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 the invention of Group III, drawn to a method for treating fibrotic disease, downregulating fibroblast activation pathway, and/or inhibiting fibroblast activation comprising administering a Pear1 agonist, wherein the pear1 agonist species is an anti-Pear1 antibody or variant thereof, in the reply filed on 11/04/2025 is acknowledged. The traversal is on the ground(s) that the correlation between “Pear1 gene” and “fibroblasts” and targeted regulation of Pear1 gene (such as using it agonist) is the same or corresponding technical feature that and belongs to a single general inventive concept not taught by the prior art. This is not found persuasive because, as stated in the Restriction/Election Requirement of 11/04/2025, the inventions of Groups I-VII lack unity of invention because the groups do not all share the same or corresponding technical feature. For example, the anti-Pear1 antibody across the groups of inventions does not have to be the same. The groups of inventions share the broader concept of a Pear1 agonist in general which does not make a contribution over the prior art in view of Criel et al, which makes reference to Pear1 agonists including dextran sulfate and anti-Pear1 antibodies.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3-8, 10, and 14-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/04/2025.
Claims 1, 2, and 11-13 are examined on the merits in the present Office Action.
Claim Rejections - 35 USC § 112
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 1-2 and 11-13 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 do not recite the amino acid sequences of six non-degenerate CDRs for the genus of “Pearl1 agonists” that are antibodies correlated with the functional properties of not only targeting Pear1 but also inhibiting fibroblast activation, downregulating fibroblast signaling pathways, and/or treating fibrotic disease in a subject. Further, a ‘variant’ of the claimed anti-Pear1 antibodies can include undefined amino acid mutations that can occur in the CDR and/or framework regions of the antibody. However, there is no guidance provided in the specification about which specific amino acids can be altered in the claimed anti-Pear1 antibody such that the recited functional properties are retained.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Claim 1 is broadly drawn to a method for treating fibrotic disease, downregulating fibroblast activation signaling pathway, and/or inhibiting fibroblast activation comprising administering a Pear 1 agonist, wherein the Pear1 agonist is an antibody targeting Pear1 or variant thereof (elected species) per claim 13.
The term "Pear1 agonist” within the scope of the claimed invention refers to substances capable of enhancing the activity of Pear1 gene or protein thereof; binding Pear1 protein; promoting Pear1 to inhibit signaling pathways of fibroblast activation; reducing ECM released from fibroblasts (Page 18, Ln. 8-13 of Specification). Pear1 agonists include but are not limited to small molecule compounds, miRNAs, aptamers, antibodies or antigen-binding fragments thereof; however, the specification does not disclose a representative number of species across the claimed genus which encompasses different drug classes nor does it identify any structural features shared by Pear1 agonists for a given drug class correlated with the recited functional properties. Thus, the claimed Pear1 agonists are defined by their function alone rather than the structures responsible for said function.
With respect to the elected species, it is well-known in the art that, in order to bind antigen, a conventional antibody or antigen-binding fragment must have six complementarity defining regions (CDRs) (Janeway, see selection, in particular section 3-6). Because CDRs from both VH and VL domains contribute to the antigen-binding site, it is the combination of the heavy and the light chain, and not either alone, that determines the final antigen specificity. As presently written, however, the claims do not recite the amino acid sequences of six non-degenerate CDRs for the genus of “Pearl1 agonists” that are antibodies or antigen binding fragments correlated with the functional properties of not only targeting Pear1 but also inhibiting fibroblast activation, downregulating fibroblast signaling pathways, and/or treating fibrotic disease in a subject. While Applicant has provided examples of anti-Pear1 antibodies that can inhibit fibroblast activation (see, e.g. Example 8), such disclosure does not adequately represent the structural diversity of the claimed genus of anti-Pear1 antibodies having the functional properties recited in the claims. In fact, anti-Pear1 agonistic antibodies do not appear to be well-known or established in the art for the treatment of fibrotic disease, downregulation of fibroblast signaling pathway, and/or inhibition of fibroblast activation in a subject. Without further guidance, artisans would have to engage in additional, unpredictable basic science research to identify anti-Pear1 agonist antibodies having the claimed therapeutic outcomes.
Claim 13 further recites a “variant” of the antibody targeting Pear1. The term ‘variant’ is not specifically defined within the scope of the claimed invention and can thus include amino acid mutations caused for instance by addition, deletion, substitution, or insertion that can occur in the CDR and/or framework regions of the antibody. However, there is no guidance provided in the specification about which specific amino acids can be altered in the claimed anti-Pear1 antibody such that the ability of the resulting variant to bind to Pear1 and inhibit fibroblast activation, downregulate fibroblast signaling pathways, and/or treat fibrotic disease in a subject is retained. Indeed, it is well-known that amino acid substitutions in the CDR domains of an antibody in the CDR domains can eliminate binding activity (Piche-Nicholas et al, see entire document, in particular, Abstract). The level of skill and knowledge in the art is such that one of ordinary skill would not be able to readily identify without further testing which amino acid mutations can be made in the claimed anti-Pear1 antibody such that the ability of the antibodies to bind to Pear1 and inhibit fibroblast activation, downregulate fibroblast signaling pathways, and/or treat fibrotic disease in a subject is still retained.
Therefore, the claimed genus of anti-Pear1 antibodies or variants thereof lacks adequate written description because there does not appear to be any correlation between the structure of the claimed antibodies or variants thereof and the function of binding to Pear1 and treating fibrotic disease, downregulating fibroblast signaling pathway, and/or inhibiting fibroblast activation in a subject. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti-Pear1 antibodies or variants thereof at the time the instant application was filed.
