DETAILED ACTION
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 .
2. The amendments and remarks filed 06/12/2026 are acknowledged. Claims 83, 84, 88 and 102 are amended. Claim 86 is cancelled. Claim 103 is new. Claims 83-85, 87-88, 92, and 102-103 are pending and under examination.
Withdrawn Rejections
3. The rejection of claims 83, 86-88, and 102 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of the Applicant’s amendments thereto. See pages 13-14 of the previous office action.
4. The rejection of claim 83, and 87-88 under 35 U.S.C 102(a)(2) for being anticipated by Gantier, et al. (US 2004/0132977 A1), is withdrawn in light of Applicant’s amendments thereto. See pages 14-19 of the previous office action.
New Rejections Necessitated by Applicant’s Amendment
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.
Written Description
5. Claims 83, 84, 85, 87, 88, 92, 102, and 103 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
The instant claims are drawn to a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, wherein the recombinant GM-CSF protein comprises the amino acid sequence having at least 98% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37 and/or T39 or a position corresponding thereto and wherein the recombinant GM-CSF protein has 10% or less hypermannosylated GM-CSF forms.
The specification discloses a recombinant human GM-CSF comprising SEQ ID NO:1 and SEQ ID NO: 2. The specification discloses a GM-CSF mutant comprising a T39A substitution, a GM-CSF mutant comprising a N37Q mutation, and Leukine, which refers to WT GM-CSF of SEQ ID NO: 1, without either of T39A or N37Q amino acid substitutions. The specification teaches that the single mutants and LEUKINE have similar bioactivity and these substitutions do not affect biological activity. The specification teaches that mutant rhuGM-CSF with a single amino acid at position N37 grown in CHO cells significantly enhanced activity. The specification teach that the mutants have a specific glycoform profile, and specifically teaches that the mutants are substantially free of hypermannosylated forms when purified without organic solvents.
The specification only discloses three species, however, the claims are not limited to these three species. The claims encompass a vast genus of compositions comprising mutants that share 98% sequence identity to SEQ ID NO: 1 or 2 and include a substitution or deletion at position N37 and/or T39. The substitutions are not limited to a particular amino acid, and thus, the claimed positions may be substitution with any of the 20 naturally occurring amino acids. Further increasing the breadth of the genus is the fact that the mutant shares 98% identity to the sequences of SEQ ID NO: 1 and SEQ ID NO: 2. A 2% variance in the 144 amino acid sequence set forth in SEQ ID NO: 1 translates into 2 residues that may be added, deleted, substituted, or otherwise mutated anywhere throughout the entire length of the amino acid sequence. To give an idea of the breadth of the claims, there are an almost unfathomable number of ways which 1 to 2 amino acids (i.e., the sum of results for 1 change, 2 changes) can be selected from the 144 residues, and without any other limitation in the independent claims, each particular residue can be substituted with any of the other 19 naturally occurring amino acids and still meet the limitation. For example, for just 1 change, there would be 144 unique sequences, but because the change at each residue can be substituted with any one of the other 19 naturally occurring amino acids, then the actual number of unique sequences encompassed is 2,736 (i.e. a sequence having a substitution at, for example residue 33 with cysteine, would be structurally distinct from a sequence having a substitution at residue 33 with tryptophan; and 144*19=2,736). Yet, the claims allow for up to 2 unrestricted changes, anywhere along the length of SEQ ID NO: 1, so with the order of selection not important and repetition not allowed, the equation is X = 19* [n!/(r!(n -r)!)], which for 2 changes, results in a number having more than 40 zeros (i.e. a trillion only has 12 zeros). As a result, there are potentially trillions of variant permutations that could be made and still maintain a variance of 0-2 amino acid substitutions. It should be noted that this example is for the mutants sharing 98% sequence identity to SEQ ID NO:1, and consideration of the other substitutions (i.e., N37 and T39) of the GM-CSF polypeptide would exponentially increase the breadth of the claims. The mutants have specific required functions. The mutants must maintain the biological activity of GM-CSF and the composition must have less than 10% hypermannosylated GM-CSF forms. However, with the exception of the GM-CSF mutant comprising the T39A substitution, GM-CSF mutants comprising the N37Q substitution, and the Leukine mutant comprising T39A and N37Q deletions, the specification provides no guidance regarding any GM-CSF mutant having the claimed functions. Therefore, these GM-CSF mutants are claimed only by their functional characteristics and the specification fails to provide a sufficient correlation between the claimed function characteristics (i.e., having GM-CSF activity and less than 10% hypermannosylation) and the necessary structural components (i.e., critical domain within the sequence).
