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 .
DETAILED ACTION
1. Applicant’s election of Group I (claims 1 & 5-23, all in part) without traverse in the reply filed on 4/27/26 is acknowledged.
2. Further Applicants made the following species election.
The species are as follows:
1. One specific component of plasminogen activation pathway from claim 2.
Applicant hereby elects, without traverse, plasminogen.
2. One specific tumor from claim 6.
Applicant hereby elects, without traverse, colon cancer.
4. One specific effect from claim 7.
Applicant hereby elects, without traverse, reducing tumor volume.
5. One specific plasminogen from claim 11.
Applicant hereby elects, without traverse, Glu- plasminogen.
6. One specific sequence from claim 14.
Applicant hereby elects, without traverse, SEQ ID NO: 2.
7. SEQ ID NO: 14 in claim 13 is also included as the elected sequence.
3. All the non-elected species, non-elected cancer type and the sequences of SEQ ID Nos. 6, 8, 10 & 12 are withdrawn.
4. Priority
Receipt is acknowledged of papers (foreign priority filed 8/20/20) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
5. Drawings
The drawings filed on 2/17/23 are acknowledged.
6. IDS filed 4/27/26 is acknowledged. A signed copy of the IDS is provided with this Office Action.
7. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
8. 35 U.S.C. § 112, first paragraph (Written Description)
Claims 1 & 5-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 & 5-23 are drawn to the following genus claims:
(Currently amended) A method for treating a tumor, comprising administrating to a subject suffering from a tumor an effective amount of plasminogen.
5. (Previously Presented) The method according to claim 1, wherein the tumor is a cancer.
6. (Previously Presented) The method according to claim 1, wherein the tumor is one or more selected from the group consisting of: oral cancer, esophageal cancer, gastric cancer, small intestine cancer, colon cancer, rectal cancer, lung cancer, liver cancer, hepatocellular carcinoma, pancreatic cancer, gallbladder cancer, non-small cell lung (NSCL) cancer, bronchoalveolar cell lung cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, endometrial cancer, vaginal cancer, prostate cancer, urethral cancer, penile cancer, kidney cancer, ureter cancer, renal cell cancer, renal pelvis cancer, bladder cancer, head and neck cancer, skin cancer, melanoma, mesothelioma, bone cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, glioma, pleomorphic glioblastoma, astrocytoma, Schwann cell tumor, ependymoma, medulloblastoma, meningioma, squamous cell carcinoma, and pituitary adenoma.
7. (Previously Presented) The method according to claim 1, wherein the plasminogen has one or more effects selected from the group consisting of: reducing tumor volume, improving general survival of a subject suffering from a tumor, delaying tumor progression, inhibiting the growth of tumor cells, improving the survival rate, prolonging the survival period of a subject suffering from a tumor, relieving cancer pain, inhibiting tumor angiogenesis, promoting tumor cell necrosis or apoptosis, promoting anti-tumor immune response, regulating the expression of tumor-associated antigens or the surface molecules of lymphocytes, reducing the damage of tissues and organs caused by cancer cells, and promoting the recovery of tumor-damaged tissue structures or functions.
8. (Previously Presented) The method according to claim 1, wherein the plasminogen level in blood or the plasminogen level in tumor tissue or non-tumor tissue of a subject suffering from a tumor is higher than, equal to or lower than the plasminogen level in blood or the plasminogen level in corresponding non-tumor tissue of a healthy subject.
9. (Previously Presented) The method according to claim 1, wherein the fibrin level in blood or the fibrin level in tumor tissue or non-tumor tissue of a subject suffering from a tumor is higher than, equal to or lower than the fibrin level in blood or the fibrin level in corresponding non-tumor tissue of a healthy subject.
10. (Previously Presented) The method according to claim 1, wherein the plasminogen is administered in combination with one or more selected from the group consisting of: chemotherapy, radiotherapy, surgical therapy, cell therapy and immunotherapy.
11. (Previously Presented) The method according to claim 1, wherein the plasminogen is selected from the group consisting of: Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, delta-plasminogen, and a conservatively substituted variant thereof.
12. (Previously Presented) The method according to claim 1, wherein the plasminogen is a plasminogen protein comprising a serine protease domain and/or a lysine binding domain.
13. (Previously Presented) The method according to claim 1, wherein the plasminogen comprises a plasminogen protein having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with SEQ ID NO: 14 and having proteolytic activity.
14. (Previously Presented) The method according to claim 1, wherein the plasminogen has at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with SEQ ID NO: 2, 6, 8, 10 or 12, and still has plasminogen activity.
15. (New) The method according to claim 6, wherein the tumor is colon cancer, lung cancer, or esophageal cancer.
16. (New) The method according to claim 7, wherein the plasminogen has one or more effects comprising reducing tumor volume.
