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 II in the reply filed on 05/12/2026 is acknowledged. The traversal is on the ground(s) that a lack of unity was not shown and that the method of using the protein in the process of Group II is specifically adapted for using the protein of Group I; and, therefore, Groups I and II share a special technical feature and are linked, having unity of invention. Further, there is significant overlap between Groups II and III with the search required for Group I because Group II uses and Group III produces the protein of Group I. Therefore, the search for Group I would be required for Groups II and III, and dependent claims have some correspondence between the groups, which also limits examination burden. This is not found persuasive because the protein of Group I that is used in or prepared by the methods of Groups II and III, respectively, does not make a contribution over the prior art in view of Shan Yu et al. (Abstract 5077: Canc. Res. 73(8_Suppl.):5077, April 2013, cited in the PTO-892 mailed 3/13/26) as stated in the Requirement for Unity of Invention mailed 3/13/2026. The protein of Shan et al. not only was isolated from the venom of the same snake as the instant protein (see instant claim 6), but also is a heterodimer having an alpha and beta chain (see instant claim 1), has an anti-angiogenesis effect (see instant claim 4), weighs about 30 KD (30,000 Da, see instant claim 1) and is called the same name used in the specification for the protein of claim 1, “ZK002” (see [0027]). Therefore, it reasonably appears, absent evidence to the contrary, the protein of Shan et al. is the protein of Group I and used in or made by Groups II and III, and therefore not a special technical feature for the reasons of record. As to the argument about search and examination burden, even though the search for one group might turn up some art pertinent for another, a search is directed to references which would render the invention obvious, as well as references directed to anticipation of the invention and, therefore, requires a search of relevant literature in many different areas of subject matter. Evaluation under 35 USC 112(a) also requires search and examination which are quite distinct between groups.
Claims 1, 2, 6-16 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/12/2026.
The requirement is still deemed proper and is therefore made FINAL.
Specification
All locations referred to in the specification will be in reference to paragraph numbers found in the application’s pregrant publication US 2024/0101619 A1.
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: SNAKE VENOM PROTEIN WITH ACTIVITY OF INHIBITING ANGIOGENESIS AND INFLAMMATION, AND PREPARATION METHOD THEREOF
Trade Name or Mark
The use of the term “ATKA” in [0056] , which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Drawings
The drawings are objected to because in Fig. 11, on the y -axis, part of the writing is cut off. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 3, 17 and 18 are objected to because of the following informalities: In claim 3, line 1, “1in” should be “1 in”. The grammar in claims 17 and 18 is confusing. Clarity could be added by using phrasing such as, ‘The method according to claim __,wherein in the protein with the activity of inhibiting the angiogenesis and the inflammation has a molecular weight of the α chain of 12,000 Da to 22,000 Da, and a molecular weight of the chain ß of 9,000 Da to 19,000 Da as measured through reducing SDS-PAGE.’ Note that SDS-PAGE is defined in claim 1 as sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Claim 1 also references the α and β chains of the protein. Claims 17 and 18 ultimately depend from claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claims 3-5 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.
Claims 3-5 are indefinite because they recite a method of using the protein but have no specific method step. Claims 3-5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: how the protein is used to inhibit angiogenesis and inflammation. That is, for example, are inflamed tissues or retina with unwanted angiogenesis contacted with the protein?
Claim 4 is further indefinite because it is drawn to the protein of claim 1 in a pharmaceutical composition. A composition must comprise more than one thing (see MPEP § 2106 03(I)). Otherwise, there is nothing to distinguish the composition from the protein itself.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 3-5, 17 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim(s) recite(s) the protein of claim 1, which has a chain α and β of respectively SEQ ID NO:1 and 2, and a molecular weigh under non-reducing SDS-PAGE of 25 KDa to 35 KDa. The specification identifies this as a natural protein called ZK002 ([0007] and [0027]). This judicial exception is not integrated into a practical application because the method generically recites “using” the protein for its inherent properties. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because “using” a protein is a vague and general term for well-understood, routine and conventional activity and does not amount to significantly more than the judicial exception. (see MPEP 2106.05(d)). The claims do not integrate the protein into a practical application, and “using” the protein for its inherent properties is an instruction to merely apply its intrinsic functions (see MPEP 2106.06(f)). Using the protein does not transform it (MEPE 2106.05(c)). A pharmaceutical composition comprising the protein used as in claims 4-5 likewise neither transforms the protein nor adds extra-solution activity (see MPEP 2106.05(c) and (g)).
