Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
2. Applicant's election without traverse of Group I, claims 21, 34-36, 44-49, 52 and 57-64, in the reply filed on 08 June 2026 is acknowledged. Applicant’s election of diabetic retinopathy as the species of eye disorder is also acknowledged. Election was made without traverse in the reply filed on 24 March 2026.
3. The restriction requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, and/or Claims
4. The Response filed on 08 June 2026 has been entered in full. Claims 21, 34-36, 49, 52 and 54 have been canceled without prejudice or disclaimer, and claims 65 and 66 have been added. Newly added claims 55-56 will be examined as they fit under the rubric of the elected invention. Therefore, claims 44-48 and 57-66 are pending and the subject of this Office Action.
Information Disclosure Statement
5. The information disclosure statements (IDS) submitted on 11 June 2024 and 08 June 2026 have been considered by the examiner.
Claim Objections
6. Claim 44 is objected to because of the following informalities. Claim 44 recites “administering 1-3 loading doses”, therefor the recitation of “not administering more than 3 loading doses” is redundant.
7. Claim 47 is objected to because of the following informalities. Claim 47 recites “wherein the antibody polymer conjugate comprises a) VH and VL in FIG. 64, or b) 6 CDRs within the VH and VL of FIG. 64”. However, MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Figure 64 recites a number of cancers, and Table IV at pg. 69 recites a number of tumor associated antigens, which could easily be recited in the claims, and there is no “exceptional circumstance” which requires reliance on the cancers or tumor associated antigens being presented in tabular form. Appropriate correction is required.
Claim Rejections - 35 USC § 112, 2nd Paragraph
8. 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.
9. Claims 44-48 and 57-66 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 pre-AIA the applicant regards as the invention.
10. Claim 44 is rejected as being indefinite for reciting the limitation “a last loading dose.” Since it isn’t clear if the “follow-on application” can occur after any loading dose, or after the last loading dose, the metes and bounds of the claim cannot be determined. Claim 44 is further indefinite for reciting “after a last follow-on application”. Since the claim is limited to “0-1 follow-on applications”, it is unclear what is intended by the claim, and therefore the metes and bounds cannot be determined.
11. Claim 61 recites the limitation "the phosphorylcholine-containing polymer" in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 59, from which claim 61 depends, does not recite a phosphorylcholine-containing polymer.
11. Claims 44-48 and 57-66 are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 112 (Written Description)
12. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
10. Claims 44-48, 57-63 and 65-66 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
11. The claims are drawn quite broadly to a method of treating a subject with diabetic retinopathy (DR) the method comprising: administering 1-3 loading doses of an anti-VEGF antibody polymer conjugate to a subject with DR; not administering more than 3 loading doses; and providing between 0-1 follow-on application of the anti-VEGF antibody polymer conjugate at a point in time no sooner than 8 or 12 weeks after a last loading dose or after a last follow-on application of the anti-VEGF antibody polymer conjugate, wherein the loading doses are administered to the subject on a monthly basis. The claims also recite wherein the anti-VEGF antibody polymer conjugate comprises a phosphorylcholine-containing polymer conjugated to a non-native cysteine outside a variable region of the antibody. The claims also recite a method of treating diabetic retinopathy, the method comprising: identifying a subject with diabetic retinopathy; administering a first dose of an anti-VEGF antibody polymer conjugate to the subject; administering a second dose of the anti-VEGF antibody polymer conjugate to the subject 8 weeks after the first dose; administering a third dose of the anti-VEGF antibody polymer conjugate to the subject 12 weeks after the second dose; and administering one or more subsequent doses of the anti-VEGF antibody polymer conjugate to the subject either once every 12 weeks or once every 24 weeks after the third dose Thus the claims are drawn to a large genus of anti-VEGF antibody drug conjugates that have a particular activity, particularly a long therapeutic benefit as compared to other VEGF inhibitors.
12. The specification discloses 1 anti-VEGF antibody drug conjugate that is defined by particular amino acid sequences for the heavy and light chain variable regions, and a particular structure of the polymer. This antibody drug conjugate, designated as KSI-301, is disclosed as requiring few loading doses and infrequent subsequence doses, while exhibiting a strong therapeutic benefit in wet age-related macular degeneration and retinal vein occlusion (See Example 2 at pp. 176-177; and Example 4 at pp. 182-184, for example). However, the specification does not provide sufficient written description as to the structural features of the claimed genus of anti-VEGF antibody drug conjugates, comprised of a generically recited VEGF antibody and a generically recited polymer, that have the same activity of treating diabetic retinopathy. Furthermore, while the Specification provides adequate written description for the antibody drug conjugate designated as KSI-301 and formulations thereof for intravitreal administration for the treatment of diabetic retinopathy, it does not provide adequate written description for an anti-VEGF antibody conjugate that can be administered via any route for the treatment of diabetic retinopathy.