17. (New) The method according to claim 7, wherein the plasminogen has one or more effects comprising relieving cancer pain.
18. (New) The method according to claim 1, wherein the plasminogen is human plasminogen.
19. (New) The method according to claim 18, wherein the tumor is a cancer.
20. (New) The method according to claim 19, where the tumor is colon cancer, lung cancer, or esophageal cancer.
21. (New) The method according to claim 19, wherein the plasminogen has one or more effects comprising reducing tumor volume.
22. (New) The method according to claim 19, wherein the plasminogen has one or more effects comprising relieving cancer pain.
23. (New) The method according to claim 21, wherein the plasminogen has one or more effects comprising relieving cancer pain.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification, however, does not provide description of a method treating a tumor, comprising administrating to a subject suffering from a tumor an effective amount of plasminogen from any source.
The specification, however, only provides description of - A method for treating a tumor, comprising administrating to a subject suffering from a tumor mass or tissue of colon cancer in mice (See Fig. 1-6) by providing an effective amount of plasminogen, wherein plasminogen comprises an amino acid sequence of at least 95% sequence identity with SEQ ID NO: 2 and has the plasminogen activity, and wherein the plasminogen comprise an amino acid sequence of at least 95% identity to SEQ ID NO: 14 and has serine protease activity.
A few more species of plasminogen in the sequences of SEQ ID No. 6, 8, 10 & 12 are also provided.
The specification does not contain any disclosure or description of the structure and function of plasminogen sequences wherein the plasminogen has at least 75%, 80%, 85%, or 90% sequence identity with SEQ ID NO: 2, 6, 8, 10, 12 or 14, and still has plasminogen activity.
The 6 species disclosed from natural plasminogen (Glu-PLG, Glu-plasminogen) -SEQ ID NO: 2 or Amino acid sequence of serine protease domain of SEQ ID NO: 14; or Amino acid sequence of LYS77-PLG (Lys-plasminogen) of SEQ ID NO: 6; or Amino acid sequence of delta-plg (delta-plasminogen) of SEQ ID NO: 8; or Amino acid sequence of Mini-plg (small plasminogen) of SEQ ID NO: 10; or Amino acid sequence of Micro-plg (micro-plasminogen) of SEQ ID NO: 12, all of varying length for example, are not representative of the genus claimed. According to MPEP 2163, to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v.Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed.Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
The scope of each genus includes many members of plasminogen with widely differing structural, chemical, and physical characteristics. Furthermore, each genus is highly variable because a significant number of structural differences between genus members exit. The specification does not describe and define any structural features and amino acid sequences commonly possessed by each genus. There is no art-recognized correlation between any structure of a plasminogen and sequences having varying sequence homology/identity of at least 75%, 80%, 85%, 90% of the elected sequences SEQ ID NO: 2/14. Those of ordinary skill in the art would not be able to identify without further testing what specific DNA sequences would encode a protein having plasminogen activity.
The genus of protein from any source or the sequences of amino acid at least 75%, 80%, 85%, 90% of the elected sequences SEQ ID NO: 2/14 that comprise these protein molecules and encoding many different proteins may be obtained with the aid of a computer by a skilled artisan. However, there is no teaching regarding which 10-25% of the sequence that can be varied and still result in a protein having plasminogen activity. An important consideration is that structure is not necessarily a reliable indicator of function. The instant specification provides no disclosure relating similarity or identity of structure to conservation of function. General knowledge in the art provides guidance to modification of some amino acids that are tolerated without losing a protein’s tertiary structure.
The genus of polypeptides and modifications required in the claimed invention is an extremely large structurally and functionally variable genus. Further, there is no description by way of examples that the plasminogen in question will be effective in controlling the tumor of one or more selected from the group consisting of: oral cancer, esophageal cancer, gastric cancer, small intestine cancer, colon cancer, rectal cancer, lung cancer, liver cancer, hepatocellular carcinoma, pancreatic cancer, gallbladder cancer, non-small cell lung (NSCL) cancer, bronchoalveolar cell lung cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, endometrial cancer, vaginal cancer, prostate cancer, urethral cancer, penile cancer, kidney cancer, ureter cancer, renal cell cancer, renal pelvis cancer, bladder cancer, head and neck cancer, skin cancer, melanoma, mesothelioma, bone cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, glioma, pleomorphic glioblastoma, astrocytoma, Schwann cell tumor, ependymoma, medulloblastoma, meningioma, squamous cell carcinoma, and pituitary adenoma.
While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures of SEQ ID NO: 2/14 (for example), with specific structures having the associated function/activity, since one could use structural homology to isolate those polypeptides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”:
(a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105). Applicants’ are respectfully directed to the problems associated EC Classification in the section “Transferring the EC Classification enzyme to Non-Enzyme Comparisons”; pages 101-102 and Fig. 2a)-b), highlighting the structural and functional heterogeneity based on EC Classification numbers; as the stereo-specificity, substrate-specificity and catalytic properties vary widely.
