RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 11/14/2025, is acknowledged.
2. Claims 1 and 4-21 are under consideration in the instant application.
3. Claims 15 and 16 are objected to because they depend from canceled claim 3.
4. The following new grounds of rejections are necessitated by the amendment filed 11/14/2025.
5. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
6. Claims 12 and 20 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention for the same reasons set forth in the previous Office Action mailed 08/14/2025.
Applicant’s arguments, filed 11/14/2025, have been fully considered, but have not been found convincing.
Applicant submits that one of ordinary skill in the art would understand how to make and use the methods of claims 12 and 20 based on the specification and what is known in the art.
Applicant disagrees that the specification does not enable treating each and every disease provided in the claim. Applicant notes, however, that each of the diseases are eosinophilic diseases of which IL-5 plays a role. As described in the background section of the current application, IL-5 is one of the cytokines involved in hematopoiesis and inflammation, with the ability to affect inflammatory diseases. By excessively driving the production, recruitment, activation, and survival of eosinophils (a type of white blood cell), IL-5 leads to the massive accumulation of eosinophils in specific tissues and the release of toxic granular proteins and inflammatory mediators, thereby causing tissue damage, chronic inflammation, and organ dysfunction. This is why blocking IL-5, with a single-domain antibody that binds IL-5, can treat IL-5-related diseases. The diseases listed in claim 20 are known to be associated with abnormal expression of IL-5 and therefore one of skill in the art would understand that treating those diseases with a single-domain antibody that binds IL-5 can help in treatment of the disease.
A person skilled in the art is well aware that the antibody therapy lies in utilizing the highly specific binding capability of antibodies to precisely recognize and bind to specific targets (typically proteins, referred to as antigens) on pathogens (such as viruses or bacteria) or abnormal cells (such as cancer cells), thereby eliminating these threats through a series of mechanisms. Specifically, the IL-5 antibody of the present invention, by virtue of its specific binding capability to IL-5, precisely recognizes and binds to IL-5 expressed on pathogens (such as viruses and bacteria) or abnormal cells (such as cancer cells). This is precisely the fundamental reason why anti-IL-5 targeted antibodies (such as commercial Mepolizumab (see, reference 1 submitted herewith: Evidence for the efficacy and safety of antiinterleukin-5 treatment in the management of refractory eosinophilic asthma) and Reslizumab) can effectively treat eosinophilic diseases (influenced by IL-5) such as those in claim 20. For example, an antibody specifically binds to IL-5 thus preventing IL-5 from further binding to receptors on the surface of eosinophils and thereby reducing the number of blood eosinophils in patients and minimizing eosinophil-mediated inflammation and tissue damage.
Applicant also asserts that reference 2 "Ken Coppieters, Torsten Dreier, Karen Silence, Hans de Haard, Marc Lauwereys, Peter Casteels, Els Beirnaert, Heidi Jonckheere, 2006 Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collagen-induced arthritis Arthritis & Rheumatology.; 54(6):1856-66," submitted herewith, teaches that VHH can be used to treat inflamed joints in a murine model of collagen-induced arthritis. Thus, reference 2 provides support that using a single domain antigen binding protein (VHH) can be used in vivo to treat arthritis, which is one of the diseases listed in claim 20.
This is not found persuasive because neither the prior art nor the instant specification shows the effect of the claimed anti-IL-5 antibodies on eosinophil activation, eosinophil proliferation or on any disease, let alone each and every disease. While Applicant discloses in specification the scientific theory underlying the claimed invention. However, the scientific theory is very general and does not render the invention predictable. The influence of a scientific theory should depend on its empirical and demonstrable aspects and not its underlying logic. Yet such empirical and demonstrable aspects of the claimed methods with the single domain anti-IL-5 antibody are lacked in the instant specification. It is not clear that the skilled artisan could predict the efficacy of the single domain anti-IL-5 antibody, encompassed by the claims. It is not clear that the effect of the single domain anti-IL-5 antibody is directly affecting the each and every disease including asthma, allergic dermatitis, eczema, arthritis, herpes, chronic primary urticaria, scleroderma, hypertrophic scars, chronic obstructive pulmonary disease, atopic dermatitis, idiopathic pulmonary fibrosis, Kawasaki disease, sickle cell disease, Graves' disease, Sjögren's syndrome, autoimmune lymphoproliferative syndrome, autoimmune hemolytic anemia, Barrett's esophagus, autoimmune uveitis, tuberculosis, and kidney disease.