Accordingly, the specification does not define any structural features commonly possessed by the members of the genus, because, while the description of an ability of the claimed protein may generically describe the protein’s function, it does not describe the protein itself. A definition by function does not suffice to define the genu because it is only an indication of what the protein does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves the result. In addition, because the genus of GM-CSF protein is highly variable (i.e., each complex would necessarily have a unique structure, See MPEP 2434), the generic description of the heterodimer is insufficient to describe the genus. Further, given the highly diverse nature of proteins, even one of skill in the art cannot envision the structure of the GM-CSF protein only by knowing its functional characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of GM-CSF protein claimed only by a functional characteristic and/or partial structure.
A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not sufficient identifying characteristics for written description purposes, even when accompanied by a method of obtaining the agent. The specification does not adequately describe the correlation between the chemical structure and function of the genus, such as structural domains or motifs that are essential and distinguish members of the genus from those excluded. Thus, the genus of protein has no correlation between their structure and function.
Furthermore, Applicants have not shown possession of a representative number of species that have the claimed function(s). Although the specification sets forth a correlation between the GM-CSF mutant comprising the T39A substitution, GM-CSF mutant comprising the N37Q substitution, and the Leukine mutant comprising T39A and N37Q deletions, and the required functions, the claims are not limited to these disclosed species. As noted above, the claims broadly encompass mutants that share 98% sequence identity with SEQ ID NO: 1 and SEQ ID NO: 2 and comprising T39 and/or N37 deletions or substitutions. Thus, the genus has substantial variation because of the numerous alternatives and combinations permitted. There is no description of the structure common to the members of the genus such that one of skill in the art can visualize or recognize the members of the genus. Therefore, only a single species has been described and this is not considered to be representative of the breadth of the genus.
MPEP §2163 states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number to adequately describe a broad genus. The courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus (e.g., see In re Gostelli, 872, F. 2d at 1012, 10 USPQ2d at 1618).
Further, the disclosure of only one or two 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 genu[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.") (MPEP 2163). “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).
Accordingly, the specification also does not provide adequate written description to identify the broad genus of the claimed, claimed only be a function characteristic(s) and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous heterodimers had not yet been identified and thus, the specification represents little more than a wish for possession. Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of heterodimers claimed only by a partial structure and functional characteristic(s).
Vas-Cath Inc. v. Mahurkar, 19 U5PQ2d 1111, makes clear 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.)
With the exception of the GM-CSF mutant comprising the T39A substitution, GM-CSF mutant comprising the N37Q substitution, and the Leukine mutant comprising T39A and N37Q deletions, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, 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 for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481,1483, 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.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565,1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
In Ariad Pharrns., Inc. v. Eh Lilly & Co., 598 F.3d 1336,1351 (Fed. Cir. 2010), the court held that a “sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize’ the members of the genus." Ariad, 598 F.Bd at 1350. “[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” Id. Although “functional claim language can meet the written description requirement when the art has established a correlation between structure and function," "merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genu and showing that one has invented a genus and not just a species.
Furthermore, 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. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004).