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity.
The claim includes a genus that can be analyzed at several levels sequentially for the purpose of focusing the issue. First, the disclosure of plasminogen of SEQ ID NO: 2/6/8/10/12/14 combined with pre-existing knowledge in the art regarding the genetic code and its redundancies would have put one in possession of the genus of plasminogen. With the aid of a computer, one of skill in the art could identify all of the nucleic acid sequences with at least 75-90% sequence identity with SEQ ID NO: 2/6/8/10/12/14. However, there is no teaching regarding which 10-25% of the amino acids can vary from SEQ ID NO: 2/6/8/10/12/14 and still result in a protein that retains plasminogen activity. Further, there is no disclosed or art-recognized correlation between any structure other than SEQ ID NO: 2/6/8/10/12/14 and plasminogen activity. An important consideration is that structure is not necessarily a reliable indicator of function. In this example, there is no disclosure relating similarity of structure to conservation of function. General knowledge in the art included the knowledge that some amino acid variations are tolerated without losing a protein’s tertiary structure. The results of amino acid substitutions have been studied so extensively that amino acids are grouped in so-called “exchange groups” of similar properties because substituting within the exchange group is expected to conserve the overall structure. For example, the expectation from replacing leucine with isoleucine would be that the protein would likely retain its tertiary structure. On the other hand, when non-exchange group members are substituted, e.g., proline for tryptophan, the expectation would be that the substitution would not likely conserve the protein’s tertiary structure. Given what is known in the art about the likely outcome of substitutions on structure, those in the art would have likely expected the applicant to have been in possession of a genus of proteins having a tertiary structure similar to elected sequence of SEQ ID NO: 2/14 although the claim is not so limited. However, conservation of structure is not necessarily a surrogate for conservation of function. In this case, there is no disclosed correlation between structure and function. There is no disclosure of the active site amino acid residues responsible for the catalytic activity. Claims are further complicated as no reference is made to any structure or proposed modification(s). While general knowledge in the art may have allowed one of skill in the art to identify other proteins expected to have the same or similar tertiary structure, in this case there is no general knowledge in the art about similar proteins to SEQ ID NO: 2/6/8/10/12/14 to suggest that general similarity of structure confers the activity. Accordingly, one of skill in the art would not accept the disclosure of SEQ ID NO: 2/6/8/10/12/14 as representative of other proteins having plasminogen activity or mutational modifications thereof. The specification, taken with the pre-existing knowledge in the art of amino acid substitution and the genetic code, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
9. 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.
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.
Claim(s) 1, 5, 6, 11, 12, 15, 18-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO1998015643A1 (Cited in the IDS filed 4/27/26).
WO1998015643A1 teaches plasminogen or fragments thereof effective in inhibiting tumor metastasis and growth, a process for preparing the fragments, and a tumor metastasis and growth inhibitor containing the fragments as the active ingredient. The fragments are obtained from the elastase-induced hydrolysis product of Lys-plasminogen obtained by treating a plasminogen with plasmin and preferably have a potent heparin-binding activity. The inhibitor is useful for clinical therapy of solid cancers typified by lung and colon cancers. See abstract. The present invention relates to a novel biologically active plasma protein fragment and a method for preparing the protein fragment. More specifically, the present invention relates to an elastomer of rice plasminogen (Lys-Plasminogen; hereinafter, sometimes referred to as "Lys-P1g."), Which is a kind of N-terminal modified plasminogen. A plasminogen fragment having an inhibitory effect on tumor metastasis and proliferation, which is preferably a fragment having a high heparin binding property, which is a digestion product, and a tumor metastasis and growth inhibitor comprising the plasminogen fragment as a main component And a method for preparing the plasminogen fragment. The elastase degradation product of Lys-P 1 g., Particularly the Lys-P 1 g. Fragment exhibiting high heparin binding, according to the present invention is represented in the fields of biochemistry and medicine, such as lung cancer and colon cancer. It is useful in the field of clinical treatment of solid cancer and the like. See, FIELD OF THE INVENTION.
As shown in Figure 1, plasminogen is restricted by elastase to three sites in the serine protease domain, including the amino acid sequence 79Tyr to Kringle 3, the Kringle 4 site, and the Kringle 5 site. Generate Each of these three sites is a lysine binding site I. Plasminogen contains five kringle moieties (kringle 1 to kringle 5) and a serine protease domain with an active center (see FIGS. 1 and 2). Figure 7 shows suppression of lung metastasis growth of Lewis lung cancer using C57BL6ZJ mice 4 is a graph showing the effect of Lys-LBS-I in a test in comparison with G1u-LBS-I. Example 7, (Preparation of human plasminogen heparin-binding fragment).
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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