussed above in the rejection, the specification, drawings and claims as filed only provide support for “a glycine for a residue corresponding to position…” in the context of a deimmunized J591 antibody comprising SEQ ID NO: 5 and SEQ ID NO: 19. The 2nd P to G substitution is made in SEQ ID NO:19.
Although the application as filed provides support for a minibody or cis-diabody which comprises the recited 6 CDRs and a VL of SEQ ID NO: 10, 12, 13, 14 or 15, the claims are not limited to such antibodies. The claims encompass a genus of minibodies or cis-diabodies defined by comprising 6 CDR sequences of any one of SEQ ID NO: 10 and 12-15, and a glycine for a residue corresponding to position 253, 240, 243, 120, or 120 of SEQ ID NO: 10, 12, 13, 14, or 15, respectively. The claimed antibodies may comprise framework regions which are completely different from any one of SEQ ID NO: 10 and 12-15, e.g. from different species, based on a completely unrelated germline, having different framework lengths, or having large insertions/deletions. The specification does not disclose/contemplate a glycine at specified positions of different framework regions. Thus the amendments broaden the scope of the invention as originally disclosed and introduce new matter.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
10. 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.
11. Claims 21 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 recites “wherein the VL”. Claim 22 recites “wherein the VH”. Claims 21 and 22 depend directly or ultimately from claim 2. Claim 2 mentions multiple VL and VH. It is unclear which VL and VH they are in reference to.
Conclusion
12. Claims 2, 6-12, 14-15 and 17-22 are rejected. Claims 3, 4 and 16 are objected to as being dependent from a rejected claim.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HONG SANG/Primary Examiner, Art Unit 1646