Examiner suggestion: Applicant may overcome this rejection by amending claim 1 to specifically recite the structure of a Pear1 agonist, specifically an anti-Pear1 antibody by the amino acid sequences of six non-degenerate SEQ ID NOs, paired VH and VL chains, and/or paired heavy and light chain regions. Further, Applicant may remove the term “variant thereof” or identify in the claims the specific structures (e.g. six non-degenerate CDRs) of anti-Pear1 antibody variants having the recited functional properties.
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.
(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.
Claims 1-2 and 11-13 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bruce (WO2019050460A1) as evidenced by Biswas (Biswas, A., “Understanding pulmonary fibrosis: from symptoms to treatments”. Spire Healthcare, Spire Healthcare, 01 May. 2025).
Bruce teaches the use of dextran sulfate for the treatment of fibrotic disease, including pulmonary fibrosis, idiopathic pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, bone marrow fibrosis (e.g. myelofibrosis), as well as skin and/or soft tissue scars (e.g. keloids) (Page 2, Ln. 4-6 and Ln. 11-14; Page 22, Ln. 11-25; and Page 23, Ln. 11-18). Per the instant claims, dextran sulfate is a Pear1 agonist that enhances its expression and/or activity. Pulmonary fibrosis is a type of restrictive lung disease because the scarring (fibrosis) in the lung tissue makes the lungs stiff, preventing them from expanding fully, thus making it difficult to breath as evidenced by Biswas (see entire document, in particular, pages 1-2).
Thus, Bruce meets the limitations of instant claims 1-2 and 11-13.
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 1, 2, 12, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 11-18 of co-pending Application No. 18290817 (reference application) as evidenced by Biswas (Biswas, A., “Understanding pulmonary fibrosis: from symptoms to treatments”. Spire Healthcare, Spire Healthcare, 01 May. 2025). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or are obvious variants over the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite a method for alleviating or fibrotic diseases comprising administering a pharmaceutical composition comprising a Pear1 agonist to a subject in need (co-pending claim 1), wherein a) the fibrotic disease comprises pulmonary fibrosis, liver fibrosis, cardiac fibrosis, renal fibrosis, myelofibrosis (i.e. bone marrow fibrosis), or scars in skin and/or soft tissues (co-pending claim 2); and b) the Pear1 agonist increases the expression and/or activity of Pear 1 and is FcεR1α, dextran sulfate, fucoidan, or an antibody or antigen-binding fragment thereof that specifically activates Pear1 (co-pending claim 3). Pulmonary fibrosis is a type of restrictive lung disease because the scarring (fibrosis) in the lung tissue makes the lungs stiff, preventing them from expanding fully, thus making it difficult to breath as evidenced by Biswas (see entire document, in particular, pages 1-2).
Thus, the co-pending claims meet the limitations of instant claims 1, 2, 12, and 13.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 11-18 of co-pending Application No. 18290817, as applied to claims 1, 2, 12, and 13 above, in view of Raghu et al (Raghu, Ganesh, et al. "Incidence and prevalence of idiopathic pulmonary fibrosis." American journal of respiratory and critical care medicine 174.7 (2006): 810-816.), hereinafter Raghu.
This is a provisional nonstatutory double patenting rejection.
The teachings of the co-pending claims have been discussed above and differ from the instantly claimed invention in that it is not specifically taught that the pulmonary fibrosis is idiopathic pulmonary fibrosis.
However, Raghu teaches that idiopathic pulmonary fibrosis is a progressive life-threatening disease of unknown etiology characterized by scarring of the lungs and shortness of breath. Of the over 150 recognized types of interstitial lung disease, IPF is the most common and one of the most deleterious with a prevalence of 3 to 6 cases per 100,000 persons in the United States alone and a median survival rate of 3 to 5 years (Abstract and Introduction on Page 810).
It would have been obvious to one of ordinary skill in the art to modify the method of the co-pending claims such that the pulmonary fibrosis treated by a Pear1 agonist is idiopathic pulmonary fibrosis. One of ordinary skill in the art would have been motivated do to so since idiopathic pulmonary fibrosis is the most common and one of the most deleterious interstitial lung diseases with a prevalence of 3 to 6 cases per 100,000 persons in the United States and a median survival rate of 3 to 5 years as taught by Raghu. As such, patients with idiopathic pulmonary fibrosis represent a patient population that would receive therapeutic benefit treatment with the anti-fibrotic Pear1 agonists of the co-pending claims. Therefore, one of ordinary skill in the art would reasonably expect a Pear1 agonist can be used to effectively treat idiopathic pulmonary fibrosis in a subject according to the method of the co-pending claims.
Claims 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 6-16 of co-pending Application No. 18290815 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or are obvious variants over the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite a method for preventing, alleviating, or treating adhesive diseases comprising administering a Pear1 agonist to a subject in need (co-pending claim 1), wherein the Pear1 agonist increases the expression and/or activity of Pear 1 and is FcεR1α, dextran sulfate, fucoidan, or an antibody or antigen-binding fragment thereof that specifically activates Pear1 (co-pending claims 3 and 11). The Pear1 agonist is also used to inhibit fibroblast proliferation or activation at a lesion site (co-pending claim 4).
Thus, the co-pending claim meets the limitation of instant claim 1.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIA TAYLOR whose telephone number is (571)272-6336. The examiner can normally be reached 8:30 - 5:00 M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MISOOK YU can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LIA E TAYLOR/Examiner, Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641