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 3-5 and 17-18 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 are drawn to a method of using the protein of claim 1, which has angiogenesis- and inflammation-inhibiting properties. The protein, ZK002, in preclinical models of inflammation which were carrageenan-induced swelling of rat paw and collagen-induced arthritis of mouse was shown to reduced inflammation (Examples 3 and 5), and in in vitro fetal bovine serum-induced human umbilical vein endothelial cells (HUVEC) and in vivo in mouse retina and cauterized rat cornea was shown to inhibit angiogenesis (Examples 6, 7 and 10). Also, it was shown to inhibit LPS-induced mRNA and protein of certain proinflammatory cytokines and chemokines (Examples 3, 4 and 7). The claimed use is much broader, however, simply reciting a method of using the protein, which protein inhibits inflammation and angiogenesis. The disclosure does not support the genus of uses encompassed by the claims. The specification discusses the ability of ZK002 to inhibit inflammation and angiogenesis, which it was shown to do in several of in vitro and in vivo models. It inhibits inflammatory markers iNOS, IL-1β, IL-6, IL-112, IL-18 and TNFα, as shown in the figures. It reasonably appears ZK002 inhibits angiogenesis and inflammation. A method of inhibiting angiogenesis and inflammation in vitro or in vivo to cells, a tissue or organ or animal in need thereof by administering the protein of claim 1 in an effective amount meets the written description provision of 35 USC 112(a). However, the claims are directed to or encompass any use of the protein, e.g., inhibition of neuralgia or promotion of bone grafting. None of these other uses meets the written description provision of 35 USC 112(a).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), 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 [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Therefore, only a method of inhibiting angiogenesis and inflammation in a cell culture, tissue, organ or animal by administering in vitro or in vivo the protein of claim 1 in an effective amount, but not the full breadth of the claim meets the written description provision of 35 U.S.C. § 112(a). 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).
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 3-5, 17 and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheng et al. (J. Venomous Animals Toxins including Tropical Dis. 23:20, 2017) in view of Applicant’s admission in paragraphs [0007]-[0008], [0010]-[0011] and [0027].
Cheng et al. teach 3 people bitten, i.e.¸ envenomated, by Dienagkistrodon acutus. This venom necessarily comprises ZK002 as admitted by Applicant. The properties of inhibiting angiogenesis and inflammation are necessarily inherent to that protein of the venom. The venom is a pharmaceutical composition comprising a carrier and/or stabilizer.
As admitted by Applicant ([0010]-[0011]) “Further, the present disclosure also discloses a preparation method of the protein ZK002, including the following steps sequentially: (1) dissolving venom of Deinagkistrodon acutus (D. acutus) with a Tris-HCl buffer, centrifuging, and collecting a resulting supernatant;….” In [0027] it is admitted that ZK002 is a natural protein. Therefore, the venom of D. acutus comprises ZK002, i.e., the protein of claim 1, which is defined as in [0007]-[0008] as having a weight of 25,000-35,000 Da determined by non-reducing SDS-PAGE and an α and β chain weight under reducing SDS-PAGE of 12,000-22,000 Da and 9,000-19,000 Da, respectively. The admission by Applicant is not necessary for the rejection but cited only to show that the protein of instant claim 1 is from the venom of D. acutus, which was used in Cheng et al.
Claim(s) 3-5 and 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shan Yu et al. (Abstract 5077: Canc. Res. 73(8_Suppl.):5077, April 2013, cited in the PTO-892 mailed 3/13/26)
Shan Yu et al. teaches anti-angiogenic protein ZK002, isolated from the venom of the same snake, Deinagkistrodon acutus. It is a heterodimer having an alpha and beta chain and has a total molecular weight of about 30 KD. It was purified by stepwise separation in anion-exchange and cation-exchange chromatography. It was administered to mice and, therefore, necessarily was used in a pharmaceutical composition comprising an excipient or carrier. It was used in cell culture to show an anti-angiogenesis effect.
For the reasons cited above, it reasonably appears ZK002 of Shan Yu et al. is the same protein of instant claim 1, absent evidence to the contrary. Shan Yu et al. is silent with respect to the weight of the alpha and beta chains determined by reducing SDS-PAGE, but these are inherent properties of the protein.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
August 22, 2026
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