The specification fails to provide empirical data to show that the claimed methods would work in vivo. On the basis of the disclosed scientific theory, applicant concludes that the scope of the anti-IL-5 VHH antibody that treat each and every disease encompassed by the claimed invention and be provided as pharmaceutical compositions to treat any disease. The ordinarily skilled artisan would find it unpredictable to distinguish between a general knowledge at the molecular level of single domain anti-IL-5 antibody.
Given the relatively incomplete understanding in correlating between the IL-5 VHH antibody and in vivo animal models to clinical treatment each and every disease involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims, the claims are not enabled. See MPEP 2164.08.
In re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are drawn to the treatment of subjects suffering from each and every disease including asthma, allergic dermatitis, eczema, arthritis, herpes, chronic primary urticaria, scleroderma, hypertrophic scars, chronic obstructive pulmonary disease, atopic dermatitis, idiopathic pulmonary fibrosis, Kawasaki disease, sickle cell disease, Graves' disease, Sjégren's syndrome, autoimmune lymphoproliferative syndrome, autoimmune hemolytic anemia, Barrett's esophagus, autoimmune uveitis, tuberculosis, and kidney disease using the single domain anti-IL-5 antibodies. No working empirical data demonstrating that the single domain anti-IL-5 antibodies would be use for the claimed treatments. The specification lacks empirical data on the in vivo efficacy of the anti-IL-5 antibody on subject including human. The experiments in the specification never successfully used the anti-IL-5 antibody to treat each and every disease including asthma, allergic dermatitis, eczema, arthritis, herpes, chronic primary urticaria, scleroderma, hypertrophic scars, chronic obstructive pulmonary disease, atopic dermatitis, idiopathic pulmonary fibrosis, Kawasaki disease, sickle cell disease, Graves' disease, Sjégren's syndrome, autoimmune lymphoproliferative syndrome, autoimmune hemolytic anemia, Barrett's esophagus, autoimmune uveitis, tuberculosis, and kidney disease.
The lack of any working examples is exacerbated because the invention is in a highly unpredictable art- asthma, allergic dermatitis, eczema, arthritis, herpes, chronic primary urticaria, scleroderma, hypertrophic scars, chronic obstructive pulmonary disease, atopic dermatitis, idiopathic pulmonary fibrosis, Kawasaki disease, sickle cell disease, Graves' disease, Sjégren's syndrome, autoimmune lymphoproliferative syndrome, autoimmune hemolytic anemia, Barrett's esophagus, autoimmune uveitis, tuberculosis, and kidney disease - and while the level of skill of in the art may be high, the state of the prior art is that it is in fact unknown and untested what are the underlying molecule and physiologic bases of the therapeutic effects of the single domain anti-IL-5 antibody, in the related diseases with anti-IL-5 antibody.
If the use disclosed is of such nature that the art is unaware of successful treatments with chemically analogous compounds, a more complete statement of how to use must be supplied.
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements...However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims.” MPEP § 2164.03.
"Substantiating evidence may be in the form of animal tests which constitute recognized screening procedures with clear relevance to utility in humans. See Ex parte Krepelka, 231 USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein." Ex parte Maas, 9 USPQ2d 1746.
6. 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.
7. Claims 1 and 4-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, 10-11, 16, 24, 26-28, and 32-36 of copending Application No. 18714248 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of `248 publication are directed to stable antibody formations comprising immunoglobulin variable domain capble of specifically binding to IL-5 has an amino acid sequence as set forth in SEQ ID NO: 8-10 that comprising claimed CDRs of SEQ ID NOs: 47-52-59.
Applicant’s arguments, filed 11/14/2025, have been fully considered, but have not been found convincing.
Applicant request that the rejection be held in abeyance until such time that the Examiner finds allowable subject matter.
The rejection is maintained for the reasons of record.
8. No claim is allowable.
9. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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December 31, 2025
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644