13. A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)(Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss.).
14. The art teaches the complexity of ocular anatomy and the physiology of the retina (e.g. the retinal pigment epithelium, the nature of intraocular mass transfer, and the overriding need to maintain ocular tolerability present challenges not present with other routes for drug administration. Many of the challenges are uniquely associated with the eye as they relate to determining intraocular pharmacokinetics and maintenance of drug stability (Awwad et al. Eur J Pharm Biopharm. 153:130-149, published 2020; cited by Applicant). Moreover, Koenig et al. (U.S. Pat. No. 10,072,075; issued 11 September 2018; cited by Applicant) disclose VEGF antibodies and conjugates thereof that extend their half-life, however the half-life of the antibody conjugate in the vitreous varies considerably.
15. Consequently, in the absence of sufficient direction and guidance, the disclosure of one species of anti-VEGF antibody drug conjugate, having a defined structure for the antibody and the polymer, does not provide sufficient written description for the entire genus of VEGF antibody drug conjugates encompassed by the claims.
16. It is noted that while the claims here are directed to methods of using anti-VEGF antibody drug conjugates, rather than the anti-VEGF antibody drug conjugates themselves, the same standard applies with regard to the written description requirement. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916,926 (Fed. Cir. 2004):
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
In University of Rochester, the "claimed method depend[ed] upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment." Id. ( citation omitted). Similarly here, the claimed methods cannot be practiced without the recited activity.
17. For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species, cannot be achieved by disclosing only one or two species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph.
18. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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 structure of the encompassed genus of 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 compound 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.
19. One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
20. Therefore, only the anti-VEGF antibody drug conjugate designated as KSI-301, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph. 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).
Claim Rejections - 35 USC § 102
21. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
22. 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.
23. Claim(s) 44 and 57 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2)as being anticipated by Koenig et al. (U.S. Pat. No. 10,072,075; issued 11 September 2018; cited by Applicant).
24. Koenig et al teach a VEGF antibody drug conjugate comprising a VEGF antibody conjugated to a polymer (See Columns 1 and 12, claims 15-19), as well as methods of treating diabetic retinopathy with intravitreal injection of said antibody conjugate (See Columns 1 and 9, claims 35-39). It is noted that the language of claims 44 and 57 do not require more than 1 administration of the anti-VEGF antibody polymer, therefor Koenig et al. meets all the limitations of claims 44 and 57.
25. Claim(s) 44 and 57 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2)as being anticipated by Healy et al. (WO 2017/100470; published 15 June 2017; cited by Applicant).
26. Healy et al teach a VEGF antibody drug conjugate comprising a VEGF antibody conjugated to a polymer, as well as methods of treating diabetic retinopathy via intravitreal injection of said antibody conjugate (See claims 1-17; pg. 24[00127])). It is noted that the language of claims 44 and 57 do not require more than 1 administration of the anti-VEGF antibody polymer, therefor Koenig et al. meets all the limitations of claims 44 and 57.
Double Patenting
27. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
28. Claims 44-48 and 57-66 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No. 11,912,784. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘784 patent recite a method of treating an eye disorder, comprising administering a species of anti-VEGF antibody conjugate that is encompassed by the genus of anti-VEGF antibody conjugates recited in the instant claims. While the claims of the ‘784 patent do not recite wherein the eye disorder is diabetic retinopathy, and instead recite wherein the eye disorder is wet age-related macular degeneration, they further recite wherein the therapeutic result of the treatment includes an improved diabetic retinopathy severity score. Therefore, it would be obvious to include this patient population. Thus, the claims are overlapping in scope.
29. Claims 44-48 and 57-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12,643,958. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘958 Patent recite a method of treating an eye disorder, comprising administering a species of anti-VEGF antibody conjugate that is encompassed by the genus of anti-VEGF antibody conjugates recited in the instant claims. While the claims of the ‘958 patent do not recite wherein the eye disorder is diabetic retinopathy, and instead recite wherein the eye disorder is retinal vein occlusion, they further recite wherein the therapeutic result of the treatment includes an improved diabetic retinopathy severity score. Therefore, it would be obvious to include this patient population. Thus, the claims are overlapping in scope.
Summary
30. No claim is allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jon M. Lockard whose telephone number is (571) 272-2717. The examiner can normally be reached on Monday through Friday, 8:00 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached on (571) 272-2911. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JON M LOCKARD/
Examiner, Art Unit 1647
June 26, 2026
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