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al. (Science, 1990, 247:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (column 1, page 1306). Bowie et al. further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138,1990) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252,1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Additionally, Whisstock et al. (Quarterly Reviews in Biophysics. 36(3):307-340, 2007) teach that the prediction of protein function from sequence and structure is a difficult problem (See abstract). Although many families of proteins contain homologues with the same function, homologous proteins often have different functions as the sequences progressively diverge (See page 309). Whisstock et al. teach that assigning a function to an amino acid sequence based upon similarity becomes significantly more complex as the similarity between the sequence and a putative homologue falls. Whisstock et al. teach that while it is hopeful that similar proteins will share similar functions, substitution of a single, critically placed amino acid in an active-site may be sufficient to alter a protein’s role fundamentally (See pages 321-323). Given not only the teachings of Bowie et al., Lazar et al. and Burgess et al. but also the limitations and pitfalls of assigning a function to an amino acid sequence based upon similarity as taught by Whisstock, the claimed proteins could not be predicted. Therefore, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the agent per se and thereby does not provide adequate written description support for which structural features of any given polypeptide would predictably retain their functional activities.
Accordingly, one of skill in the art would conclude that the claimed invention encompasses a plurality of polypeptides defined solely in terms of their function that may not have the biological functions recited in the claims. Based on the teachings of the instant specification and the prior art, one of skill in the art would not conclude that Applicant was in possession of the claimed genus of agents.
While “examples explicitly covering the full scope of the claim language” typically will not be required, a sufficient number of representative species must be included to “demonstrate that the patentee possessed the full scope of the [claimed] invention.” Lizardtech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the genus. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features (see, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1895 (Fed. Cir. 2004); accord Ex Parte Kubin, 2007-0819, BPAI 31 May 2007, opinion at p. 16, paragraph 1). 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).
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).
Applicants Argument’s
A) Applicant argues the claims do not generically recite a GM-CSF protein merely by functional characteristics but defined the GM-CSF protein by SEQ ID NO: 1 and 2, the percent identity and the positional substitution or deletion at N37 and T39 for claim 83 and N37Q for claim 102. The applicant argues that the claims recite a structurally defined genus.
B) Applicant argues that a person skilled in art would have understood every member of the recited genus is closely related to the expressly sequence and different by a limited number of amino acids.
C) Applicant argues that that the amendments recite distinguishing characteristics tied to the substitutions such as having 10% or less hypermannosylated GM-CSF forms. Applicants argue that the specification amino acid substitutions are taught in the specifications.
Response to arguments
Applicants’ arguments (pages 7-10, remarks received 06/12/2026) have been fully considered but are not found persuasive for the following reasons.
A) Applicant argues that the GM-CSF protein is defined by SEQ ID NO 1 and 2 and the positional substitution or deletion at N37 and T39; however, with 20 possible amino acid substitutions (including point mutations), it is possible to have 20 possible substitutions at N37 and T39, thus the genus has substantial variation because of the numerous alternatives and combinations permitted. This does not define the necessary structure that would overcome written description.
B) Applicant argues that a skilled artisan would have understood every member of the recited genus, however, with the numerous alternative and combinations, one of skill could not reasonably conclude the specific amino acids that would necessarily allow the invention to continue to perform the same function. Although claim 102 lists the N37Q position, the breadth of claim 102 allows for an additional amino acid substitution that is not defined.
C) Applicant argues that the specific substitutions are taught in the specification, however, this is not recited in claim 83. Specific substitutions, for example include the amino acid at position N37 or a position corresponding thereto is selected from glutamine (0),serine (S), threonine (T), proline (P), and cysteine (C); and/or (b) the amino acid at T39 or a position corresponding thereto is selected from alanine (A), glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V)
To overcome the rejection, Applicant may amend the claim 83 to recite “A composition comprising a recombinant human granulocyte macrophage- colony stimulating factor (GM-CSF) protein, wherein the recombinant GM-CSF protein comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37 and/or T39, wherein (a) the amino acid at position N37 or a position corresponding thereto is selected from glutamine (0),serine (S), threonine (T), proline (P), and cysteine (C); and/or (b) the amino acid at T39 or a position corresponding thereto is selected from alanine (A), glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V) and wherein the recombinant GM-CSF protein has 10% or less hypermannosylated GM-CSF form.”
Double Patenting
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 83-85, and 92 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 114, 115, 133 and 134 of copending Application No. 18854328.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite a recombinant human granulocyte macrophage colony stimulating factor protein.
Instant claim 83 directs to a composition comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, wherein the recombinant GM-CSF protein comprises the amino acid sequence having at least 98% identity with SEQ ID NO: 1 or SEQ ID NO: 2 and having a substitution or deletion at position N37 and/or T39 or a position corresponding thereto and wherein the recombinant GM-CSF protein has 10% or less hypermannosylated GM-CSF forms. The copending application teaches the same sequences with the same substitution in claims 114 and 115 and the GM-CSF exhibiting “10% or less hypermannosylated GM-CSF forms” would be an inherent property. Any properties disclosed are inherently present in the copending claims.
Instant claim 84 further limits the recombinant human (GM-CSF) protein amino sequence wherein (a) the amino acid at position N37 or a position corresponding thereto is selected from glutamine (Q),serine (S), threonine (T), proline (P), and cysteine (C); (b) the amino acid at T39 or a position corresponding thereto is selected from alanine (A), glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V), and alanine (A); or (c) the amino acid at position E38 or a position corresponding thereto is selected from alanine (A), leucine (L), isoleucine (I), methionine (M), and valine (V).
Claim 114 of copending application ‘328 direct to a composition comprising a fusion or chimeric protein comprising a recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) protein, as well as a linker and single domain antibody. Claim 115 of copending application ‘328 further limits the recombinant human GM-CSF protein amino acid sequence wherein the recombinant human GM-CSF protein comprises an amino acid sequence: having at least 97% identity to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or having at least 97% identity to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and a substitution or deletion at position asparagine (N) 37 or a position corresponding thereto, wherein the substitution is selected from glutamine (Q), serine (S), and threonine (T). Instant SEQ ID NO: 1 and 2 are 100% identical to copending application ‘328 SEQ ID NO: 1 and 2.
Copending application ‘328 SEQ ID NO: 1 is 100% match with instant SEQ ID NO: 1
RESULT 1
US-18-854-328-1
Query Match 100.0%; Score 673; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Copending application ‘328 SEQ ID NO: 2 is 100% match with instant SEQ ID NO: 2
RESULT 1
US-18-854-328-2
Query Match 100.0%; Score 672; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APARSPSPSTQPWEHVNAIQEALRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE 60
Qy 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFD 120
Qy 121 CWEPVQE 127
|||||||
Db 121 CWEPVQE 127
Instant claim 85 teach the composition of claim 83, wherein the composition binds and/or activates the granulocyte- macrophage colony stimulating factor receptor (GM-CSF-R-alpha or CSF2R), wherein the GM-CSF-R-alpha is expressed on the surface of a cell selected from a hematopoietic progenitor cell, and wherein the hematopoietic progenitor cell is an immune cell, and/or is irradiated. Copending application ‘328 teach modulating hematopoietic progenitor cells and/or stimulating survival, proliferation and activation of neutrophils, macrophages and/or dendritic cells in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 134 to the subject, wherein the subject: is undertaking or has undertaken a cancer therapy, is undertaking or has undertaken a bone marrow transplant, has been acutely exposed to myelosuppressive doses of radiation, or has a Radiation Combined Injury (RCI). This recites the limits of instant claim 85.
Instant claim 92 teach a pharmaceutical composition comprising a recombinant human GM-CSF of claim 83 and a pharmaceutically acceptable excipient or carrier. Copending application ‘328 teach a pharmaceutical composition comprising a composition of claim 114 and a pharmaceutically acceptable excipient or carrier (claim 133), which contains the recombinant human GM-CSF of instant claim 92.
Applicant’s Arguments
A) Applicant argues that incorporation of “wherein the recombinant GM-CSF protein has 10% or less hypermannosylated GM-CSF forms” into claim 83 makes the pending claims patentably distinct from the co-pending application.
Response to Arguments
Applicant’s arguments (pages 11-12, remarks received 06/12/2026) have been fully considered but are not found persuasive for the following reasons.
A) The copending application teaches the same sequences with the same substitution and the GM-CSF exhibiting “10% or less hypermannosylated GM-CSF forms” would be an inherent property. Any properties Applicant discloses are inherently present in the copending claims.
Conclusion
8. No claims are allowed
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no case, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
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, Vanessa Ford can be reached at 571-272-0857. 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.
/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
Prosecution Insights